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thank you sir
XNPT a buy at 28 post gsk deal.
The share price has risen from 24 to 28 in anticipation but the value looks much better to me both financially and perceptionally.
Dave
Have you looked at depomed. People think they have a generic drug delivery platform but their drug delivery actually reduces the side effects. They have a once a day cipro [which will not be a big seller] and a once a day metfomin on the market which has had a slow ramp. I believe doctors think it is simply a once a day metformin. docs don't realize it has less side effects than the others.
they are expecting phase 3 data with a better formulation of gabapentin within a couple of months. they should be able to get a decent partnership
is there anything on page 37 of barron's of interest to the board
someone told me to look at it with the phrase twice a day.
Dor Biopharma Full Article in Blood orBec
A RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF
ORAL BECLOMETHASONE DIPROPIONATE AS A PREDNISONE-SPARING THERAPY
FOR GASTROINTESTINAL GRAFT-VERSUS-HOST DISEASE
David M. Hockenbery,1 Scott Cruickshank,8 Timothy C. Rodell,8
Ted Gooley,1 Friedrich Schuening,2 Scott Rowley,3 Donald David,4 Mark Brunvand,5
Brian Berryman,6 Sunil Abhyankar,7 Michelle Bouvier,1 and George B. McDonald,1
for the orBec GVHD Study Group (whose members are listed in Appendix I).
1Fred Hutchinson Cancer Research Center and University of Washington School of Medicine,
Seattle, WA
2Vanderbilt University School of Medicine, Nashville, TN
3Hackensack University Medical Center, Hackensack, NJ
4City of Hope National Medical Center, Duarte, CA
5Rocky Mountain Blood & Marrow Transplant Program, Denver, CO
6Baylor University School of Medicine, Dallas, TX
7Oncology & Hematology Associates, Kansas City, MO
8DOR BioPharma, Miami, FL
Short title: Oral BDP for intestinal GVHD
Acknowledgements: This study was supported by an Orphan Products Development Grant from
the U.S. Food and Drug Administration (FD-R 02599) and by Enteron Pharmaceuticals, Inc., a
subsidiary of DOR BioPharma, Miami, FL.
Correspondence to: David M. Hockenbery, M.D.
Clinical Research Division (D2-190)
Fred Hutchinson Cancer Research Center
1100 Fairview Avenue North
Seattle WA 98109-1024
Telephone 206 667 4611
Email dhockenb@fhcrc.org
Authors’ Responsibilities and Contributions: David M. Hockenbery entered patients into the
trial and co-wrote the manuscript; Scott Cruickshank performed statistical analyses and assisted
in the preparation of the manuscript; Timothy C. Rodell was the medical director for the trial,
Blood First Edition Paper, prepublished online January 23, 2007; DOI 10.1182/blood-2006-05-021139
Copyright © 2007 American Society of Hematology
2
assisted in the analysis, and assisted in the preparation of the manuscript; Ted Gooley performed
statistical analyses; Friedrich Schuening entered patients into the trial; Scott D. Rowley entered
patients into the trial; Donald David entered patients into the trial; Mark Brunvand, entered
patients into the trial; Brian Berryman entered patients into the trial; Sunil Abhyankar entered
patients into the trial; Michelle Bouvier collated long-term survival data; George B. McDonald
designed the research and co-wrote the manuscript. Note that 9 additional members of the OrBec
GVHD Study Group are listed as entering patients into the trial.
Conflict of Interest Disclosure: Scott Cruickshank, Timothy C Rodell, and George B
McDonald have declared a financial interest in a company whose potential product was studied
in the present work. Each of these authors is a consultant to BOR BioPharma, Inc., the sponsor
of the study. GBM has an equity position in DOR BioPharma, Inc.
3
ABSTRACT
We tested the hypothesis that oral beclomethasone dipropionate (BDP) would control
gastrointestinal graft-vs-host-disease (anorexia, vomiting, and diarrhea). Patients were
randomized to prednisone for ten days and either oral BDP 8 mg/day (N=62) or placebo (N=67)
tablets for fifty days. At Study Day-10, prednisone was rapidly tapered while continuing study
drug. On an intent-to-treat basis, the risk of GVHD-treatment failure was reduced for the BDP
group at Study Day-50 (hazard ratio 0.63, 95% CI 0.35-1.13) and at 30 days follow-up (HR 0.55,
95% CI 0.32, 0.93). Among patients eligible for prednisone taper at Study Day-10, the risk of
GVHD-treatment failure was significantly reduced at both Study Days-50 and -80 (HR 0.39 and
0.38, respectively). By day-200 post-transplant, 5 patients randomized to BDP had died,
compared to 16 deaths on placebo, a 67% reduction in the hazard of mortality (HR 0.33, p=0.03).
In 47 recipients of unrelated and HLA-mismatched stem cells, mortality at transplant day-200
was reduced by 91% in the BDP group, compared to placebo (HR 0.09, p=0.02). The survival
benefit was durable to one-year post-randomization. Oral BDP prevents relapses of
gastrointestinal GVHD following tapering of prednisone; survival is statistically significantly
better among patients receiving BDP.
4
INTRODUCTION
Gastrointestinal graft-versus-host disease (GVHD) affects up to 60% of patients after
allogeneic hematopoietic cell transplant.1 Intestinal GVHD involves release of cytokines within
the mucosa, infiltration of donor T lymphocytes, and crypt cell apoptosis.2,3 Clinical
manifestations include anorexia, nausea, vomiting, diarrhea, and, in patients with severe
involvement, fever, cholestasis, protein-losing enteropathy, and sloughing of mucosa.4-8 In
animal studies, the extent of intestinal involvement and T-cell activation in Peyer’s patches are
determinants of survival.2,9 Initial treatment is with prednisone 1-2 mg/kg/day, followed by a
prednisone tapering schedule to prevent GVHD relapses and allow recovery of the
hypothalamic-pituitary-adrenal axis.4 Another approach to GVHD treatment involves a 5-day
course of prednisolone at 2 mg/kg/day; the response after five days is prognosis-determining.10
Prednisone-related side effects are common, particularly fatal infections, weakness,
hyperglycemia, hypertension, osteopenia, and psychiatric symptoms.
We tested the hypothesis that a topically-active corticosteroid (beclomethasone
dipropionate, BDP), taken orally, allows rapid tapering of prednisone while maintaining control
of intestinal GVHD. The results show that a 50-day course of treatment with oral BDP reduces
the frequency of relapses of GVHD following accelerated withdrawal of prednisone therapy and
results in better survival at transplant day-200 and at one year post-randomization, compared to
placebo. Because of this survival benefit, we also examined outcomes from a previous
randomized trial of a shorter, 30-day course of oral BDP.11
5
METHODS
Patient selection. Patients with symptoms of GVHD were evaluated with endoscopy and
mucosal biopsy. If biopsy specimens demonstrated histologic findings of GVHD 12,13 and stool
and mucosal biopsy cultures were negative for pathogens14,15, patients were invited to participate.
Patients were excluded if diarrhea exceeded one liter/day, or if skin or liver GVHD were present.
All patients received medications for GVHD prophylaxis; patients receiving corticosteroids
within 30 days of study entry were excluded. Patients signed informed consent documents
approved by the institutional review boards of all participating institutions.
Formulation of BDP. Both immediate release tablets and enteric-coated tablets contained 1 mg
of BDP (orBec, DOR BioPharma, Miami FL). The dosing regimen was one immediate-release
and one enteric-coated tablet, taken orally four times daily (total daily dose, 8 mg BDP).
Stratification and randomization (Table 1). A blocked stratified allocation scheme was used to
balance the treatment groups within study centers. Additional stratifying variables were HLAmatched
sibling and use of cutaneous corticosteroids at baseline. Patients were randomized to
receive either BDP or identical placebo tablets in a 1:1 allocation.
6
Table 1. Characteristics of patients according to randomization assignment.
Placebo
N=67
BDP
N=62
Overall
N=129
Age at randomization
Mean (±SD) 44.5 (±13.4) 45.9 (±13.6) 45.2 (±13.5)
Median 47.0 47.0 47.0
Range 17-66 6-70 6-70
Gender
Male 41 61% 36 58% 77 60%
Female 26 39% 26 42% 52 40%
Race
White 56 84% 54 87% 110 85%
American Hispanic 7 10% 4 6% 11 9%
Asian 1 1% 3 5% 4 3%
Black 3 4% 1 2% 4 3%
Days from transplant to randomization
Mean (± SD) 45.7 (± 31.80) 48.3 (± 32.56) 47.0 (± 32.07)
Median 35.0 37.0 36.0
Range 18 to 171 18 to 190 18 to 190
Primary diagnosis
Acute Myelogenous Leukemia 22 33% 19 31% 41 32%
Acute Lymphocytic Leukemia 7 10% 9 14% 16 12%
Chronic Myelogenous Leukemia 8 12% 8 13% 16 12%
Non-Hodgkin’s Lymphoma 7 10% 6 10% 13 10%
Myelodysplastic Syndrome 6 9% 2 3% 8 6%
Multiple Myeloma 1 1% 6 10% 7 5%
Chronic Lymphocytic Leukemia 4 6% 2 3% 6 5%
Chronic Myelomonocytic Leukemia 3 5% 2 3% 5 4%
Aplastic Anemia 2 3% 1 2% 3 2%
Hodgkin’s Disease 2 3% 1 2% 3 2%
Myelofibrosis 2 3% 1 2% 3 2%
Acute Promyelocytic Leukemia 0 0% 2 3% 2 2%
Other* 3 5% 3 5% 6 5%
Risk of relapse post-transplant**
High risk 29 43% 40 65% 69 53%
Low risk 38 57% 22 35% 60 47%
Source of donor cells
Peripheral blood stem cells 62 93% 54 87% 116 90%
Bone marrow 5 7% 8 13% 13 10%
Conditioning regimen
Myeloablative 52 78% 36 58% 88 68%
Non-myeloablative 15 22% 26 42% 41 32%
Patient/donor relationship
7
Related 45 67% 43 69% 88 68%
Biological parent 2 3% 0 0% 2 2%
Sibling 43 64% 40 65% 83 64%
Other relation 0 0% 3 4% 3 2%
HLA allele match status in siblings
Matched 43 64% 39 63% 82 64%
Mismatched for 1 or more alleles 0 0% 1 2% 1 <1%
*Other primary diagnoses included (one each): biphenotypic acute leukemia, extramedullary
leukemia tumor, metastatic renal cell carcinoma, myeloproliferative syndrome, plasmacytic
leukemia, and polycythemia vera.
**Patients were considered to be at low risk of relapse following transplant if the indication for
transplant was one of these diagnoses: aplastic anemia, chronic lymphocytic leukemia, chronic
myelogenous leukemia in chronic phase, chronic myelomonocytic leukemia, acute myelogenous
leukemia in first remission, myelodysplastic syndrome, myelofibrosis, myeloproliferative
syndrome, and polycythemia vera. Patients with other diagnoses were considered to be at high
risk for relapse after transplant.
Treatment plan. Therapy consisted of study drugs plus 10 days of prednisone. The initial 16
patients were administered prednisone 2 mg/kg/day for 10 days; the remaining 113 patients
received an initial prednisone dose of 1 mg/kg/day after hypothalamic-pituitary-adrenal axis
suppression was observed at the higher dose at the time of Study Day-50 testing. In patients with
control of GVHD symptoms at Study Day-10, prednisone was tapered over 7 days (0.25 mg/kg
twice daily on Study Days-11 and -12; 0.125 mg/kg twice daily on Study Days-13 and -14;
0.0625 mg/kg twice daily on Study Days-15 and -16), after which patients were maintained on
physiologic replacement doses of prednisone (0.0625 mg/kg daily). Patients who did not
demonstrate adequate control of GVHD by Study Day-10 were considered treatment failures.
Patients received study drug for 50 days, until they met the treatment failure endpoint, or until
8
they were withdrawn from the study. Patients who were declared treatment failures had study
drug discontinued; subsequent treatment for GVHD was dictated by their physicians.
Definitions of treatment failure and efficacy end-points. Treatment failure was a worsening or
recurrence of GVHD that required additional immunosuppressive therapy. The primary efficacy
endpoint was the time to treatment failure through Study Day-50. Prospectively defined
secondary efficacy endpoints included time to treatment failure 30 days after discontinuation of
study drug and survival at day-200 post-transplant. Survival at one year post-randomization was
evaluated in a retrospective manner.
Evaluation of drug safety and adverse events. Safety assessment was based on cumulative
prednisone exposure, the incidence and degree of hypothalamic-pituitary-adrenal axis
suppression, and rates of adverse events.
Statistical methods. A total sample size of approximately 130 patients (65 in each group) with
48 treatment failure events was determined to provide 80% power for a comparison of time-totreatment-
failure between treatment groups using the log-rank test.16 The sample size calculation
was based on a two-sided significance level of 0.05 and assumed treatment failure rates at Study
Day-50 of 0.30 and 0.55 for the BDP and placebo groups, respectively. These assumptions were
predicated upon the results of a previous randomized trial of BDP in the same patient
population.11 The study was planned to enroll approximately 130 patients to compensate for loss
to follow-up for the secondary endpoints and to provide adequate safety data. Analysis of the
time-to-treatment-failure and survival endpoints includes all randomized patients. The primary
analysis of time-to-treatment-failure and survival post-randomization was based on the Kaplan-
Meier method and log-rank test, stratified by donor type (HLA-matched sibling vs. unrelated or
HLA-mismatched donor). For each endpoint, the hazard ratio for treatment was estimated based
9
on a stratified Cox proportional hazards model that included a term for treatment group.16
Because of the variable length of time among patients between transplant and randomization,
randomization to BDP treatment was defined in the proportional hazards model as a timedependent
covariate for the day-200 post-transplant survival endpoint.17 Under this model, the
comparison between BDP and placebo was made using the Wald chi-square test. For the primary
analysis, the time-to-treatment-failure was right-censored for patients who discontinued study
drug during the first 50 days without meeting the criteria for treatment failure, provided the
reason for discontinuation was not related to uncontrolled GVHD or study drug-related toxicity.
This determination was made in real time and prior to analysis by the study’s medical monitor
who was blinded to the patients’ randomly assigned treatment. For each survival endpoint, a
variety of multivariate models was used to determine if the reduced mortality risk attributed to
BDP in the univariate model was still present after accounting for subject-, disease-, and
transplant-related factors. Hypothesis tests of the primary and secondary endpoints were
performed using a two-sided significance level of 0.05. No adjustments were made to the
significance level for inferential tests of the secondary endpoints. All patients who received at
least one dose of BDP or placebo were included in the assessment of safety. In addition to the
primary analysis of the treatment failure and survival endpoints, an exploratory analysis was
performed to assess the impact of the 12 patients who experienced treatment failure shortly after
randomization (i.e., during the first 10 days of protocol treatment during which oral BDP is
unlikely to affect initial responses to concomitant high-dose corticosteroids). Patients who
experienced treatment failure during this period were right-censored at the time of early
treatment failure. Analyses were done using SAS® (version 8.2), R (version 2.0.1), and S-Plus
(version 6.2) software.18,19
10
RESULTS
Patient demographics (Table 1). Between July 2001 and July 2004, 129 patients were enrolled.
With the exception of the transplant conditioning regimen (myeloablative or non-myeloablative),
no major imbalances were noted between the treatment groups for baseline transplant-related
characteristics. The percentage of patients who received a non-myeloablative conditioning
regimen was approximately two-fold higher in the BDP group compared to placebo (Table 1).
Analysis of treatment efficacy (Figure 1). By Study Day-50, there were 30 GVHD-treatment
failures in the placebo group and 18 in the BDP group. Fourteen patients (7 in each group)
discontinued from study drug early for reasons not related to uncontrolled GVHD or study drugrelated
toxicity and were right-censored on the day of their last dose of study drug. The
cumulative rate of GVHD-treatment failure was 31% for BDP vs. 48% for placebo; the hazard of
treatment failure was reduced in the BDP group relative to placebo, although not statistically
significantly so (HR 0.63; 95% CI: 0.35, 1.13; p=0.12 stratified log-rank test) (Figure 1A).
11
Figure 1. Time to GVHD-treatment failure through Study Day-80 with hazard ratios and
confidence intervals. Panel A shows product limit estimates on an intent-to-treat basis;
panel B shows estimates with a guarantee period for the first ten days of treatment.
Estimates are based on the Kaplan-Meier method. The hazard ratios at Study Day-50 were
A) 0.63; 95% CI: 0.35, 1.13; p=0.12 and B) 0.39; 95% CI: 0.19, 0.81; p=0.009, respectively.
12
The majority of patients with GVHD treatment failure had recurrent gastrointestinal
symptoms; three patients had gastrointestinal and skin GVHD; six had skin GVHD; two had
liver GVHD; and one had bronchiolitis obliterans-organizing pneumonia. GVHD-treatment
failure occurred during the first 10 days of prednisone treatment in twelve of the 48 patients with
GVHD-treatment failure by Study Day-50 (8 BDP, 4 placebo). The impact of early treatment
failures on the primary endpoint was assessed by designating the first 10 days of treatment as a
guarantee period (see Methods). Patients with treatment failure during the guarantee period were
right-censored on the day of GVHD-treatment failure. For this analysis, the risk of GVHDtreatment
failure by Study Day-50 was statistically significantly reduced for the BDP group
relative to placebo (hazard ratio 0.39; 95% CI: 0.19, 0.81; p=0.009 stratified log-rank test)
(Figure 1B).
By Study Day-80, 30 days after discontinuation of study drug, a total of 22 patients in the
BDP group and 39 patients in the placebo group were GVHD-treatment failures. Six patients (4
BDP, 2 placebo) withdrew from study during the 30-day post-treatment observation period who
did not experience treatment failure prior to their withdrawal. Based on blinded review, the
reason for withdrawal was classified as unrelated to uncontrolled GVHD or study drug-related
toxicities. The time to treatment failure was right-censored for the 6 patients on the day of their
last study visit. The cumulative treatment failure rates were 39% for BDP and 65% for placebo.
For the entire 80-day study period, the risk of treatment failure was statistically significantly
reduced for patients in the BDP group relative to placebo (hazard ratio 0.55; 95% CI: 0.32, 0.93;
p=0.02, stratified log-rank test) (Figure 1A). In an analysis using a 10-day guarantee period, the
risk of treatment failure was statistically significantly reduced for the BDP arm relative to
13
placebo for the 80-day study period (hazard ratio 0.37; 95% CI: 0.20, 0.69; p=0.001, stratified
log-rank test) (Figure 1B).
Survival analysis at transplant day-200 (Table 2). By day-200 post-transplant, 5 patients (8%)
who had been randomized to BDP had died, compared to 16 deaths (24%) among patients who
had been randomized to placebo. Based on a stratified time-dependent Cox proportional hazards
model, the risk of mortality during the 200-day post-transplant period was 67% lower with BDP
treatment compared to placebo treatment (hazard ratio 0.33; 95% CI: 0.12, 0.89; p=0.03, Wald
chi-square test). The number of deaths (21) does not allow the inclusion into the regression
model of more than 1 or 2 variables in addition to the treatment group variable. The only factor
that was largely imbalanced between the treatment groups was the planned intensity of the
transplant conditioning regimen (Table 1). Adjustment for this factor did not, however, alter the
estimated hazard ratio for mortality for BPD treatment vs. placebo (adjusted hazard ratio 0.33,
95% CI: 0.12, 0.91; p=0.03, Wald chi-square test). Moreover, the estimated treatment effect also
remained generally unchanged after adjusting for various combinations of other factors (resulting
in models with no more than 2 factors in addition to treatment group), including study center,
patient age and gender, primary diagnosis (high relapse risk or not), source of donor cells
(marrow, peripheral blood stem cells), and donor-recipient HLA match (data not shown).
The most common proximate causes of death by transplant day-200 were relapse of the
underlying malignancy and infection (Table 2). Relapse of the hematologic malignancy had
contributed to the deaths of 9/67 patients (13.4%) in the placebo arm and 3/62 patients (4.8%) in
the BDP arm. Infection contributed to the deaths of 9/67 patients (13.4%) in the placebo arm and
3/62 (4.8%) in the BDP arm. Acute or chronic GVHD was the proximate cause of death in 3/67
patients (4.5%) in the placebo arm and in 1/62 (1.6%) in the BDP arm.
14
Table 2. Analysis of survival at transplant day-200 among patients in the current trial and
in the previous randomized, placebo-controlled trial of oral BDP.
Current trial
Previous trial11
Placebo BDP Placebo BDP
Number randomized
67
62
29
31
Number (%) who died
16 (24%)
5 (8%)
6 (21%)
3 (10%)
Hazard ratio (95% confidence interval)
0.33 (0.12, 0.89)
0.47 (0.12, 1.87)
Death with infection*
9 (13%)
3 (5%)
5 (17%)
2 (6%)
Death with relapse*
9 (13%)
3 (5%)
4 (14%)
1 (3%)
*Some patients died with both infection and relapse of their underlying malignancy.
There was a statistically significant interaction (p=0.05) between donor type (HLAmatched
sibling vs. other donors) and use of BDP for the outcome day-200 mortality, suggesting
the need for separate analyses according to donor type. Among 47 patients who had received
stem cells from unrelated or HLA-mismatched donors, 1 of 23 patients (4%) who had been
randomized to BDP had died, compared to 10 deaths (42%) among 24 patients who had been
randomized to placebo, leading to a statistically significantly reduced risk of day-200 mortality
(hazard ratio 0.09; 95% CI: 0.01, 0.70; p=0.02, Wald chi-square test). On the other hand, among
82 patients who had received stem cells from an HLA-matched sibling, 4 of 39 (10%) patients
randomized to BDP had died by day 200, compared to 6 of 43 (14%) deaths among patients
randomized to placebo, leading to a lower risk of mortality, but not statistically significantly so
(hazard ratio 0.83; 95% CI: 0.23, 2.93; p=0.77, Wald chi-square test).
15
Survival analysis at one year after randomization (Figure 2A). Of 129 patients randomized,
two were lost to follow-up within one year of randomization (last contacted at 321 and 354 days
post-randomization; both patients had been randomized to BDP); in the survival analysis these
patients were right censored on the date of last contact. All other surviving patients were
followed a minimum of one year after randomization. Overall, 28 patients (42%) in the placebo
group and 18 patients (29%) in the BDP group died within one year of randomization (hazard
ratio 0.54, 95% CI: 0.30, 0.99, p=0.04, stratified log-rank test) (Figure 2A).
16
Figure 2. Survival of patients to one year after randomization to either BDP or placebo.
A) The current patient cohort (N=129); B) Patients from the previous randomized trial
(N=60)11.
17
Safety and adverse events. The frequencies of severe adverse events, adverse events related to
study drug, and adverse events resulting in study drug discontinuation were all higher in the
placebo group. Patients who remained on BDP until Study Day-50 had a higher likelihood of
having biochemical evidence of abnormal HPA function compared to patients on placebo.
Survival analysis of patients in a previous randomized trial of oral BDP.11 This trial enrolled
60 patients, 31 randomized to oral BDP and 29 to placebo. The duration of treatment with study
drug was 30 days, with a ten-day follow-up period. The treatment response rate at Study Day-30
was 71% for BDP vs. 41% for placebo (p=0.02).11 Analysis of survival at day-200 posttransplant
is shown in Table 2. Three patients (10%) who had been randomized to BDP had died,
compared to 6 deaths (21%) among patients who had been randomized to placebo, leading to a
reduced hazard of day-200 mortality, although not statistically significantly different. By
transplant day-200, relapse of hematologic malignancy had contributed to the deaths of 4/29
patients (14%) in the placebo arm and 1/31 patients (3%) in the BDP arm. Infection contributed
to the deaths of 5/29 patients (17%) in the placebo arm and 2/31 (6%) in the BDP arm. By one
year after randomization, 9 of 29 patients in the placebo group and 6 of 31 patients in the BDP
group had died (Figure 2B).
Long-term survival. As of September 1, 2005, median follow-up of patients in the two
randomized trials of BDP was 3.5 and 3.6 years for patients in placebo and BDP groups,
respectively, with an overall range of 10.6 months to 11.1 years. The risk of mortality was 37%
lower for patients randomized to BDP compared to placebo (hazard ratio 0.63, p=0.03, stratified
log-rank test).
18
DISCUSSION
This placebo-controlled trial demonstrates that oral BDP allows prednisone to be rapidly
tapered with fewer recurrences of GVHD. Although the endpoint time-to-treatment failure by
Study Day-50 did not reach statistical significance, the outcome of all clinically-important
secondary endpoints, including Study Day-80 efficacy, day-200 survival, and survival at one
year after randomization) were statistically significantly better in the BDP group. These results
confirm those of a smaller, single-center, placebo-controlled trial of BDP.11 In patients who had
been randomized to BDP in the current trial, there were reductions in the hazard of mortality of
66% and 46% at day-200 and at one year after randomization, respectively. The earlier, sixtypatient
randomized trial11 showed similar reductions in the hazard of mortality. The current trial
was undertaken to extend BDP treatment from 30 days to 50 days and to demonstrate efficacy in
centers with disparate practices. In an analysis of patients in the current study who had received
cells from unrelated or HLA-mismatched donors, the reduction in the hazard of mortality at day-
200 was 91% among patients randomized to BDP, compared to placebo. Patients with abdominal
pain, secretory diarrhea in excess of one liter daily, intestinal bleeding, or liver and skin GVHD
were not included in this study, as patients who were more likely to develop severe GVHD were
not optimal candidates for a strategy that attempted to minimize prednisone exposure.5,10,20-22
The patients enrolled are representative of most patients now presenting with acute GVHD, as
more severe GVHD has become less common than in the past.1,23
The beneficial effects of topical corticosteroids for mucosal inflammatory
diseases of the intestinal tract, lungs, and nasopharynx have been known for over 30 years.24-27
Exacerbations of asthma, chronic obstructive pulmonary disease, and Crohn’s disease respond to
high-dose prednisone therapy, but maintenance therapy is often accomplished with topical
19
corticosteroids.28,29 Because GVHD involves the mucosa from the stomach to the rectum,
formulations of oral BDP were composed of an immediate-release tablet, bioavailable to gastric,
duodenal, and jejunal mucosa, and an enteric-coated tablet, for jejunal, ileal, and colonic
mucosa.30,31 Oral BDP is biologically active as an immunosuppressive drug in vivo32; the parent
compound is metabolized in intestinal mucosa and the liver to beclomethasone-17-
monopropionate (17-BMP), which has ~25-fold greater glucocorticoid receptor binding activity
than BDP.33 BDP does not appear in the systemic circulation because of its metabolism in
intestinal mucosa and the liver, but 17-BMP can be detected in the blood stream.34 It is believed
that the primary anti-inflammatory effect of oral BDP occurs in the gastrointestinal mucosa as
both BDP and 17-BMP are present in high concentrations there. Compared to prolonged
prednisone exposure to control GVHD, any systemic effect of BMP in predisposing patients to
infection must be relatively minor, as patients randomized to BDP had infrequent fatal infections
and better day-200 post-transplant survival.
A treatment that controls the signs and symptoms of GVHD while avoiding prolonged
systemic immunosuppression is likely to result in fewer serious infections. High-dose
glucocorticoids decrease immune responses to CMV35 and increase the risk of uncontrolled
CMV viremia during antiviral therapy36; increase the risk of invasive aspergillosis and mold
infection-related death after HCT with non-myeloablative conditioning regimens37,38 and greatly
increase the risk of blood stream infections following reduced intensity cord blood transplants.39
We speculate that the frequency of leukemic relapse may be higher in the placebo arm because
protracted exposure to prednisone to control symptoms of GVHD abrogates T-cell responses;
however, the study was not designed to address this question.
20
Other potential mechanisms by which a highly potent topical corticosteroid might
improve outcomes are blunting of inflammatory cytokine production by T cells in intestinal
mucosa, inhibition of T cell-mediated apoptosis of epithelial cells, induction of apoptosis in
activated effector T cells, and deviation of T cells responses toward tolerance or nonresponsiveness.
Several studies have shown that glucocorticoids inhibit the differentiation40 and
maturation41 of dendritic cells in vitro. These effects might help to preserve integrity of the
mucosal surface, thereby reducing activation of innate immune mechanisms.
With the exception of adrenal axis suppression, we could not identify adverse reactions to
oral BDP in the current study, or in prior studies that specifically examined infection as an
adverse event.11,31 The use of BDP inhalers has been associated with oropharyngeal and
esophageal candidiasis42,43, but oral delivery of BDP did not result in an increased incidence of
fungal or bacterial colonization or infections after hematopoietic cell transplant.11,31 Metabolites
of BDP are systemically bioavailable, resulting in decreased adrenal responsiveness over time of
drug exposure.31,44-47 Two recent studies of long-term use of oral, topically-active corticosteroids
in doses similar to those used in this trial demonstrated little evidence of clinical adrenal
insufficiency.45,48
Two randomized trials have shown that oral BDP prevents relapses of acute
gastrointestinal GVHD after accelerated withdrawal of prednisone therapy. The effect is durable
even following discontinuation of BDP. We hypothesize that topical therapy with BDP improved
survival by limiting GVHD-related gastrointestinal epithelial injury, preserving the mucosal
barrier, reducing the need for systemic glucocorticoid treatment, and reducing the frequency of
life-threatening infections. The duration of the survival benefit in patients randomized to BDP,
however, will require longer follow-up.
21
REFERENCES
1. Martin PJ, McDonald GB, Sanders JE, et al. Increasingly frequent diagnosis of acute
graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biology of Blood
and Marrow Transplantation. 2004;10:320-327.
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DOR BioPharma Raises $5.5 Million in Private Equity Financing
Friday February 9, 8:01 am ET
near market no warrants. Everyone must admit, very unusual for a penny stock. There must be something to this orbec
MIAMI, FL--(MARKET WIRE)--Feb 9, 2007 -- DOR BioPharma, Inc. ("DOR" or the "Company") (OTC BB:DORB.OB - News) announced that it has completed the sale of common stock in a private placement to institutional investors as well as members of DOR's senior management and Board of Directors. DOR received gross proceeds of approximately $5.5 million.
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Under the terms of the financing, DOR will issue 11,680,851 shares of common stock at $0.47 per share representing a 6% discount to yesterday's close, subject to customary closing conditions.
"The New Year is off to an exciting start for DOR and its shareholders," stated Christopher J. Schaber, Ph.D., President and Chief Executive Officer of DOR. "This financing was completed at near market price and without the issuance of any warrants demonstrating a strong vote of confidence by highly regarded investors. With a significantly strengthened balance sheet, we will be able to focus on obtaining regulatory approval of orBec®, while continuing to explore all potential strategic and partnering options from a position of strength. We look forward to building on our recent achievements and expect 2007 to be an eventful year."
The Company plans to use the proceeds from the financing for (i) continuation of regulatory interaction with the US Food and Drug Administration ("FDA") and the European Medicines Evaluation Agency ("EMEA") for orBec® (oral beclomethasone dipropionate), including the upcoming FDA Oncology Drugs Advisory Committee ("ODAC") meeting; (ii) market research activities to position orBec® for potential commercial launch; (iii) initiation of a Phase 2 clinical trial of orBec® for the new indication of prevention of GI GVHD; (iv) further clinical and preclinical development of its pipeline products, including its Lipid Polymer Micelle ("LPM") technology and biodefense vaccine development programs for ricin and botulinum toxins; and (vi) general corporate purposes.
The Company's common stock was sold to accredited investors in the private placement in reliance on an exemption from the registration requirements of the Securities Act of 1933, as amended (the "Securities Act"). The shares have not been registered under the Securities Act or any state securities laws, and the shares may not be offered or sold absent registration or an applicable exemption from the registration requirements of the Securities Act and applicable state securities laws. In connection with the offering, DOR has agreed to file a registration statement under the Securities Act covering the resale of the shares purchased within 30 days. This press release does not and will not constitute an offer to sell or the solicitation of an offer to buy shares and is being issued under Rule 135c under the Securities Act.
About DOR BioPharma, Inc.
DOR BioPharma, Inc. is a biopharmaceutical company developing products to treat life-threatening side effects of cancer treatments and serious gastrointestinal diseases, and vaccines for certain bioterrorism agents. DOR's lead product, orBec® (oral beclomethasone dipropionate), is a potent, locally acting corticosteroid being developed for the treatment of GI GVHD, a common and potentially life-threatening complication of bone marrow transplantation. DOR has filed an NDA with the FDA for the treatment of GI GVHD, and has received a PDUFA date of July 21, 2007. In addition, the FDA's Oncology Drug Advisory Committee ("ODAC") will review the NDA for orBec® on May 9, 2007. An MAA with the EMEA for orBec® has also been filed and validated. orBec® may also have application in treating other gastrointestinal disorders characterized by severe inflammation.
Through its Biodefense Division, DOR is developing biomedical countermeasures pursuant to the recently enacted Project BioShield Act of 2004. DOR's biodefense products in development are recombinant subunit vaccines designed to protect against the lethal effects of exposure to ricin toxin and botulinum toxin. DOR's ricin toxin vaccine, RiVax(TM), has been shown to be safely tolerated and immunogenic in a Phase 1 clinical trial in normal volunteers.
For further information regarding DOR BioPharma, please visit the Company's website located at www.dorbiopharma.com.
This press release contains forward-looking statements, within the meaning of Section 21E of the Securities Exchange Act of 1934, that reflect DOR BioPharma, Inc.'s current expectations about its future results, performance, prospects and opportunities, including statements regarding the potential use of orBec® for the treatment of gastrointestinal GVHD and the prospects for regulatory filings for orBec®. Where possible, DOR has tried to identify these forward-looking statements by using words such as "anticipates," "believes," "intends," or similar expressions. These statements are subject to a number of risks, uncertainties and other factors that could cause actual events or results in future periods to differ materially from what is expressed in, or implied by, these statements. DOR cannot assure you that it will be able to successfully develop or commercialize products based on its technology, including orBec®, particularly in light of the significant uncertainty inherent in developing vaccines against bioterror threats, manufacturing and conducting preclinical and clinical trials of vaccines, and obtaining regulatory approvals, that its technologies will prove to be safe and effective, that its cash expenditures will not exceed projected levels, that it will be able to obtain future financing or funds when needed, that product development and commercialization efforts will not be reduced or discontinued due to difficulties or delays in clinical trials or due to lack of progress or positive results from research and development efforts, that it will be able to successfully obtain any further grants and awards, maintain its existing grants which are subject to performance, enter into any biodefense procurement contracts with the U.S. Government or other countries, that the U.S. Congress may not pass any legislation that would provide additional funding for the Project BioShield program, that it will be able to patent, register or protect its technology from challenge and products from competition or maintain or expand its license agreements with its current licensors, or that its business strategy will be successful. Important factors which may affect the future use of orBec® for gastrointestinal GVHD include the risks that: because orBec® did not achieve statistical significance in its primary endpoint in the pivotal Phase III clinical study (i.e. a p-value of less than or equal to 0.05), the FDA may not consider orBec® approvable based upon existing studies, orBec® may not show therapeutic effect or an acceptable safety profile in future clinical trials, if required, or could take a significantly longer time to gain regulatory approval than DOR expects or may never gain approval; DOR is dependent on the expertise, effort, priorities and contractual obligations of third parties in the clinical trials, manufacturing, marketing, sales and distribution of its products; or orBec® may not gain market acceptance; and others may develop technologies or products superior to orBec®. These and other factors are described from time to time in filings with the Securities and Exchange Commission, including, but not limited to, DOR's most recent reports on Form 10-QSB and Form 10-KSB. DOR assumes no obligation to update or revise any forward-looking statements as a result of new information, future events, and changes in circumstances or for any other reason.
Contact:
Company Contact:
Evan Myrianthopoulo
Chief Financial Officer
(786) 425-3848
http://www.dorbiopharma.com
Investor Contacts:
Lippert/Heilshorn & Associates
Anne Marie Fields
Email Contact
(212) 838-3777
Bruce Voss
Email Contact
(310) 691-7100
--------------------------------------------------------------------------------
Source: DOR BioPharma, Inc.
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Dew re MCU SPA. I was shooting from the hip there. I don't know the percentage of fast tracked drugs with a pivotal trial SPA actually become approved. Please advise.
Perhaps I was thinking wishfully.
Thanks,
every case stands on its own. fast trak doesn't matter. the best chance of success requires a safe drug meeting the primary endpoint
Stock (ticker): ChemGenex (CXS.AX)
Market Cap: A$97m
Recommendation: Buy
Share price: A$0.66
Price target: A$0.91
Up/(down) to target: 38%
Fair value: A$1.40 (DCF methodology)
Subject: CXS - Respected players invest in CXS - Viewed as positive
Analyst: Scott Power (+61 7 3334 4884) / Tanya Solomon (+61 7 3334 4521)
Key points:
* Sell down - Charter Pacific (CHF.AX) has sold down it stake (28.1m shares or ~18.5%) in CXS today at a price of A$0.62 per share. Charter Pacific appointed CXS directors Kevin Dart and Roger Byrne have also stepped down from the CXS board. These shares were acquired by respected biotechnology investment firms GBS Venture Partners (Melbourne based), Alta Partners (San Fransico based) and domestic institutions.
* Placement - Following this, CXS has completed a capital raising of A$10.5m through an institutional share and option placement. The new 17.1m shares will be issued at 62cps and the attaching 5.6m options (at 1 for 3) will have a 5 year term and A$0.75 exercise price. This investment was again led by GBS Venture Partners, Alta Partners and domestic institutions.
* Rights issue - To allow existing investors to participate, a 1:10 rights issue for shares and options at the same terms as the placement will be conducted. While the details of this have not yet been released, both Alta Partners and GBS Venture Partners have indicated their intention to participate. If fully subscribed this will raise an additional A$10.5m.
* New directors - CXS has appointed to new non executive directors - Mr Daniel Janney (Alta Partners) and Dr Geoff Brooke (GBS Ventures).
* Investment view - We view these events as positive. CXS is now well funded and following this capital raising and rights issue will have approximately A$25m in cash. CXS is now able to accelerate the development of the remainder of its pipeline, in particular its lead compound Ceflatonin to treat other forms of leukaemia.
* About Alta Partners - Alta Partners is recognised as one of the leading venture capitalist companies in the US with ~US$2b under management. Since its inception it has invested US$1b in more than 125 companies. http://altapartners.com/
Additional details:
* CXS lead compound is Ceflatonin. It is being developed to treat a particular group of patients with Chronic Myeloid Leukaemia who have developed resistance to the current treatments (T315i mutation). Currently in registration directed clinical trials, it is expected that these will be completed in 2HCY07.
* Quinamed is CXS' second clinical stage program. It has shown efficacy in prostate, ovarian and breast cancers. Currently in a Phase 2a clinical trial, if all goes to plan, a Phase 2b trial is expected to commence in 2HCY07.
Key upcoming milestones
* Ceflatonin - Preliminary data from on-going registration directed clinical trials in 4QCY06 - Achieved
* Quinamed - Phase 2a clinical trial to be completed by end CY06 with results expected in 1QCY07
* Ceflatonin - Complete enrolment for registration directed trials in 2HCY07
* Quinamed - Initiation of Phase 2b clinical trial in 2HCY07.
Overall, we consider CXS to be a Tier 1 life science company for three reasons:
* Advanced, deep pipeline means plenty of newsflow - CXS has an advanced pipeline with its lead product to treat a type of leukaemia, called Chronic Myeloid Leukaemia, expected to reach the market in CY08. This is backed up by products to treat cancer, depression, anxiety and metabolic diseases. The depth of the pipeline means multiple newsflow opportunities.
* Well funded - We believe that on completion of the placement and rights issue, CXS should have sufficient cash to take it to the market launch of Ceflatonin.
* Undervalued compared to peers - It is worth noting that CXS' pipeline is particularly advanced in comparison to its Australian peers. Additionally, compared with other listed life-science companies with compounds in late stage development, CXS is undervalued.
* We remain comfortable with our Buy recommendation and A$0.91 price target and expect the stock to be re-rated as trial results are announced.
DISCLOSURE - ABN AMRO Morgans acted as Adviser and Lead Manager to CXS in relation to the placement and was engaged by Charter Pacific to manage the sale of its 28.1m shares. ABN AMRO Morgans acted as corporate adviser and Lead Manager to a placement of shares by ChemGenex Pharmaceuticals in May 2006 and will earn fees in this regard. The Analyst owns shares.
Tanya Solomon | Analyst | Authorised Representative 282999
ABN AMRO Morgans Limited | ABN 49 010 669 726 | AFSL 235410
Level 29, Riverside Centre, 123 Eagle Street, Brisbane, Qld 4000
( Ph +61 7 3334 4521 | 7 Fax +61 7 3834 0521 | + tsolomon@abnamromorgans.com.au
P Please consider the environment before printing this email
Thanks RFJ I was aware of the 467,000 in 2003 and the trend toward 5% decline. The huge drop in 2004 was news to me. I would have thought that the recent problems with coated stents etc. would have meant a slow down in the drop. Thanks for the input.
Dave
[as you say the drug eluting stent problems are recent and will slow down their use. Cabg will be used more
Reward target for MCU market size & forecast.
I'll throw out targets for all to throw stones at and discount down to the present market value.
Assumptions: Headline endpoint data will be available in April 2009 or B4. MCU files in June 09 or B4. It's an approved drug Jan 2010 or B4. By 2011 the CABG market is 425,000 per year. The selling price per patient is $700. In 2010 market penetration is 15% and sales are 45 mil. In 2011 we are at 40% penetration and 120 mil revs. Revs peak in 2012 at 180 mil and 61%. After all why wouldn't a surgeon use it? Because the late stage pipeline is for variations and combinations of an approved drug we value shares it at 7 X current revenues or 1.260 bil market cap. The current market cap is 127 mil.
Voila. I've created a 10 bagger. That was easy.
Dave
The company stated on the last call that they think that enrollment will be completed in November 07. that means data will be available about april or may 08 not 09
All the doubters keep pointing to Alexion's failure as the reason this will fail. It is a different drug with a different MOA. It is a good thing they kept trying to produce cancer drugs. If they would have stopped because prior ones failed people would just give up and die
DrBio - I misread the 4 day data for the 30 day data - but note that both were prespecified endpoints. Also note that even the 30 day ITT has a p value the same as MCU's PR'd numbers (p=~0.03).
alxn in trial had a p value of .08. it was the subset that had a p-value of .03
PRIMO-CABG published: Pexelizumab fails to significantly reduce death/MI in surgery patients
http://www.theheart.org/article/137597.do
Tue, 18 May 2004 21:30:00 Michael O'Riordan
Seattle, WA -The results of the largest prospective clinical trial investigating the use of the terminal complement inhibitor pexelizumab in CABG patients are now published in the May 19, 2004 issue of the Journal of the American Medical Association.1 The trial, led by Dr Edward D Verrier (University of Washington, Seattle), showed that while the drug trended toward reducing the combined incidence of death or MI in patients randomized to treatment, the results failed to achieve significance.
Dr Edward D Verrier
The study, known as Pexelizumab for Reduction in Infarction and Mortality in Coronary Artery Bypass Graft Surgery (PRIMO-CABG), was first presented at the 2003 American Heart Association Scientific Sessions in Orlando, FL and previously reported by heartwire.
The randomized, double-blind, placebo-controlled trial included 3099 patients undergoing CABG surgerywith and without concomitant valve surgeryenrolled at 205 centers in North America and Europe. On entry, patients were randomized to receive placebo or pexelizumab in a 2.0-mg/kg bolus or pexelizumab in a 2.0-mg/kg bolus followed by a 24-hour infusion of pexelizumab at 0.05 mg/kg per hour.
The primary analysis was a composite of the incidence of all-cause mortality or MI at 30 days in the CABG-only population (n=2746). Secondary analysis included the composite end point of death/MI in the CABG-only patients at day 4, death/MI in the overall intent-to-treat population (CABG patients with and without valve surgery) at day 4 and day 30, and death at 90 days.
In the CABG-only population, treatment with pexelizumab resulted in an 18% relative reduction in risk of death/MI at 30 days compared with placebo. Although this primary end point failed to achieve significance, investigators report that when the overall results in the intent-to-treat population were analyzeda prespecified secondary analysis that includes CABG patients with and without concomitant valve surgerytreatment with pexelizumab did result in a statistically significant 18% relative risk reduction compared with patients receiving placebo.
Primary end point of death/MI at 30 days in the CABG-only populations
Primary end point
Placebo (n=1368)
Pexelizumab (n=1378)
Risk reduction
p
Death/MI at 30 days (%)
11.8
9.8
18
0.07
Secondary end point of death/MI at 4 days in CABG-only population
Secondary end point
Placebo (n=1368)
Pexelizumab (n=1378)
Risk reduction
p
Death/MI at 4 days (%)
10.0
7.4
26
0.01
Treatment effect in the overall intent-to-treat population (CABG patients with and without concomitant valve surgery)
Secondary end points
Placebo (n=1546)
Pexelizumab (n=1553)
Risk reduction
p
Death/MI day 4 (%)
11.9
9.1
24
0.008
Death/MI day 30 (%)
14.0
11.5
18
0.03
MI day 4 (%)
11.1
8.4
24
0.01
MI day 30 (%)
12.0
9.8
18
0.042
Death at 90 days (%)
4.8
3.6
25
0.096
To download tables as slides, click on slide logo below
"Compared with placebo, pexelizumab was not associated with a significant reduction in the risk of the composite end point of death or MI in 2746 patients who had undergone CABG surgery only but was associated with a statistically significant risk reduction at 30 days after the procedure among all 3099 patients undergoing CABG with and without valve surgery," conclude Verrier and colleagues.
The investigators suggest the study was underpowered to detect the observed drug effect in the CABG-only subpopulation. The PRIMO-CABG trial prespecified that 353 patients who underwent valve surgery be excluded from the primary analysis because pexelizumab was not believed to have a treatment effect in these patients.
In a post hoc analysis, event-free survival remained significantly improved through day 180, suggesting a reduction in early perioperative MI with pexelizumab results in a sustained reduction in clinical morbidity and mortality, they report.
In a previous interview with heartwire, Verrier noted that 67% of patients enrolled in the study had more than one risk factor. In these patients, pexelizumab significantly reduced the combined incidence of death or MI by 28%. He said that these results are particularly impressive considering that high-risk patients are more representative of the type of patients surgeons are seeing on the operating table.
primo cabg data
http://www.medscape.com/viewarticle/464397
I will take Medicure's data anyday
Return to Medscape coverage of: American Heart Association Scientific Sessions 2003
PRIMO-CABG: Pexelizumab for the Reduction of Infarction and Mortality in Coronary Artery Bypass Graft Surgery
Disclosures
Luis Gruberg, MD, FACC
Presenter: Edward Verrier, University of Washington (Seattle)
Since 1981, complement activation has been known to occur in patients who undergo coronary artery bypass graft (CABG) surgery. We also know that inflammation is a critical component of experimental ischemia, reperfusion injury, and clinical myocardial infarction (MI), and that it has been strongly implicated in the pathogenesis of atherosclerotic cardiovascular disease. Complement activation occurs in 2 phases in patients undergoing CABG surgery. Ischemia and biocompatibility of the bypass circuits activate C3 (which protects from bacterial infections by opsonization) and induce cleavage of C5 into C5a and C5b-9, which directly contribute to inflammation, vasoconstriction, vascular leakage, and leukocyte activation, with consequent cardiac damage and apoptosis.
Pexelizumab is a high-affinity, humanized anti-C-5 antibody fragment that blocks C-5 cleavage, thereby preventing inflammation.
Hypotheses
The phase 3, randomized, double-blind, placebo-controlled Pexelizumab for the Reduction of Infarction and Mortality in Coronary Artery Bypass Graft Surgery (PRIMO-CABG) study was undertaken to test 3 hypotheses:
Perioperative MI is highly predictive of long-term mortality.
Pexelizumab reduces perioperative MI.
The reduction in perioperative MI with pexelizumab results in a reduction in morbidity and mortality in patients undergoing CABG.
Endpoints
The primary endpoint of the study was the composite of all-cause mortality and MI at 30 days in patients undergoing CABG with cardiopulmonary bypass, with or without valve surgery.
Secondary endpoints included:
Composite of death and MI by intention-to-treat analysis at 4 and 30 days
Composite of death and MI in CABG-only patients at 4 days
Death at 180 days.
Study Design
The study enrolled a total of 3099 patients at 205 centers in Europe and North America. Patients undergoing CABG only (n = 2746) or CABG with valve surgery (n = 353) who had > 1 preoperative risk factor (ie, diabetes mellitus, prior CABG, prior MI) were randomized in a double-blind fashion to either pexelizumab (bolus + infusion) (n = 1378) or placebo (bolus + infusion) (n = 1368).
Results
Baseline clinical characteristics and risk factors were similar for both the pexelizumab and the placebo arms. Pexelizumab administration was associated with rapid and complete inhibition of serum complement activity for 24 hours, which normalized at 72 hours. The results from this study showed that perioperative myocardial damage clearly predicts mortality, as patients with a peak CK-MB > 100 ng/mL had a 15.9% mortality rate at 180 days compared with only 2.3% in patients with a peak CK-MB of < 20 ng/mL. Furthermore, MI (defined as a CK-MB > 100 ng/mL) at day 4 predicted mortality in these patients, irrespective of the type of surgery performed.
According to the results from this study, patients treated with pexelizumab had significantly lower rates of peak CK-MB, and thus, there was a significant reduction in the combined endpoint of death or MI in pexelizumab-treated patients who underwent CABG only (Figure 1) and in all pexelizumab-treated patients at 4-day follow-up (Figure 2).
Figure 1. PRIMO-CABG: death, MI, and death/MI in CABG-only patients at day 4.
Figure 2. PRIMO-CABG: death, MI, and death/MI in all patients at day 4.
At 30-day follow-up, there was a strong trend toward a reduction in the combined endpoint of death/MI in CABG-only treated patients (primary endpoint) (Figure 3). However, when evaluating the overall population, there was a significant 18% reduction in the primary endpoint (Figure 4). In addition, at 90 days, there was a trend toward a reduction in death in all pexelizumab-treated patients compared with the placebo group (3.6% vs 4.8%, respectively; P = .096). There was also no reported difference between the 2 groups with respect to the incidence of side effects or complications, including the rate of infections.
Figure 3. PRIMO-CABG: death, MI, and death/MI in CABG-only patients at 30 days.
Figure 4. PRIMO-CABG: death, MI, and death/MI in all patients at 30 days.
Conclusions
Investigators drew the following conclusions from their reported results:
Pexelizumab appears to be safe and well tolerated in patients undergoing CABG.
Perioperative MI predicts long-term morbidity and mortality.
Pexelizumab significantly reduces perioperative MI at day 4 and day 30.
Pexelizumab reduces death or MI in CABG-only patients at day 30 (primary endpoint).
Pexelizumab significantly reduces death or MI in CABG-only patients at day 4 and in the overall population at day 4 and day 30 (secondary endpoint).
Mortality benefit is sustained at 6-month follow-up.
Pexelizumab may have an even greater benefit in high-risk patients.
Discussant: Robert C. Robbins, Stanford University School of Medicine (Stanford, California)
More than 20 million patients have benefitted from cardiopulmonary bypass, which was first performed about 50 years ago. However, it has been well documented that there is a systemic inflammatory response from the contact of the heparinized blood with the foreign surfaces of the cardiopulmonary machine. The activation of the complement is one of the most important factors in this process.
Although the results from this study are positive, they also show us that there is a redundancy of the complement activation with probable activation of the system via complement C-3. Further trials are currently under way to determine whether systemic inhibition of both systems will have a more profound effect in patients undergoing heart surgery with cardiopulmonary bypass.
Copyright © 2003 Medscape.
In the primary pre-pivotal trial in CABG (PRIMO-CABG):
a) It was about a 24% reduction in MI/Death
b) The 30 day p value was 0.01
send the link
Why did it happened? These were large double blind trials with low p values. Why is that (and that is not only Alexion) that you frequently have great double blind phase II and phase II results followed by a bomb in the pivotal trial?
Anybody has any good explanation?
Everyone says how wonderful alexion trial was. They had an 18 percent reduction of events with a p value of .08 in a 3 or 4 thousand patient trial
mcu had a 37 percent reduction with a p value of .028 in a 300 patient arm
is everyone nutz
Bill Radvak is a nice guy. I spoke with him and he actually approached to board that the time is right to get an operations guy
His thoughts are between the 3m infectious disease and upcoming cardio ramp they will need more of an operations guy.
Is your interpretation that these must have been sicker or elderly patients, given that they got a less-intense transplant regimen ?
you hit the nail on the head, historically they have worse outcomes from the transplant surgery
does orbec work for this
If the cancer was found early and enteritis symptoms are happening during radiation therapy, it may be possible to stop or reduce the dosage of radiation for a short period of time. It is important for you to report all symptoms to your doctor so adjustments can be made as soon as possible to prevent permanent damage.
Unfortunately, there often are no good treatments for chronic radiation enteritis. The best approach is to control the symptoms. This includes eating small frequent meals and taking anti-diarrheal or anti-spasmodic agents.
probably
fully believe it is a component of the MI portion of the endpoint. But MCU very carefully steers away from actually saying it is THE definition of MI. For an example, see the Alexion trials where they had an SPA (i.e. the FDA almost certainly put in the endpoint they wanted) and the definition of MI was not limited to CKMB>100.
Also note that Alexion had results in CKMB that were just as encouraging as MCUs and utterly bombed in the pivotal trials - my guess is that it is possible to change the way that the damage to the heart expresses itself without actually decreasing the damage. Hence the decoupling of CKMB from actual MIs.
Note again that the physician diagnosed MI rate in the last trial is the offsetting factor to this. But I'd want to see a published paper/poster expressing the fact that this was done blinded etc.
thank you for your thoughtful response
fid mcu
short it and f-off
Phase III Trial of Progesterone for the Prevention of Preterm Birth in Women with a Previous Preterm Birth Earlier than 35 Weeks Does Not Meet Endpoints
Sunday February 4, 5:00 pm ET
Management to Hold Investor Conference Call at 8:30 am ET Monday
LIVINGSTON, N.J.--(BUSINESS WIRE)--Columbia Laboratories, Inc. (NASDAQ: CBRX - News) today announced its Phase III clinical trial of progesterone for the prevention of preterm birth in women with a previous preterm birth earlier than 35 weeks gestation did not achieve any reduction in the incidence of preterm birth at week 32, the primary endpoint, or at weeks 28, 35 and 37, secondary endpoints of the study.
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Of the 611 evaluable patients in this randomized, placebo-controlled, double blind clinical trial, 302 received placebo and 309 received PROCHIEVE® 8% (progesterone gel). The mean gestational age at delivery was approximately 37 weeks in both the active and placebo groups following treatment, an improvement from a mean of 30 weeks in the previous preterm birth for both groups. Over 60 percent of evaluable patients had a previous preterm birth at or below 32 weeks gestation; prior studies of progestins to prevent preterm birth were comprised mainly of patients with prior preterm births at 34 weeks or greater.
The incidence and profile of adverse events in patients receiving PROCHIEVE 8% was similar to placebo, which was as expected given the product's documented safety history.
The Company is conducting detailed analyses of the study data, and intends to report the results of this trial in more detail at appropriate scientific venues.
"These study results are extremely disappointing. Despite solid evidence in this and other studies that PROCHIEVE 8% effectively delivers progesterone to the uterus, there was no difference in the reduction of preterm birth incidence in patients with a previous preterm birth earlier than 35 weeks and treated with progesterone versus placebo at any endpoint," said Robert S. Mills, president and chief executive officer of Columbia Laboratories.
"Although disappointed by these results, we have managed our resources carefully so that Columbia is in a strong position to build our existing infertility business. With our December 2006 acquisition of the U.S. marketing rights to CRINONE® progesterone gel, we are now able to address both of our key infertility audiences, the reproductive endocrinologists and the obstetricians and gynecologists, with the only progestin FDA-approved for use in infertility and for use during the first trimester of pregnancy. We also intend to continue to leverage our bioadhesive drug delivery system for proprietary and third-party opportunities, including our Phase II lidocaine candidate for the prevention and relief of dysmenorrhea," concluded Mills.
Conference Call
Management will host a conference call to discuss the study results on Monday, February 5, 2007 at 8:30 AM ET at (800) 565-5442 or (913) 312-1298 and online at www.cbrxir.com, under "Events."
The teleconference replay will be available two hours after completion of the call through Friday, February 9, 2007 at (888) 203-1112 or (719) 457-0820, passcode 8491341. The archived webcast will be available for one year on the Company's investor website, www.cbrxir.com, under "Events."
About PROCHIEVE 8%
PROCHIEVE® 8% (progesterone gel) is FDA-approved for progesterone supplementation or replacement as part of Assisted Reproductive Technology (ART) treatment for infertile women with progesterone deficiency and for the treatment of secondary amenorrhea. Several trials showing these benefits have been published. PROCHIEVE 8% is safe for use during pregnancy, and has been safely used by tens of thousands of women globally to help sustain pregnancy at the early stages for almost ten years.
The most common side effects of PROCHIEVE 8% include breast enlargement, constipation, somnolence, nausea, headache, and perineal pain. PROCHIEVE 8% is contraindicated in patients with active thrombophlebitis or thromboembolic disorders, or a history of hormone-associated thrombophlebitis or thromboembolic disorders, missed abortion, undiagnosed vaginal bleeding, liver dysfunction or disease, and known or suspected malignancy of the breast or genital organs.
For more information, please visit www.prochieve8.com.
About Columbia Laboratories
Columbia Laboratories, Inc. is a U.S.-based international pharmaceutical company dedicated to the development and commercialization of reproductive healthcare and endocrinology products that use its novel bioadhesive drug delivery technology. Columbia markets CRINONE® 8% (progesterone gel) and PROCHIEVE® 8% (progesterone gel) in the United States for progesterone supplementation as part of Assisted Reproductive Technology treatment for infertile women with progesterone deficiency, and PROCHIEVE 4% (progesterone gel) for the treatment of secondary amenorrhea. The Company also markets STRIANT® (testosterone buccal system) for the treatment of hypogonadism in men. For more information, please visit www.columbialabs.com.
Safe Harbor Statement Under the Private Securities Litigation Reform Act of 1995: This press release contains forward-looking statements about Columbia Laboratories, Inc.'s expectations regarding the Company's strategic direction, prospects and future results, which statements are indicated by the words "will," "plan," "expect" and similar expressions. Such forward-looking statements are subject to certain risks and uncertainties; actual results may differ materially from those projected in the forward-looking statements. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date on which they are made. Factors that might cause future results to differ include, but are not limited to, the following: the successful marketing of CRINONE® 8% (progesterone gel), PROCHIEVE® 8%(progesterone gel), PROCHIEVE 4% (progesterone gel), and STRIANT® (testosterone buccal tablet) in the U.S.; the timely and successful development of new products; the timely and successful completion of clinical studies; the impact of competitive products and pricing; competitive economic and regulatory factors in the pharmaceutical and healthcare industry; general economic conditions; and other risks and uncertainties that may be detailed, from time-to-time, in Columbia's reports filed with the Securities and Exchange Commission. Columbia Laboratories undertakes no obligation to publicly update any forward-looking statements.
CRINONE®, PROCHIEVE® and STRIANT® are registered trademarks of Columbia Laboratories, Inc.
Contact:
Columbia Laboratories, Inc.
James A. Meer, 973-486-8860
Senior Vice President, CFO & Treasurer
or
Investor and Media:
Rx Communications, LLC
Melody A. Carey, 917-322-2571
Co-President
--------------------------------------------------------------------------------
Source: Columbia Laboratories, Inc.
check out ACCP. market cap of only $14 million. huge article coming out in business week soon. just got fda approval for their product. they have another product in phase 2 that may be a blockbuster. most bio-tech/pharma companies without an fda approved drug have market caps over $500 million. this one has a market cap of $14 million, a potential blockbuster in phase 2 and a drug already approved for the market?????
I don't know where the fellow in business week came out with the 14 million market cap but a financing in early 2006 was done for 5 million dollars at 22 cents that is about 25 million shares. there was also 75 percent warrant coverage at 26 cents, so that is about another 18 million shares. That financing alone was about 43 million shares so it responsible after the 1 for 5 reverse split of over 8 million shares.
the price was about 3 when the article hit so just the shares in the financing are worth over 24 million. He should take up math before he pumps stocks. SCO has done great with this stock
First we should call the company and try to verify exactly how MI will be measured and how that corresponds to the data from P2. Trying to raise 20 mil for the P3 trial they actually raised 25 mil. Some institutions believe.
Call the company and validate the ck-mb measurement. It is what you think. You have some people on the board that are making you doubt yourself so you should validate it and become more comfortable. The paragraph below is from the press release about recieving the spa. Why would they release peak CK-MB greater than or equal to 100ng/mlif it wasn't the endpoint in the trial. When they say the entry criteria closely follow the phase 2 it is mainly because the trial will only have the 250ml dose, the trial will be larger and stroke will be treated as an adverse event but not part of the primary endpoint. All these changes increase the chance of reaching statistical significance in the phase 3.
The study protocol and entry criteria for MEND-CABG II closely follow that of the Phase II MEND-CABG study. MEND-CABG was a Phase II study involving 901 patients that evaluated MC-1 versus placebo in patients undergoing CABG surgery. The 250 mg dose of MC-1 had a 37.2% reduction in the composite of cardiovascular death, non-fatal myocardial infarction (peak CK-MB greater than or equal to 100ng/ml), and non-fatal stroke versus placebo (p equals 0.028). The reduction in the composite endpoint was driven by a significant 46.9% decrease in the incidence of non-fatal myocardial infarction (peak CK-MB greater than or equal to 100ng/ml) with the 250 mg dose of MC-1 versus placebo (p equals 0.008).
enough said
rfj---mcu
I will argue the point with you because you are open minded. There is someone else on the board that answers questions with questions and doesn't respond to evidence properly.
Sell. The evidence for MC-1 efficacy isn't remotely strong enough to warrant anything more than a trivial investment.
can you specifically say why you believe the data wasn't remotely strong enough. In the 250ml trial they had a 37 percent reduction of non fatal mi death and stroke. In the 750ml dose they had a 31 percent reduction in non fatal mi, death, and stroke. There is someone on the board that keeps on switching the endpoint asking people to explain why there were more strokes if you combine the two active arms than in the placebo. That is playing with numbers. There were twice as many people in the two active arms. Aside from that there were 37 and 31 percent reductions in events when you include stroke. Lets say you have 2 more strokes but you prevent 7 heart attacks that is a risk benefit to make. Lucentis has a higher stroke rate on people taking the drug for AMD. A risk benefit assesment is made to determine if the small risk in getting a stroke is worth the fact that you will maintain your vision and not go blind. There is nothing in the MOA of MC-1 that should increase the chances of getting a stroke. In fact the only reason it was included in the endpoint was because the the method of action would probably reduce the severity of any stroke that occurred but that doesn't mean it would prevent stroke so they were naive in this respect. Since there is no reason to think the drug will prevent stroke it helps the chances of achieving statistical significance by taking it out of the numerator and denominator. Death by itself is not something that is expected to be prevented in this 30 day trial. The regulators know that if you reduce additional heart attacks and the strain and damage on the heart that they cause you will be reducing death over the long term. The drug doesn't have to reduce death in 30 days to have a meaningful benefit. Reducing non fatal mi is all it needs to do. As long as it doesn't increase death, which it shouldn't.
Plus MCU is headed for a disaster trying to sell tirofiban; getting uptake for this agent will require real expertise and substantial marketing spend. And as far as I can tell MCU has neither the expertise nor enough cash to do the job properly.
The company paid 17 million for a drug that was getting no promotion and doing 10 million in sales. The people they are selling aggrastat to are the same docs falling over themselves to be in the mc-1 trials. If MC-1 gets approved they will be selling both drugs to the same docs. This was a great deal if they increase sales a little. They don't have to triple or quadruple sales for the deal to make sense.
In short, let other investors suffer through this. If MC-1 is effective, there will be plenty of time to buy.
if what you say here made sense than no stocks would go up until the data is released. I am betting that a good partnership gets done fairly soon which will include a copromotion piece which will validate the aggrastat deal. I also believe publication of the phase 2 trial will validate MC-1. These items should substantially change the stock price for the better before the phase 3 trial is finished
Anyone want to argue specifics, go ahead.
unfortunately the 2 questions some of us had regarding the data were not asked:
it is amazing that only 2 questions weren't asked
1. survival benefit was limited to mismatched patients (likely because these patients overall do worse and have a higher mortality rate)..but what about other endpoints? (i.e. would be nice to know that perfectly matched patients also saw a benefit of therapy)
the survival benefit was better on the mismatched but it would take a larger trial to prove that to statistical significance which is why it was a surprise that they had this tremendous benefit in such a small trial and why it wasn't the primary endpoint. It is also amazing not only that they had the suvival benefit but even the 50 day trend and 80 day statistical significance when you look at the fact that the sicker patients [non-myeloablative] and higher risk of relapse patients were in the orBec arm. As you know drugs have a tough time getting approved if you use subset analysis. I think if the company tries to go in and figure out if the patients who were not mismatched did as well in the other endpoints they would actually be ruining the fact that they made statistical significance in the secondary endpoints in the trial as a whole. The important endpoints were positive in the trial as a whole. Why try to disprove it using subsets?
2. is there a possibility of a negative interaction between prednisone and orbec when coadministered given the higher failure rate during the initial treatment phase? (this was tangentially mentioned as a "fluke" towards the end of the Q&A - i think the data as a whole, including the lack of interaction in phase 2 (actually there was a benefit to the prednisone-orbec arm during coadministration in the phase 2), greatly mitigate this concern but I still would have liked to hear the argument DOR would give regulators if this was brought up)
I believe the best answer is the fact that there was no interaction problem in the phase 2[orbec worked better in the first 10 days] and the fact that 3 people in the orbec arm actually were too sick and shouldn't have been admitted into the trial, are the best answers and especially the panel will realize this.
I have my own reasons to think neither of these issues will impede full approval, but this was now the second missed opportunity to try and get clarification on these points from 2 separate investigators in the trial..bit of a shame
The company announced their intention in mid-2006 to sign a partner by 4Q06. No partner has been signed. These are the logical possibilities as I see them:
1) No one is interested in the company.
2) Interested parties know the company is running low on cash and are stalling in order to steal talabostat.
3) Management knows something good is going to happen in Q107 or Q207 and the $4+ million is a stopgap measure.
It seems to me there is additional stock price weakness ahead. Your thoughts would be appreciated.
Everything you said is true. The didn't do placebo controlled trials in phase 2 and didn't have the cash to finish the phase 3, so my take is that if you work in business development in Pfizer do you want to spearhead a deal that could fail in a year and you get fired or do want to buy a company that will have data in 5 years. By then you will be at another company.
I knew there was financing risk in this investment but I didn't think it would be this bad. That being said I think the drug works and won't sell the stock I have, I would buy more if they could get the money to finish the trial
Management screwed this up big time. I don't know what this 4 million did for them
Oral beclomethasone dipropionate (orBec®) for Transplant-related
GI GVHD: A Clinical Update
Webcast is still availeble on replay
A Live Presentation with Lead Investigator on New Data Published in Blood: The Journal of the American Society of Hematology
An “invitation-only” webinar will review highlights of late-stage clinical data demonstrating a long-term survival benefit with oral beclomethasone dipropionate (orBec®) in the treatment of gastrointestinal Graft-versus-Host disease resulting from allogeneic stem cell or bone marrow transplants, as published in the January 23 online edition of Blood.
A Question and Answer period will follow with the lead investigator and a representative from DOR BioPharma.
When: 1:00 p.m. ET (10:00 a.m. PT)
Tuesday, January 30, 2007
Where: Webinar address: http://www.videonewswire.com/event.asp?id=37602
Password: DOR (all caps)
(Please visit the above web address prior to day of event to register.)
Telephone dial-in: (800) 896-8445
Passcode: DOR
Overview: The webinar will feature leading gastroenterologist Dr. David M. Hockenbery, Professor of Medicine at the University of Washington School of Medicine and member of the Clinical Research and Human Biology Divisions at the Fred Hutchinson Cancer Research Center in Seattle, Washington. Dr. Hockenbery is also the lead investigator for the oral beclomethasone dipropionate clinical trials.
During the webinar, Dr. Hockenbery will discuss:
§ Clinical data published in Blood including long term survival data
§ Role of orBec® as potential prednisone-sparing therapy for GI GVHD
RSVP: Please RSVP to Heather Ioset:
hioset@bmccommunications.com
(212) 477-9007 x20
Please feel free to forward this information to your colleagues.
Webinar regarding orBec moderated by lead investigator
The webcast is still availeble on replay
Oral beclomethasone dipropionate (orBec®) for Transplant-related
GI GVHD: A Clinical Update
A Live Presentation with Lead Investigator on New Data Published in Blood: The Journal of the American Society of Hematology
An “invitation-only” webinar will review highlights of late-stage clinical data demonstrating a long-term survival benefit with oral beclomethasone dipropionate (orBec®) in the treatment of gastrointestinal Graft-versus-Host disease resulting from allogeneic stem cell or bone marrow transplants, as published in the January 23 online edition of Blood.
A Question and Answer period will follow with the lead investigator and a representative from DOR BioPharma.
When: 1:00 p.m. ET (10:00 a.m. PT)
Tuesday, January 30, 2007
Where: Webinar address: http://www.videonewswire.com/event.asp?id=37602
Password: DOR (all caps)
(Please visit the above web address prior to day of event to register.)
Telephone dial-in: (800) 896-8445
Passcode: DOR
Overview: The webinar will feature leading gastroenterologist Dr. David M. Hockenbery, Professor of Medicine at the University of Washington School of Medicine and member of the Clinical Research and Human Biology Divisions at the Fred Hutchinson Cancer Research Center in Seattle, Washington. Dr. Hockenbery is also the lead investigator for the oral beclomethasone dipropionate clinical trials.
During the webinar, Dr. Hockenbery will discuss:
§ Clinical data published in Blood including long term survival data
§ Role of orBec® as potential prednisone-sparing therapy for GI GVHD
RSVP: Please RSVP to Heather Ioset:
hioset@bmccommunications.com
(212) 477-9007 x20
Please feel free to forward this information to your colleagues.
mc-1 stroke
reduction of stroke has never been part of the endpoints in these kinds of trials. Medicure asked it to be part of the endpoint in the phase 2 because the moa of the drug would lead you to believe that it may reduce the symptoms of a stroke. Reducing symptoms of a stroke is a lot different than preventing one from happening. They were naive to have it included as an endpoint.
stroke will be followed as an adverse event where it belongs
in the 250 ml dose the reduction of mi, death and stroke of 37 percent with a p value of .028 would have been closer to 45 percent reduction with a p value less than .01 just by taking stroke out of the numerator. They will have that advantage in the phase 3.
Since it can't prevent a stroke but you track it as an endpoint you are paying a penalty to have it in both the numerator and denominator in your p value calculation.
One man and his deer.
When a deer hunting man in Tallahasse took one of his wins to a check station, he had a rather shocking surprise - it transpires the deer had both male and female sex organs. "I've been doing this for 27 years, and I've only come across three hermaphrodite deer" (hmm, more than most). Hermaphrodite deer's are apparently very rare, however the condition can also occur in humans - on extremely rare occasions a hermaphrodite may even impregnate itself. As one can imagine, this would lead to rather serious complications.
FDA Advisory Committee to Review DOR BioPharma's orBec(R) for the Treatment of GI GVHD
Wednesday January 31, 8:09 am ET
MIAMI, FL--(MARKET WIRE)--Jan 31, 2007 -- DOR BioPharma, Inc. (OTC BB:DORB.OB - News) ("DOR" or "the Company") announced that it has received notification from the U.S. Food and Drug Administration ("FDA") that the Oncology Drug Advisory Committee ("ODAC") will review the New Drug Application (NDA) for orBec® (oral beclomethasone dipropionate) for the treatment of gastrointestinal Graft-versus-Host disease ("GI GVHD") on May 9, 2007. The FDA has previously said it will respond to DOR's NDA by July 21, 2007 in accordance with the Prescription Drug User Fee Act (PDUFA).
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"The setting of an advisory committee meeting date marks an important next step in the orBec® NDA review process," stated Christopher J. Schaber, Ph.D., President and Chief Executive Officer of DOR BioPharma. "We are very pleased to have this opportunity to present the orBec® data in GI GVHD to the ODAC panel and we look forward to reviewing our application with the FDA advisors."
The data provided in the NDA submission demonstrate that orBec® may provide a higher rate of survival when compared with the current standard of care, and a lowered exposure to systemic corticosteroids following allogeneic transplantation. Currently there are no approved products to treat GI GVHD. Thus an approval of orBec® would represent the first directed therapy for GI GVHD.
The NDA filing is supported by data from two randomized, double-blinded, placebo-controlled clinical trials. The first trial was a 129-patient pivotal Phase 3 multi-center clinical trial of orBec® conducted at 16 leading bone marrow/stem cell transplant centers in the U.S. and France. The second trial was a 60-patient Phase 2 single-center clinical trial conducted at the Fred Hutchinson Cancer Institute. Although orBec® did not achieve statistical significance in the primary endpoint of its pivotal trial, namely time to treatment failure through Day 50 (p-value 0.1177), orBec® did achieve statistical significance in other key outcomes such as median time to treatment failure through Day 80 (p-value 0.0226) and, most importantly, demonstrated a statistically significant long-term survival advantage compared with placebo.
In the pivotal Phase 3 trial, analysis of patient survival at the pre-specified endpoint of 200 days post-transplant showed a clinically meaningful and statistically significant 66% reduction (p-value 0.0139) in mortality among patients randomized to orBec®. In the pivotal Phase 3 trial, a subgroup analysis also revealed that patients dosed with orBec® who had received stem cells from unrelated donors had a 94% reduction in the risk of mortality 200 days post-transplant.
orBec® further showed continued survival benefit when compared to placebo one year after randomization in the pivotal Phase 3 trial. Overall, 18 patients (29%) in the orBec® group and 28 patients (42%) in the placebo group died within one year of randomization (46% reduction in mortality, hazard ratio 0.54, 95% CI: 0.30, 0.99, p=0.04, stratified log-rank test). Results from the Phase 2 trial also demonstrated enhanced long-term survival benefit with orBec® versus placebo. In that study, at one year after randomization, 6 of 31 patients (19%) in the orBec® group while 9 of 29 patients (31%) in the placebo group had died (45% reduction in mortality, p=0.26). Pooling the survival data from both trials demonstrated that the survival benefit of orBec® treatment was sustained long after orBec® was discontinued and extended well beyond 3 years after the transplant. The risk of mortality was 37% lower for patients randomized to orBec® compared with placebo (hazard ratio 0.63, p=0.03, stratified log-rank test).
About FDA Advisory Committees
To keep up with the challenges that the FDA's full-time experts face when reviewing innovative and rapidly evolving technologies, the agency hires "special government employees" whose opinions complement its goals to provide safe and effective products.
These outside advisers make up the FDA's technical and scientific advisory committees. The primary role of an advisory committee is to provide independent advice that will contribute to the quality of the agency's regulatory decision-making and lend credibility to the product review process. In this way, the FDA can make sound decisions about new medical products and other public health issues. And although advisory committees have a prominent role in the product approval stage, they are sometimes included earlier in the product development cycle and are asked to consider issues relating to products already on the market.
Committees typically are asked to comment on whether adequate data supports approval, clearance, or licensing of a medical product for marketing. Advisory committees also may recommend that the FDA request additional studies or suggest changes to a product's labeling. Their recommendations are just that -- advice -- and do not bind the agency to any decision. While committee discussions and final votes are very important to the FDA, the final regulatory decision rests with the agency.
Membership in advisory committees must be "fairly balanced" -- that is, as open and inclusive as possible -- according to the law. Committee membership is expected to include ethnic, gender, and geographic diversity, as well as people with recognized expertise and judgment in a specific field, such as clinicians and researchers. Most members of the FDA's drug advisory committees, for example, are physician-scientists whose specialties or research involve the kinds of products being reviewed. Other members might include statisticians, epidemiologists, nutritionists, and toxicologists -- experts in preclinical (animal) studies. The FDA also insists on getting industry and public perspectives, and nearly all committees include industry and consumer representation.
About GI GVHD
GVHD is a debilitating and painful disease. It is a common disorder among immunocompromised cancer patients after receiving allogeneic stem cell or bone marrow transplants. Unlike organ transplants where the patient's body may reject the organ, in GVHD it is the donor cells that begin to attack the patient's body -- most frequently the gut, liver and skin. Patients with mild-to-moderate GI GVHD typically develop symptoms of anorexia, nausea, vomiting and diarrhea. If left untreated, GI GVHD can progress to ulcerations in the lining of the GI tract, and in its most severe form, can be fatal.
orBec® is a two-tablet system containing the highly potent, topically active corticosteroid beclomethasone dipropionate, and is designed to specifically target and treat upper and lower GI GVHD with reduced systemic immunosuppressive side effects. Systemic immunosuppressive agents such as prednisone, which are the current standard treatments for GI GVHD, are associated with high mortality rates due to infection and debility. Further, these drugs have not been approved for treating GI GVHD in the European Union or in the U.S., but rather are used off-label as investigational therapies for this indication.
About Allogeneic Bone Marrow/Stem Stem Cell Transplantation (HSCT)
Allogeneic hematopoietic stem cell transplantation ("HSCT") is considered a potentially curative option for many leukemias as well as other forms of blood cancer. In an allogeneic HSCT procedure, hematopoietic stem cells are harvested from a closely matched relative or unrelated person, and are transplanted into the patient following either high-dose chemotherapy or intense immunosuppressive conditioning therapy. The curative potential of allogeneic HSCT is now partly attributed to the so-called graft-versus-leukemia ("GVL") or graft-versus-tumor ("GVT") effects of the newly transplanted donor cells to recognize and destroy malignant cells in the recipient patient.
The use of allogeneic HSCT has grown substantially over the last decade due to advances in human immunogenetics, the establishment of unrelated donor programs, the use of cord blood as a source of hematopoietic stem cells and the advent of non-myeloablative conditioning regimens ("mini-transplants") that avoid the side effects of high-dose chemotherapy. Based on the latest statistics available, it is estimated that there are more than 10,000 HSCT procedures annually in the U.S. and a comparable number in Europe. Estimates as to the current annual rate of increase in these procedures are as high as 20%. High rates of morbidity and mortality occur in this patient population. Clinical trials are also underway testing allogeneic HSCT for treatment of some metastatic solid tumors such as breast cancer, renal cell carcinoma, melanoma and ovarian cancer. Allogeneic transplants have also been used as curative therapy for several genetic disorders, including immunodeficiency syndromes, inborn errors of metabolism, thalassemia and sickle cell disease. The primary toxicity of allogeneic HSCT, however, is GVHD in which the newly transplanted donor cells damage cells in the recipient's gastrointestinal tract, liver and skin.
About orBec®
orBec® represents a first-of-its-kind oral, locally acting therapy tailored to treat the gastrointestinal manifestation of GVHD, the organ system where GVHD is most frequently encountered and highly problematic. orBec®, if approved by the EMEA and the FDA, would be the first oral formulation of beclomethasone dipropionate ("BDP") available in the European Union and the United States, respectively. orBec® is intended to reduce the need for systemic immunosuppressive drugs to treat GI GVHD. BDP is a highly potent, topically active corticosteroid that has a local effect on inflamed tissue. BDP has been marketed in the U.S. and worldwide since the early 1970s as the active pharmaceutical ingredient in a nasal spray and in a metered dose inhaler for the treatment of patients with allergic rhinitis and asthma. orBec® is formulated for oral administration as a single product consisting of two tablets; one tablet is intended to release BDP in the proximal portions of the GI tract and the other tablet is intended to release BDP in the more distal portions of the GI tract.
In addition to issued patents and pending worldwide patent applications held by or exclusively licensed to DOR, orBec® also benefits from orphan drug designations in the U.S. and in Europe for the treatment of GI GVHD, which provide for 7 and 10 years of post-approval market exclusivity, respectively.
About DOR BioPharma, Inc.
DOR BioPharma, Inc. is a biopharmaceutical company developing products to treat life-threatening side effects of cancer treatments and serious gastrointestinal diseases, and vaccines for certain bioterrorism agents. DOR's lead product, orBec® (oral beclomethasone dipropionate), is a potent, locally acting corticosteroid being developed for the treatment of GI GVHD, a common and potentially life-threatening complication of bone marrow transplantation. DOR has filed an NDA with the FDA for the treatment of GI GVHD, and has received an FDA PDUFA date of July 21, 2007. An MAA with the EMEA for orBec® has also been filed and validated. orBec® may also have application in treating other gastrointestinal disorders characterized by severe inflammation.
Through its Biodefense Division, DOR is developing biomedical countermeasures pursuant to the recently enacted Project BioShield Act of 2004. DOR's biodefense products in development are recombinant subunit vaccines designed to protect against the lethal effects of exposure to ricin toxin and botulinum toxin. The ricin toxin vaccine, RiVax™, has been evaluated successfully in a Phase 1 clinical trial in normal volunteers.
For further information regarding DOR BioPharma, please visit the Company's website located at www.dorbiopharma.com.
This press release contains forward-looking statements, within the meaning of Section 21E of the Securities Exchange Act of 1934, that reflect DOR BioPharma, Inc.'s current expectations about its future results, performance, prospects and opportunities, including statements regarding the potential use of orBec® for the treatment of gastrointestinal GVHD and the prospects for regulatory filings for orBec®. Where possible, DOR has tried to identify these forward-looking statements by using words such as "anticipates," "believes," "intends," or similar expressions. These statements are subject to a number of risks, uncertainties and other factors that could cause actual events or results in future periods to differ materially from what is expressed in, or implied by, these statements. DOR cannot assure you that it will be able to successfully develop or commercialize products based on its technology, including orBec®, particularly in light of the significant uncertainty inherent in developing vaccines against bioterror threats, manufacturing and conducting preclinical and clinical trials of vaccines, and obtaining regulatory approvals, that its technologies will prove to be safe and effective, that its cash expenditures will not exceed projected levels, that it will be able to obtain future financing or funds when needed, that product development and commercialization efforts will not be reduced or discontinued due to difficulties or delays in clinical trials or due to lack of progress or positive results from research and development efforts, that it will be able to successfully obtain any further grants and awards, maintain its existing grants which are subject to performance, enter into any biodefense procurement contracts with the U.S. Government or other countries, that the U.S. Congress may not pass any legislation that would provide additional funding for the Project BioShield program, that it will be able to patent, register or protect its technology from challenge and products from competition or maintain or expand its license agreements with its current licensors, or that its business strategy will be successful. Important factors which may affect the future use of orBec® for gastrointestinal GVHD include the risks that: because orBec® did not achieve statistical significance in its primary endpoint in the pivotal Phase III clinical study (i.e. a p-value of less than or equal to 0.05), the FDA may not consider orBec® approvable based upon existing studies, orBec® may not show therapeutic effect or an acceptable safety profile in future clinical trials, if required, or could take a significantly longer time to gain regulatory approval than DOR expects or may never gain approval; DOR is dependent on the expertise, effort, priorities and contractual obligations of third parties in the clinical trials, manufacturing, marketing, sales and distribution of its products; or orBec® may not gain market acceptance; and others may develop technologies or products superior to orBec®. These and other factors are described from time to time in filings with the Securities and Exchange Commission, including, but not limited to, DOR's most recent reports on Form 10-QSB and Form 10-KSB. DOR assumes no obligation to update or revise any forward-looking statements as a result of new information, future events, and changes in circumstances or for any other reason.
Contact:
Company Contact:
Evan Myrianthopoulos
Chief Financial Officer
(786) 425-3848
http://www.dorbiopharma.com
Investor Contacts:
Lippert/Heilshorn & Associates
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Email Contact
(212) 838-3777
Bruce Voss
Email Contact
(310) 691-7100
medicure mc-1
If this phase III succeeds (which i doubt it), I'll make a $5 wager with you that approved MC-1 goes the way of BiDil.
In the meantime, I'll keep quiet on this topic.
The above comment you made shows the bias you have in this instance. You can doubt the the trial succeeds although the data from the prior trial seems to make chances of success better than in most cases. In fact the fda even thinks so because they allowed the data from the phase 2 trial to be used as a pivotal trial. They don't usually do that.
To say that the drug would go the way of bidil is a misconception on your part. The failure of Bidil was more a function of the drug being targeted to African Americans than the problem it had with generic alternatives which can be shown by looking at the fact that even people with medicaid. They aren't getting Bidil prescriptions filled even though they pay nothing for them. They would not care about generic alternatives.
As I believe Daved previously posted, a hospital that prescribes generic P5P or vitamin b-6 to the first person that dies after the surgery would be sued for not prescribing the FDA approved drug from its hospital formulary.
by the way there are articles that have been posted In the New England Journal of Medicine which makes it clear that B-6 does not work in the indication.
You can continue to be biased if you like. The stock will either sit here or go up without your ownership
Most companies do go down about 70 percent if they fail phase 3 but in the case of ymi it is a surprise becsause the stock was fairly cheap to begin with and I think most people are in it for nimo.
ymi getting killed in US and I beleive halted in Canada
inside joke between me an ioio
this is turning into a decent board.
I hope we won't have to ban you. Hopefully there aren't any moderators here that will turn it into a full time job
Most of the survival benefit came from the mismatched donors, true. But there was a tremendously reduced difference in treatment failures in favor orbec at day 50 and day 80.
It was only treatment thru day 50 that showed a trend and not statistical significance. As far as the reason that more patients failed on orBec in the first 10 days, the patients were sicker in the orBec arm and the drug may not have had enough time to work.
I believe they can get passed this because in the phase 2 trial there was a clear benefit to orBec in the first 10 days. They should have included that in the article, but the FDA has that info.
Topical Steroid, Now a Pill, Lowers Risk of GvHD
it appears the study will be part of cme classes for doctors so they are aware of it. Article was reviewed by major professor at University of Pennsylvania. That is how to sell a drug, get the data to the thought leaders.
By Michael Smith, Senior Staff Writer, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
January 24, 2007
Additional Leukemia & Lymphoma Coverage
http://www.medpagetoday.com/HematologyOncology/LeukemiaLymphoma/tb/4919
SEATTLE, Jan. 24 -- Gastrointestinal graft-versus-host disease has been significantly reduced following allogeneic stem-cell transplants by the use of a common topical corticosteroid that was reformulated into pill form, according to researchers here. Action Points
Explain to interested patients that an allogeneic hematopoietic stem-cell transplant can be a life-saving intervention for patients with a range of blood cancers, but that the transplant carries the risk of graft-versus-host disease.
Note that this study suggests that a widely used corticosteroid, reformulated into pill form, may reduce gastrointestinal graft-versus-host disease and overall mortality in such transplants.
The drug -- orBec (beclomethasone dipropionate, or BDP) -- reduced overall mortality as well in a multicenter phase III randomized, placebo-controlled trial of 129 patients, David Hockenbery, M.D., of the Fred Hutchinson Cancer Research Center here, and colleagues, reported online in Blood.
They also reported data from an earlier phase II randomized controlled trial of 60 patients conducted at the Hutchinson center.
The standard treatment for gastrointestinal graft-versus-host disease GvHD, which affects up to 60% of patients getting an allogeneic stem-cell transplant, is immune suppression with prednisone at between 1 mg/kg and 2 mg/kg, Dr. Hockenbery and colleagues noted.
The prednisone is tapered off to avoid its side effects, but the GVHD often recurs, they said.
BDP is usually formulated either as a topical medication for skin conditions or as a nasal spray for allergies. In orBec, the medication is in two 1 mg pills, one in an immediate-release formulation and one enteric-coated for a delayed release. The medication is taken four times daily for a total dose of eight mg.
The idea is that the drug will target the stomach and mid-small intestine, Dr. Hockenbery said, and allow the prednisone to be tapered off more rapidly. "Oral BDP provides much more tailored and targeted control of gastrointestinal GvHD and it allows patients to move away from the side effects of standard prednisone therapy," he said.
In the phase III study, patients were given 10 days of prednisone treatment and randomized to either orBec or placebo. If symptoms resolved by day 10, the prednisone was tapered off. On an intent-to-treat basis, the risk of GvHD-treatment failure was reduced, but not significantly for the BDP group at day 50 (hazard ratio 0.63, 95% CI 0.35-1.13).
However, the outcome of all clinically important secondary endpoints, including were statistically significantly better in the BDP group.
Among the 117 patients who were eligible for prednisone tapering, the risk of GvHD recurrence was significantly reduced by day 50, compared with the placebo group. The hazard ratio (HR) was 0.39 with a 95% confidence interval from 0.19 to 0.81, which was significant at P=0.009.
By day 200 post-transplant, five orBec patients had died, compared with 16 on placebo, a 67% reduction in the hazard of mortality, which was statistically significant at P=0.03.
At one year after randomization, the mortality benefit was still apparent -- 28 patients (42%) in the placebo group and 18 patients (29%) in the orBec group had died. The hazard ratio was 0.54 with a 95% confidence interval from 0.30 to 0.99, which was significant at P=0.04.
"I think this is a very convincing clinical trial because by targeting topical therapy to the areas most affected, we were able to keep symptoms at bay while minimizing systemic immune suppression," Dr. Hockenbery said.
The results confirm findings from the earlier study, Dr. Hockenbery said. That trial showed a 45% reduction in mortality a year after randomization, as well as a significant response at the end of the treatment phase.
The data were part of regulatory filings to the FDA and the European Medicines Evaluation Agency (EMEA) by DOR BioPharma, Inc., of Miami, which makes orBec.
The study was supported by a grant from the FDA and by Enteron Pharmaceuticals, Inc., a subsidiary of DOR BioPharma.
Three of the authors -- Scott Cruickshank, Ph.D. and Timothy Rodell, M.D., both of Enteron, and George McDonald, M.D., of the Hutchinson center -- reported financial links with the study sponsor. Each is a consultant to DOR BioPharma and Dr McDonald has an equity position in DOR BioPharma, Inc.
Additional Leukemia & Lymphoma Coverage
Earn CME/CE credit for reading the news.
Primary source: Blood
Source reference:
Hockenbery DM et al. "A randomized, placebo-controlled trial of oral beclomethasone dipropionate as a prednisone-sparing therapy for gastrointestinal graft-versus-host disease." Blood 2007;0: DOI 10.1182/blood-2006-05-021139.
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New Drug Therapy To Combat Graft-vs.-host Disease In Stem-cell Patients Shows Significant Reduction In Deaths
http://www.sciencedaily.com/releases/2007/01/070123162031.htm
Gastrointestinal graft-vs.-host disease is a common and potentially deadly side effect for patients who undergo an allogeneic stem-cell transplant to treat certain blood cancers. Now, new research from Fred Hutchinson Cancer Research Center shows that adding a widely used topical corticosteroid to the standard treatment for GVHD kept the disease in remission and significantly reduces deaths one year after therapy.
A reformulation of beclomethasone dipropionate (BDP) into two different pills specifically releasing the drug into the stomach and mid-small intestine prevented relapse of gastrointestinal GVHD and allowed those patients to be on a shorter treatment course of high-dose prednisone. Mortality was reduced by 46 percent a year following the start of treatment in a multi-center Phase III clinical trial, according to findings published today in the online edition of the journal Blood. The lead author is David M. Hockenbery, M.D., a member of the Clinical Research Division at the Hutchinson Center and a professor of medicine/gastroenterology at the University of Washington School of Medicine. BDP is an anti-inflammatory drug long used to treat a variety of diseases such as asthma and ulcerative colitis.
About 60 percent of patients who receive an allogeneic stem-cell transplant to treat blood cancers such as acute and chronic myelogenous leukemia, acute lymphocytic leukemia and non-Hodgkin's lymphoma develop gastrointestinal GVHD as a major side effect of being infused with donor stem cells. Those who show gastrointestinal symptoms of the disease usually receive a two to four-week course of high-dose systemic prednisone therapy that is then tapered slowly. However, that drug is a two-edged sword, Hockenbery said. On the one hand it is designed to suppress the donor cells so GVHD can be controlled. But suppressing the immune system also makes patients susceptible to potentially fatal infections.
In the clinical trial, 129 patients were randomized into two groups. One group received a short course of standard prednisone therapy and oral BDP for 50 days. The other group received a placebo in place of the oral BPD for the same period. At day 10, the prednisone dose was quickly tapered in patients whose symptoms had responded. Fewer patients randomized to BDP had a subsequent flare-up of GVHD. After completion of the 50-day treatment period, patients were followed for an additional 30 days to see if the treatment effect would last. Patients randomized to BDP had a significantly more durable response rate compared to those in the placebo group. At one year after treatment, mortality rates had been reduced 46 percent compared to the placebo group.
"Oral BDP provides much more tailored and targeted control of gastrointestinal GVHD and it allows patients to move away from the side effects of standard prednisone therapy. All of this improves the chances that patients will have a successful outcome," Hockenbery said. "I think this is a very convincing clinical trial because by targeting topical therapy to the areas most affected, we were able to keep symptoms at bay while minimizing systemic immune suppression."
The idea to reformulate BDP into an oral form for stem-cell-transplant patients belongs to George B. McDonald, M.D., one of the study co-authors and a colleague of Hockenbery's at the Hutchinson Center. McDonald, also a member of the Center's Clinical Research Division and a professor of medicine/gastroenterology at UW, initiated the early trials of oral BDP with funding from a U.S. Food & Drug Administration Orphan Products Development Grant. The goal was to target corticosteroid therapy to the areas of the GI tract affected by GVHD. The anti-inflammatory actions of the two BDP-containing pills would then be focused on the intestinal lining from top to bottom to suppress GVHD, thus avoiding excessive corticosteroid medication in the bloodstream.
The FDA is expected to decide whether to approve use of the oral form of the drug by July. If approved, it would be only the second drug approved by the FDA for treatment of GVHD in stem-cell transplant recipients.
The pivotal clinical trial was funded by an Orphan Products Development Grant of the U.S. Food & Drug Administration and by Enteron Pharmaceuticals Inc., a wholly-owned subsidiary of DOR BioPharma Inc. Fifteen other centers in the U.S. and France participated in the study. (Conflict of interest disclosure: George McDonald, M.D., is a consultant for Enteron Pharmaceuticals Inc. and has an equity position in the company.)
article on the study written by reuters health
http://www.cancerpage.com/news/article.asp?id=10524
Beclomethasone Improves Survival of Gastrointestinal Graft-v-Host-Disease
NEW YORK JAN 23, 2007 (Reuters Health) - Gastrointestinal graft-versus-host-disease (GVHD) is a common problem among patients undergoing allogeneic hematopoietic cell transplant, but now new research suggests that oral beclomethasone dipropionate (BDP) can help prevent disease relapses and improve survival.
In nasal spray and inhaler formulations, BDP is used to treat allergic rhinitis and asthma, respectively. New research suggests that in an oral, locally acting formulation, the corticosteroid is also an effective agent for gastrointestinal GVHD. Oral BDP is currently under review by the US Food and Drug Administration for this indication.
In a phase III trial, Dr. David M. Hockenbery, from the Fred Hutchinson Cancer Research Center in Seattle, and colleagues assessed the outcomes of 129 patients with gastrointestinal GVHD who were randomized to receive 50 days of oral BDP (8 mg/day) or placebo. All patients also received 10 days of prednisone.
Prednisone was rapidly tapered beginning at day 10 in patients with control of their GVHD symptoms, according to the report released Tuesday in the journal Blood. Patients without control at day 10 were considered treatment failures and the study drug was discontinued.
On intention-to-treat analysis, oral BDP was associated with 37% and 45% reductions in the risk of GVHD-treatment failure at study day 50 and at 30 days follow-up, respectively. The corresponding risk reductions among patients eligible for the prednisone taper at day 10 were 61% and 62%.
By day 200 after transplantation, 5 BDP-treated patients had died compared with 16 control patients, a risk reduction of 67% (p = 0.03). The reduction in mortality risk with BDP was even more pronounced among subjects who had received unrelated and HLA-mismatched stem cells -- 91% (p = 0.02). The survival benefit was still apparent 1 year after randomization.
The study was supported, in part, by Enteron Pharmaceuticals, a subsidiary of DOR BioPharma, the Miami-based company that is developing oral BDP under the trade name orBec.
SOURCE;
Blood 2007;109.
UPI article on the data published in Blood
the articles posted about the drug have burried the name dor and none have used the symbol. That is why it hasn't helped the stock more
Analysis: An unlikely use for asthma drug
By ED SUSMAN
WASHINGTON, Jan. 25 (UPI) -- A drug used to treat patients with asthma also appears to combat often deadly graft-versus-host-disease, a frequent serious complication of bone-marrow transplants undertaken to cure people with leukemia and other diseases, researchers said Thursday.
Doctors at the Fred Hutchinson Cancer Research Center in Seattle said that treating patients with beclomethasone dipropionate in an experimental two-capsule formulation reduced the mortality of patients with graft-versus-host-disease by 67 percent in a phase 3 clinical trial.
"People with graft-versus-host-disease are caught between a rock and a hard place," said David Hockenbery, professor of medicine at the University of Washington and a member of the Hutchinson medical faculty.
The disease itself indicates the new donor blood transplant is working to eradicate remaining cancer cells in the blood, but at the same time the disease is destroying healthy tissues in the stomach and small intestine, Hockenbery told United Press International.
Doctors treat graft-versus-host-disease with high doses of the systemic steroid prednisone, but that has its own galaxy of dangerous side effects, including a tendency to weaken the immune system and make patients with already compromised immune systems even further at risk from serious opportunistic bacterial and fungal infections that can also be lethal.
Writing in the current online issue of Blood, the journal of the Washington -based American Society of Hematology, Hockenbery and colleagues described use of the investigative formulation of beclomethasone. One tablet dissolves in the stomach, while the second tablet is enteric-coated, so it survives the stomach and dissolves in the small intestine.
"Although graft-versus-host disease can affect the skin and the liver and other parts of the body, most of the time it attacks the gut," Hockenbery explained. The experimental formulation -- called Orbec and being developed by DOR BioPharma in Miami, acts as a topical steroid, he said. It coats the stomach and the small intestine and protects those organs from graft-versus-host-disease.
In the clinical trial, researchers from across the United States recruited 129 patients with graft-versus-host-disease following bone marrow transplant procedures and first gave them prednisone for 10 days to acutely control the disease, and then were rapidly tapered off the drug.
Then, 62 patients were given oral beclomethasone, while another 67 patients were given placebo in a 50-day treatment course.
After six months following the start of the trial, five of the patients on beclomethasone had died, compared with 16 patients taking placebo -- a 67-percent reduction in mortality, Hockenbery said. Even more encouraging was that survival benefit continued for at least a year, he reported.
Hockenbery said that Orbec is under review by the Food and Drug Administration.
"This treatment looks pretty exciting," Susan Stewart, executive director of the Blood & Marrow Transplant Information Network, a patient advocacy and information group, told UPI.
"When it comes to graft-versus-host-disease, patients are faced with, 'Which devil do you want to choose?' -- the destruction of your tissues by the disease or the side effects of prednisone, which is the 'moon-faced' effect that occurs very rapidly when taking the drug and the high risk of serious infections," she said.
"This drug offers a better choice, and will likely change clinical practice if it receives FDA approval," Stewart said.
About 20,000 people a year in the United States undergo bone-marrow transplantation for curative treatment of blood cancers such as leukemia, lymphoma and multiple myeloma, said Stewart, who is a long-term survivor of leukemia and a bone-marrow transplant.
Bone-marrow transplantation is also used to treat patients with hereditary immune disorders such as severe combined immunodeficiency disorder -- the so-called "Bubble Boy" disease -- sickle cell anemia, severe aplastic anemia and other rare disorders.
Stewart said about half the patients who undergo bone-marrow transplant receive their own blood cells and only rarely suffer graft-versus-host-disease, but the risk of the disease is about 60 percent in patients who receive blood marrow transplants from other people, usually closely related relatives.
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