Gone for good.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Thurly, is this it? Total failure.
Pfizer, J&J report ominous PhIII failure of bapineuzumab in Alzheimer's study
July 23, 2012 | By John Carroll
Pfizer ($PFE) and Johnson & Johnson ($JNJ) are reporting that in the first of four Phase III trials, bapineuzumab failed to outperform a placebo in moderating symptoms of mild-to-moderate Alzheimer's, a clinical train wreck that will only raise further doubts about the R&D track they laid down.
Investigators had gambled heavily on the belief that an IV formulation of the drug could help a group of patients who shared the ApoE4 (apolipoprotein E epsilon 4) genotype, one of four studies Pfizer and J&J's Janssen had divided between them. With the failure the companies are slamming the brakes on dosing patients in an extension study of this particular Phase III trial, though they will continue to be evaluated. The other three trials are expected to read out soon.
Pfizer didn't detail the results from the study, but a failure to register significant improvements over a placebo on two co-primary endpoints--a change in cognitive and functional performance--bodes ill for one of the most closely watched late-stage programs of the year. Elan, which retained a revenue stake in their licensing pact, is likely to be part of the collateral damage today. It also is likely to cast a long shadow over Eli Lilly's ($LLY) solanezumab, which analysts believe has an even lower likelihood of success.
Read more: Pfizer, J&J report ominous PhIII failure of bapineuzumab in Alzheimer's study - FierceBiotech http://www.fiercebiotech.com/story/jj-pfizer-report-ominous-phiii-failure-bapineuzumab-alzheimers-study/2012-07-23#ixzz21VT0IQWU
Thorpe and Shan deliver talks at the IBC 10th Annual Antibody Therapeutics meeting in San Diego, Dec 5, 2012.
http://www.ibclifesciences.com/antibodyeng/agenda-ther.xml
Development Status of Immunomodulatory Therapeutic Antibodies
8:00
Chairperson's Opening Remarks
Philip E. Thorpe, Ph.D., Professor of Pharmacology and The Serena S. Simmons Distinguished Chair, University of Texas Southwestern
11:00
Overcoming Immune Suppression in Tumors with Bavituximab: Preclinical Studies
Bavituximab is a monoclonal antibody that is proving safe and effective as a second-line therapy in advanced lung cancer patients. It targets the immunosuppressive lipid, phosphatidylserine, which becomes exposed on tumor blood vessels and tumor cells. Bavituximab causes MDSCs to differentiate into tumoricidal M1 macrophages that destroy the tumor vasculature and tumor cells by ADCC. It also causes immature dendritic cells in tumors to mature and present tumor antigens, resulting in the generation of tumor-specific cytotoxic T-cells.
Philip E. Thorpe, Ph.D., Professor of Pharmacology and The Serena S. Simmons Distinguished Chair, University of Texas Southwestern
11:30
Clinical Development of Bavituximab, a Phosphatidylserine (PS)-Targeting Monoclonal Antibody
Bavituximab, an investigational monoclonal antibody, localizes selectively on tumor vasculature, synergizes with chemotherapy, causes vascular shut down in tumors and reactivates innate and adaptive tumor immunity. In clinical trials to date, bavituximab has been well-tolerated both as a single agent and in combination with approved therapies. Bavituximab has demonstrated promising anti-tumor activity as an adjunct to standard chemotherapy in several solid tumor indications and is advancing to late-stage clinical development in non-small cell lung cancer.
Joseph Shan, MPH, Vice President, Clinical and Regulatory Affairs, Peregrine Pharmaceuticals, Inc.
RRdog, after listening a few times I was surprised that the first time I had missed the stuff about exosomes.
At least one of the missing slides was about exosomes. Thorpe does talk about PS on exosomes and how
blocking that is another way to reduce immunosuppression. I am looking forward to the paper on
awakening the immune system with bavi that must be on the way. Is there a way I can send you something?
Entdoc, I am not sure that their immune systems are in such bad shape. Rather their immune systems are very
suppressed. That is one of the beauties of the bavi treatment. In the NYAS lecture Thorpe talks a lot about the
M2 to M1 switch of macrophages done directly by bavi, and all the other changes in the tumor microenvironment.
Since then there was a paper which showed the same switch happens with neutrophils, something never mentioned
before. It truly is a new paradigm for cancer treatment. I have been saying for a while that the immune system
is all that you need to defeat cancer. Well this is a good start!
I think all this talk about hazard ratios is just another red herring, more obfuscation.
This is a good introduction. You can skip over the math.
http://www.medicine.ox.ac.uk/bandolier/painres/download/whatis/what_are_haz_ratios.pdf
I think the slides that were not shown on the NYAS webcast may be in a paper under review, the same could
be true of a few slides from Thorpe's Barcelona keynote presentation. Just my guess.
Yes, I hadn't thought of that. A deal with one BP for USA for any indication they want to pursue, and another deal
with a different BP for Europe for any indication, another BP for Asia. Would that work? That would allow the BP
to pursue the indication more important for their region. For example in Asia liver cancer is much bigger than in USA.
I found that I have the whole 53-page PDF. The other 35-page PDF is I believe from Thorpe's talk at
IBC’s 22nd Annual Antibody Engineering
and 9th Annual Antibody Therapeutics
International Conferences and the
2011 Annual Meeting of The Antibody Society,
December 5–8, 2011, San Diego, CA
he is again giving a talk at the same meeting this year.
I have 35 of the slides, mostly missing those at the beginning, in a PDF file if you want it.
CJ, when I click on this link in the info box I get an error message.
...A few of the more illustrative slides from Dr. Thorpe's 5-26-11 talk: http://tinyurl.com/3m33h33 . . .PT's entire 53-pg PDF: http://tinyurl.com/3ck56gr
The PDF is from Thorpe's Barcelona talk last year. Many of the slides were also in the NYAS talk,
including I believe some of the slides Thorpe had withdrawn, although he described them on the audio.
Because it would be illegal. You can only sell it for approved indications.
median is half have died, mean is the average.
Entdoc, I think too much is made of this. Rituximab is a chimeric mAb that was approved 15 years ago
and is still going strong. It gained approval two years ago for maintenance therapy for follicular lymphoma.
http://en.wikipedia.org/wiki/Rituximab
I think if bavi + docetaxel is actually working to stop metastasis, as it seems to be doing in second-line NSCLC,
it is working against small tumors already. I think what is going on is that the primary tumors are stable and
the treatment is preventing the small tumors which start in other organs from growing into larger tumors.
The committee for the medicine prize is a lot different than the committee for the "peace" prize. I think they regret it now.
Yes, it will take years to validate the preclinical data in humans. People might nominate him, but there
will have to be much more evidence before he could get the prize. Also, and very importantly for
scientists, the MOA needs to be proven beyond a doubt.
Yes, but it will be years before that happens.
Really the problem is not for the first BP which would license for NSCLC, but trying to make a deal after
that for say pancreatic cancer, or anything else. If a deal were made for the whole platform then the BP
could push parallel phase 3 trials on several indications as quickly as possible. That would take a lot of money.
That approach is what Genentech did with Avastin. On the other hand if the potential is big enough maybe the
second licensee wouldn't mind too much. We have gone over this before, how can you even come up with a
reasonable price if you are making a deal for the whole platform, and one that some BP could actually afford?
How about a milestone type approach? For every additional indication approved the BP pays more to Peregrine?
That way the total keeps getting bigger but the BP only has to pay as the money comes in. Or one big
payout to start and a good global royalty rate for all sales would accomplish the same thing. Like $10 billion up
front and 15% royalty on all future sales? I could accept that.
There is a distinction that could be made. The deal could be for cancer only. That would give Peregrine
plenty of money for research on anti-viral, bacterial, parasitic uses of anti-PS. Those uses could also be very
large but will take time to develop. I would favor that too. I guess my concern is that there would be uses
that would never get tried because one BP just would not have the resources to push research and
development across the whole range of possible uses.
Mojojojo, I hadn't really given this much thought before. But, you definitely have a point. The problem arises
because of the existence of a drug that has a realistic chance to work on many cancers. A pan-cancer treatment.
When these guidelines were adopted nothing like that was on the horizon. Avastin was the first biologic drug that
worked on several different cancers, but it hasn't turned out to have the wide use that was first thought.
However, there are many chemo drugs that are used on many different cancers. Docetaxel for example.
I think the difference here is the potential uses with bavituximab are much bigger. So is it possible to
keep the uses of bavituximab under control? Of course cancer patients don't care about that, nor would a BP
that had a license for NSCLC, if it wasn't against the FDA rules, they would be happy to sell as much as possible.
There is one thing that might help here. Bavituximab is only made by Avid, the sole supplier. Would it be possible
for Avid/Peregrine to control the flow of bavi to only NSCLC patients? I know that any doctor is suppose to be free
to prescribe any approved drug for what uses he/she deems it useful for, but maybe some new rules need to be made.
If only oncologists can prescribe it, and they would have to certify that it is only for use with NSCLC in writing, maybe
that would work. As it is now the doctors don't care because it is the BP that suffers for selling the drug for off-label use.
I know the doctors will all be against this so it probably won't work, but I don't know what else would work. This will
become a more visible problem if by the end of the year there is good data from the pancreatic and liver cancer trials.
What is going on with bavi + docetaxel? Why is there such an increase in the MOS of the treatment arms?
This is truly a breakthrough. It was seen before in mice with breast cancer treated with bavi + docetaxel.
A monoclonal antibody that binds anionic phospholipids on tumor blood vessels enhances the
antitumor effect of docetaxel on human breast tumors in mice.
Huang X, Bennett M, Thorpe PE.
Cancer Res. 2005 May 15;65(10):4408-16.
FREE: http://cancerres.aacrjournals.org/content/65/10/4408.long
This image is from that paper. It shows the tumor colonies that have formed in the lungs after the breast
cancer became metastatic. Note the bar chart with the 3G4 + doc column showing that 5/10 mice had
zero tumor colonies in the lungs. This is what I think is happening to the patients in the second-line NSCLC trial.
Bavi + docetaxel has greatly reduced the metastasis in these patients and so they are not dying as quickly,
or maybe some of them are cured. Note 3G4 is the mouse version of bavituximab.
Another thing that is amazing is that the mouse models are predictive of the human results. I think this is
because bavi works with the immune system in a very basic way which is common to both mouse and human.
There is another positive. If the second-line NSCLC MOS data is as strong as it looks to be then
the size of the phase III trial won't have to be that large. Maybe only 2-3 times the size of the phase II trial,
especially as there will likely only be one bavi dose arm. That means it will take less money and so
Peregrine can retain more of its leverage.
Yes, I just listened to it again. It is amazing. Did anyone else notice that one of the organizers and the
introductory remarks were given by George Zavoico an analyst at MLV & Co.?
CJ, I want to thank you for the incredible effort you have put into this board. I don't think we thank you often enough.
I think they were results that have not been published yet, might be in a submitted paper under review.
I think some of them may have been shown in previous talks.
I disagree that, in this case, the partner will be the one designing the phase 3 trial. Peregrine has said
that the phase 2 trial was designed to be the best possible and that the phase 3 will just be a scaled up
version of the phase 2. This gives Peregrine an advantage when negotiating with a big pharma company
and the FDA. The whole thing can be ready to go ahead once a deal is made thus reducing the time needed
to start the phase 3. Mostly I think what is needed is money for the expanded number of clinical sites
that will be necessary for the phase 3. They will also need more manpower for the increased amount of record
keeping and preparing the package for approval.
The Time article obviously refers to all patients diagnosed with rectal cancer, so at all stages, whereas
the PR is referring only to patients with stage IV (metastatic) rectal cancer.
Onyx Pharmaceuticals Receives FDA Accelerated Approval of Kyprolis™ (carfilzomib) for Injection
South San Francisco, CA. — Jul. 20, 2012
Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval of Kyprolis™ (carfilzomib) for Injection, a proteasome inhibitor, indicated for the treatment of patients with multiple myeloma who have received at least two prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of completion of the last therapy. The indication for Kyprolis is based on response rate. Currently, no data are available for Kyprolis that demonstrate an improvement in progression-free survival or overall survival.
“Today’s approval is a significant milestone for Onyx and, most importantly, for patients with advanced myeloma who have few treatment options available to them,” said N. Anthony Coles, M.D., President and Chief Executive Officer of Onyx Pharmaceuticals. “We deeply appreciate the hundreds of patients who participated in the Kyprolis clinical studies that led to this accelerated approval, and recognize the many clinicians across the country and researchers here at Onyx for their dedication in bringing this promising new medicine to patients. We are committed to continuing the clinical development of Kyprolis across earlier stages of multiple myeloma treatment.”
The approval was based on the results of the Phase 2b 003-A1 study, a single-arm, multicenter clinical trial that enrolled 266 patients with multiple myeloma, who had received a median of five prior anti-myeloma regimens. The primary efficacy endpoint was overall response (ORR) and determined by an Independent Review Committee using the International Myeloma Working Group (IMWG) criteria. ORR was 22.9% and median response duration was 7.8 months.
Safety data were evaluated in 526 patients with relapsed and/or refractory multiple myeloma who received single-agent carfilzomib. There were 37 deaths on study, or 7% of patients. The most common causes of death, other than disease progression, were cardiac (5 patients), end-organ failure (4 patients), and infection (4 patients). Important warnings and precautions include cardiac arrest, congestive heart failure, myocardial ischemia; pulmonary hypertension, pulmonary complications, infusion reactions, infusion reactions, tumor lysis syndrome, thrombocytopenia, hepatic toxicity and embryo-fetal toxicity. The most common serious adverse reactions were pneumonia, acute renal failure, pyrexia, and congestive heart failure. The most common adverse reactions (incidence of 30% or greater) observed in clinical trials of patients with multiple myeloma were fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, and pyrexia. Serious adverse reactions were reported in 45% of patients.
.....
Enrollment has been completed for the Phase 3 confirmatory clinical trial, known as the ASPIRE trial. The company has an agreement with the FDA on a Special Protocol Assessment (SPA) for this trial.
Thanks to Adam "F**k Head" Feuerstein I just bought some more shares of PPHM cheaper than I thought I could.
As someone said, two smear attacks in a week shows the desperation of the shorts. AF must be a secret
shorter, or is being paid off. Just more of the corruption and fraud we have come to expect from Wall Street.
Loofman, here is St Peregrine, well a plastic version, who has stopped by your shack to sprinkle
some Korn Licker (Holy Water) on your shack to give you luck in your Peregrine investments. However,
old St. Peregrine would like a cut of all that money you will be making. Say 5%? You know, for all the
good deeds he has done, that's fair isn't it? Besides, he has some insider info on that second-line trial data,
he'll know before anyone else when the MOS is triggered. He gets real-time updating.
FF, it has now been 10.5 months since the last patient enrolled in the first-line trial.
I hope the control arm MOS is about 9 months and the treatment arm ends up at 13.5 months
(50% improvement), but I thought that before with the second-line trial and here
we are at what might be a 100% improvement.
FF, the comparison trial that Peregrine used for the first-line signal seeking
trial was the Sandler et al 2006 paper listed in the tables. That trial was
Avastin + CP and had MOS = 12.3 months, PFS = 6.2 months, and ORR = 35%.
FF, my post # 81841 gives the treatment arms for the 12 first-line trials, and
the control arms for the same trials are in post # 81830, and they all are using CP.
There was one piece of information missing from the JMP conference and the quarterly conference
call that I wanted to hear. That is, has the control arm MOS for the first-line NSCLC trial been triggered?
Nothing, which I assume means that it has not been triggered. Could it be that this control group is
relatively healthy? Assuming the the arms are well balanced then it might be quite a while before we know
much more about that trial.
biopharm you missed it, post # 83316.
RRdog, won't that automatically make bavi + docetaxel the first-line treatment of choice? Oncologists
would start using it without phase 3 trial results for first-line if bavi + doce gets accelerated approval for
second-line. What about other cancers? Nothing to stop oncologists from trying it on just about any second-line cancer.
Okay, I'll play along. 3 months from today is Oct 18. I am guessing that the second-line MOS will be released by then.
My guesses are:
1. $2 - 100%
2. $5 - 75%
3. $10 - 25%
4. $20 - 0%
The law does not have to change. Medicare will simply reduce the amount of money they
will reimburse for treatments and everyone will have to adjust to that reality.
I'll second that!
Mojojojo, I am sure that Bavi will be one of the best drugs ever as far as clinical benefit to cost is concerned.
I was just pointing out that in the next decade the pricing of treatments will likely have to decrease because of
budgetary considerations. Medicare spending, in total not just for cancer, is rising by at least 7% a year which
means in 10 years it will double to almost $1 trillion. That is only for Medicare, clearly this is unsustainable.
That is all I have to say on this topic.
Here is the follow up article.
Projections of the Cost of Cancer Care in the United States: 2010–2020
Angela B. Mariotto, K. Robin Yabroff, Yongwu Shao, Eric J. Feuer, Martin L. Brown
Correspondence to: Angela B. Mariotto, PhD, Surveillance Research Program, Division of Cancer Control and Population Sciences,
National Cancer Institute, Ste 504, MSC 8317, 6116 Executive Blvd, MSC 7344, Bethesda, MD 20892-7344 (e-mail: mariotta@mail.nih.gov).
Background Current estimates of the costs of cancer care in the United States are based on data from 2003 and earlier.
However, incidence, survival, and practice patterns have been changing for the majority of cancers.
Methods Cancer prevalence was estimated and projected by phase of care (initial year following diagnosis, continuing,
and last year of life) and tumor site for 13 cancers in men and 16 cancers in women through 2020. Cancer prevalence
was calculated from cancer incidence and survival models estimated from Surveillance, Epidemiology,
and End Results (SEER) Program data. Annualized net costs were estimated from recent SEER–Medicare linkage
data, which included claims through 2006 among beneficiaries aged 65 years and older with a cancer diagnosis.
Control subjects without cancer were identified from a 5% random sample of all Medicare beneficiaries residing
in the SEER areas to adjust for expenditures not related to cancer. All cost estimates were adjusted to 2010
dollars. Different scenarios for assumptions about future trends in incidence, survival, and cost were assessed
with sensitivity analysis.
Results Assuming constant incidence, survival, and cost, we projected 13.8 and 18.1 million cancer survivors in 2010
and 2020, respectively, with associated costs of cancer care of 124.57 and 157.77 billion 2010 US dollars. This
27% increase in medical costs reflects US population changes only. The largest increases were in the continuing
phase of care for prostate cancer (42%) and female breast cancer (32%). Projections of current trends in incidence
(declining) and survival (increasing) had small effects on 2020 estimates. However, if costs of care
increase annually by 2% in the initial and last year of life phases of care, the total cost in 2020 is projected to be
$173 billion, which represents a 39% increase from 2010.
Conclusions The national cost of cancer care is substantial and expected to increase because of population changes alone.
Our findings have implications for policy makers in planning and allocation of resources.
J Natl Cancer Inst 2011;103:1–12
I would say the 2% increase is way too low.
Biopharm and Mojojojo, that is my point. The population of age 65 and over is increasing as us baby boomers age.
The 65 and over population has the highest incidence of cancer. The Medicare budget is not going to be able
to handle the big increase in costs because of this and other costs associated with getting older,
like heart disease, Alzheimers, etc. Not to mention the ongoing budget deficit. Something has
got to give and I think that means the huge costs of cancer treatment will have to come down.
It may be in line with current prices, but I am saying that won't last. I would just use a lower estimate.
I am just trying to be realistic. There will still be plenty of money made because of all the possible indications.