Replies to post #105550 on Biotech Values

[biomaven0]

Very good synergy w/ IFN/rRBV in a 28-day trial. Don't know if the same is true for all nucleotides or not.

ID#


1861

Location:


Hynes: Exhibit Hall C

Time of Presentation:


Nov 02 7:00 AM - 12:00 PM

Category:


R06. HCV Therapy: Preclinical and Early Clinical Development


Clinical synergy of an Anti-HCV Nucleoside Analog with SOC: Viral Kinetics of PSI-7977 with SOC
E. Lawitz1; J. P. Lalezari2; M. Rodriguez-Torres3; K. V. Kowdley4; D. Nelson5; E. DeJesus6; J. G. McHutchison7; A. De La Rosa8; W. Symonds8; M. Berrey8
1. Alamo Medical Research, San Antonio, TX, United States.
2. Quest Clinical Research, San Francisco, CA, United States.
3. Fundacion de Investigacion de Diego, Santurce, PR, United States.
4. Virginia Mason Medical Center, Seattle, WA, United States.
5. University of Florida, Gainesville, FL, United States.
6. Orlando Immunology Center, Orlando, FL, United States.
7. DCRI, Durham, NC, United States.
8. Pharmasset, Inc., Princeton, NJ, United States.


Background: PSI-7977 is a novel uridine nucleotide analog in development for the treatment of HCV which demonstrated a 0.5-2.0 log10 IU/mL decline in a 3-day monotherapy trial. Nucleoside/tide analogs: 1) require intracellular phosphorylation which may result in a slower initial antiviral decline in monotherapy assessments; 2) in vitro select for unfit resistant variants which do not seem to be readily present in the treatment-naïve viral population; and, 3) retain activity against HCV variants with resistance against other classes of antivirals. These characteristics are consistent and predictable, and clinically may be the explanation for the demonstrated potent antiviral activity in combination with alfa-interferon and/or DAA.
Methods: Sixty-three treatment-naïve non-cirrhotic patients infected with HCV genotype 1 (GT-1) were enrolled in a randomized study of PSI-7977 100mg, 200mg, 400mg QD or matching placebo, administered with PEG-IFN/RBV for 28 days. Based upon the 1.0 log10 antiviral decline of PSI-7977 200mg QD in the 3-day monotherapy study, we hypothesized that an additive effect in combination with Peg-IFN/RBV could be predicted by combining the monotherapy response with the observed HCV RNA decline in peg-IFN/RBV alone in the 28-day study.
Results: At study Day 3, subjects receiving placebo with Peg-IFN/RBV had demonstrated a 0.87 log10 IU/mL decline in HCV RNA. A reduction in HCV RNA greater than 1.87 log10 IU/mL [1.0 + 0.87 log10] was considered to be evidence of additive-to-synergistic antiviral activity. 18 patients receiving PSI-7977 200mg QD/SOC demonstrated a 3.3 log10 IU/mL decline at Day 3, or 1.43 logs greater than the anticipated additive antiviral activity of PSI-7977 200mg + Peg-IFN/RBV. 15 patients receiving PSI-7977 400mg QD/SOC demonstrated a 3.6 log10 IU/mL decline, or 0.78 logs greater than the anticipated 2.82 log10 IU/mL additive antiviral activity of PSI-7977 400mg + Peg-IFN/RBV [-1.95 + -0.87 log10 IU/mL]. No patient at any dose of PSI-7977 experienced a virologic breakthrough during the 28 days of drug administration.
Conclusions: PSI-7977 demonstrated greater-than-additive antiviral activity when combined with Peg-IFN/RBV. All patients receiving active PSI-7977 demonstrated continuous declines in HCV RNA, RVR rates of 88-94%, and no viral breakthrough during the 28 days of therapy. These data highlight the potential for a nucleotide-containing combination regimen to produce significant antiviral activity, the extent of which can not be predicted by monotherapy antiviral responses and support additional combination studies to be conducted in the future.

Actually I see now they have similar data on their website, including reductions at the 28 day mark:

http://www.pharmasset.com/pipeline/PSI-7851.asp

# Following 28 days of treatment with PSI-7977 200mg QD with Pegasys plus Copegus, patients achieved a mean 5.1 log10 IU/mL decrease in HCV RNA and 94% (17 of 18) achieved an RVR
# Following 28 days of treatment with PSI-7977 400mg QD with Pegasys plus Copegus, patients achieved a mean 5.3 log10 IU/mL decrease in HCV RNA and 93% (14 of 16) achieved an RVR
# Following 28 days of treatment with placebo with Pegasys plus Copegus, patients achieved a mean 2.8 log10 IU/mL decrease in HCV RNA and 21% (3 of 14) achieved an RVR

[WID]

CHICAGO, Oct 4 (Reuters) - Patients with the brain cancer glioblastoma treated with a vaccine lived nearly twice as long as those who received radiation and chemotherapy, an encouraging result for a cancer that often kills patients within a year, U.S. researchers said on Monday.

The Celldex Therapeutics Inc (CLDX.O) vaccine works by targeting a mutation in a gene called the epidermal growth factor receptor, which fuels cancer growth.

"It does appear to help patients live much longer than we could have expected," said Dr. John Sampson of Duke University in North Carolina, whose team worked on the study published in the Journal of Clinical Oncology.

Working with researchers at The University of Texas MD Anderson Cancer Center, Sampson's team showed the vaccine killed cancer cells carrying the mutation in all but one patient.

Immune response tests showed patients who developed antibodies after being vaccinated were most likely to respond, giving doctors a good way to see which patients might benefit, Sampson said in a telephone interview.

He said many patients in the study are still alive after five years. "That is pretty unusual with this disease."

Glioblastoma multiforme typically kills half its victims within a year and patients rarely survive more than three years. Sampson remains cautious and says the treatment still needs to be proven in a large-scale clinical trial.

CANCER IMMUNOTHERAPY

The finding is yet another example of the potential of cancer immunotherapies -- treatments that recruit the immune system to fight cancer.

Earlier this year, the U.S. Food and Drug Administration approved the first cancer vaccine, Dendreon Corp's (DNDN.O) prostate cancer therapy Provenge.

And a team in June said Bristol-Myers Squibb Co's (BMY.N) immune system treatment ipilimumab helped extend the lives of patients with aggressive melanoma, the deadliest form of skin cancer for which there are few treatment options.

For the midstage brain cancer study, researchers enrolled 35 people with glioblastoma who had undergone radiation and were treated with the chemotherapy drug temozolomide, sold by Merck (MRK.N) under the brand name Temodar, which is thought to boost immune response.

Of those, 18 people got the vaccine and 17 were in a control group. Those who got the vaccine lived an average of 26 months, compared with 15 months for those in the control arm.

Sampson said the vaccine is the first to target proteins only present in cancer cells, which could mean it would have fewer side effects than other cancer vaccines.

He said he has no current financial ties to Celldex, but has received research funding from the company in the past.

Epidermal growth factor receptor mutations are found in many other cancers, and the teams say the vaccine should be tested in other cancers as well. But funding the large studies it will take to prove the vaccine works may be a challenge.

Last month, Celldex's partner Pfizer Inc (PFE.N) pulled out of a strategic partnership to develop the vaccine, and the company said it now plans to develop it on its own.

The National Cancer Institute is spending $14 million over five years to develop a network of clinics to test cancer immunotherapy treatments. (Editing by Maggie Fox and Todd Eastham)

http://www.reuters.com/article/idCNN0413797320101004?pageNumber=1