Replies to post #105557 on Biotech Values

[biomaven0]

Here's another abstract w/ more detail:

ID#
806

Location:
Hynes: Exhibit Hall C

Time of Presentation:
Oct 31 8:00 AM - 5:30 PM

Category:
R05. HCV: Clinical Trials and Therapeutic Developments




High Rapid Virologic Response (RVR) with PSI-7977 QD plus PEG-IFN/RBV in a 28-day Phase 2a Trial
E. Lawitz4; J. P. Lalezari5; M. Rodriguez-Torres8; K. V. Kowdley7; D. Nelson3; E. DeJesus6; J. G. McHutchison2; M. Mader1; E. Albanis1; W. Symonds1; M. Berrey1
1. Clinical Development, Pharmasset, Inc, Durham , NC, United States.
2. DCRI, Durham, NC, United States.
3. University of FL, Gainesville, FL, United States.
4. Alamo Medical Research, San Antonio, TX, United States.
5. Quest Clinical Research, San Francisco, CA, United States.
6. Orlando Immunology Center, Orlando, FL, United States.
7. Virginia Mason Medical Center, Seattle, WA, United States.
8. Fundacion de Investigacion de Diego, Santurce, PR, United States.



PSI-7977 is a novel nucleotide analog in development for HCV.
Methods: 63 treatment-naïve non-cirrhotic patients infected with HCV genotype 1 (GT-1) were enrolled at 7 sites in the US. Patients were stratified by IL28B status (C/C vs any T allele) into 4 cohorts: PSI-7977 100mg, 200mg, 400mg QD or matching placebo with SOC for 28 days.
Results: Treatment groups were well-balanced for age, race, BMI, baseline HCV RNA (~6.5 log10 IU/mL), and HCV GT 1a vs 1b. Significant and consistent antiviral activity was observed following 28d of PSI-7977/SOC with no on-treatment viral breakthrough. 16 patients receiving PSI-7977 100mg QD/SOC achieved 88% (14/16) Rapid Virologic Response (RVR), or HCV RNA below the limit of detection (<15 IU/mL). 18 patients receiving PSI-7977 200mg QD/SOC achieved 94% (17/18) RVR. One patient who received 200mg QD was lost to follow up at D14 after a 4.7 log10 decline in HCV RNA. 15 patients receiving PSI-7977 400mg QD/SOC achieved 93% (14/15) RVR. 14 patients received placebo/SOC and 21% (3/14) achieved RVR. There were no differences in response for HCV GT 1a vs 1b. After discontinuation of PSI-7977, no rebound in HCV RNA was detected in any patient who received PSI-7977 200mg QD/SOC through week 8. Of the 14 patients who received PSI-7977 400mg QD/SOC and achieved RVR, 12 remained below LOD at week 8. Preliminary safety and tolerability for the 28 day treatment period were similar for PSI-7977/SOC and placebo/SOC. There were no serious adverse events (SAEs) reported, and no adverse events (AEs) led to treatment discontinuation. A majority of AEs reported were mild intensity. AEs reported were similar to clinical experience with SOC. There were no dose-related changes in safety laboratory assessments, vital signs or ECGs. A dose-dependent decrease in serum ALT was observed coincident with HCV RNA decline.
Conclusions: PSI-7977 demonstrated potent short term antiviral activity with an RVR of 88-94% across all doses tested and was generally safe and well tolerated. All patients receiving active PSI-7977 demonstrated continuous declines in HCV RNA with no viral breakthrough during 28 days of therapy; a majority of subjects continued to have HCV RNA below LOD after discontinuation of PSI-7977. Data from this study support longer duration studies of PSI-7977.



Intent-to-Treat (ITT-last observation carried forward) RVR and week 8 HCV RNAStudy Arm

n Mean ? in HCV RNA
(log10 IU/mL) at Day 28 % of Patients with HCV RNA <15 IU/mL at Day 28 % of Patients with HCV RNA <15 IU/mL at Week
PSI-7977 100mg QD/SOC
16 -5.3 88% (14/16) 56% (9/16)
PSI-7977 200mg QD/SOC
18 -5.1 94%* (17/18) 94%* (17/18)
PSI-7977 400mg QD/SOC
15 -5.3 93% (14/15) 80% (12/15)
Placebo + SOC 14 -2.8 21% (3/14) 36% (5/14)
* one patient lost to follow up after week 2