Por Julie S. Hoggatt; julie.hoggatt@wolterskluwer.com / Leon Henderson; leon.henderson@wolterskluwer.com / Ben Weintraub; ben.weintraub@wolterskluwer.com.
Incivek (telaprevir) has set the bar for a minimum 70% SVR rate in treatment naïve patients and at most a 24-week regimen for the large majority of HCV patients. Although the challenge for pipeline DAAs is high, developmental compounds appear to have the potential to be favored over Incivek.
BMS-790052
On September 17, Bristol released data from a phase II study on its once-daily DAA, BMS-790052 plus Pegasys and ribavirin in 48 genotype 1, treatment naïve patients. At 24-weeks post treatment, 83% of treated subjects maintained SVR. Both the 10mg and 60mg arms had 83% SVRs, while the 3mg arm had a 42% SVR. This compared with 25% SVR in the placebo group. Adverse events (AEs) in the BMS-790052 arms were similar to the placebo arm. The most common AEs were anemia and nausea. Anemia occurred in 50% of the 60mg arm, 41.7% of the 10mg arm, and 41.7% of the control/placebo arm. Nausea occurred in 33.3% of the 60mg arm, 33.3% of the 10mg arm and 41.7% of the 3mg arm and 50% of the control/placebo arm. We are publishing our inThought Approvability Index (IAI) score on BMS-790052 as a 60%(A). Our 2018 US revenue estimate for 790052 is $447 million.
PSI-7977
In September, Pharmasset announced data from the PROTON trial studying once-daily PSI-7977 with Pegasys and ribavirin in genotype 1, treatment naïve patients. Data demonstrated an impressive 91% SVR. After a 24-week regimen incorporating 12-weeks of PSI-7977 400mg once daily, 43 of 47 patients demonstrated an SVR. Safety data are likely to be presented at AASLD in November. In July, Pharmasset announced PROTON trial data on genotypes 2 and 3. This arm studied a 12-week regimen of 400mg PSI-7977 once-daily with Pegasys and ribavirin. 24 out of 24 subjects achieved SVR 12-weeks after the completion of treatment.
INX-189
In September, Inhibitex announced that INX-189 has begun dosing in a 90-patient, phase II clinical trial. This study focuses on genotypes 2 and 3 patients using oncedaily INX-189 with Pegasys and ribavirin. 25mg, 50mg and 100mg treatment arms will receive a 12-week regimen. Treated patients with HCV RNA below the level of detection after 28 days and 12 weeks of dosing will stop all therapy. Those who do not qualify will receive Pegasys and ribavirin for another 12 weeks. The control arm will receive placebo plus Pegasys and ribavirin for 24 weeks. Inhibitex’s nucleotide inhibitor targets the RNAdependent RNA polymerase, NS5b, of HCV. It has high potential to be combined with oral protease inhibitors such as Incivek.
Revenue Forecast
Our revenue projections for the lead direct acting antivirals are depicted below. In our model, Incivek remains a component of first-line treatment. Our pricing for the pipeline direct acting antivirals shadows price for Incivek and Victrelis. In 2014, anew direct acting antivirals are likely to enter the U.S. market. Figures 1 and 2 show U.S. and worldwide (including U.S.) revenue forecasts for Incivek, 
Victrelis, TMC-435, BI 201335, Mericitabine (RG 7128), Danoprevir, Setrobuvir (ANA-598), VX-222 and Daclatasvir (BMS-790052). See Table 1 for description of the agents. In 2017, we expect an all oral regimen combining direct acting antivirals to become the new standard of care.
