SCYNEXIS’s lead drug candidate, SCY-635, is in Phase 2 development. The candidate successfully completed Phase 1b proof-of-concept studies in patients chronically infected with genotype 1 hepatitis C virus (HCV), the most prevalent and most difficult to treat genotype in North America.
SCY-635 Study Results:
In the 15-day, single-agent Phase 1b study a mean 2.3 log10 reduction was achieved at day 15. All patients in the highest dose cohort experienced viral load reductions within 12 to 24 hours of initiating treatment. There were no significant adverse events, discontinuations or drug-related toxicities and, importantly, the study demonstrated little to no selection of resistant virus after 15 days of monotherapy, suggesting a high genetic barrier to resistance. Subsequently, SCYNEXIS has demonstrated that the hepatitis C virus requires multiple mutations across two separate proteins in order to establish resistance to SCY-635 in in vitro studies. The majority of HCV drugs on the market and in development require only one targeted viral mutation to establish resistance.
Additional 2-drug combination in vitro studies of SCY-635 in combination with non-nucleoside polymerase inhibitors, nucleoside polymerase inhibitors, protease inhibitors (boceprevir and telaprevir), ribavirin and interferon alpha 2b each demonstrated additive-to-synergistic antiviral activity. Importantly, SCY-635 did not increase cell cytotoxicity associated with this wide range of mechanistically diverse anti-HCV agents. The observation of additive-to-synergistic antiviral activity suggests that clinical evaluation of combination therapy with SCY-635 could play an important role in advancing the HCV treatment landscape.
Phase 2 Study Design:
The current Phase 2a clinical trial is a 28 day study in treatment-naïve patients chronically infected with genotype 1 HCV. Escalating doses of SCY-635 in combination with PEG-interferon and ribavirin (PEGASUS®) are being studied. The primary end-point of the study is the rapid virological response (RVR) rate or percentage of patients who achieve undetectable plasma HCV RNA after 28 days of treatment. Top line results are anticipated in H1 2011.
About HCV and Therapeutic Need
The World Health Organization estimates that about 3% of the world’s population is infected with HCV and that there are more than 170 million chronic carriers who are at risk of developing liver cirrhosis and/or liver cancer. There are currently only two drug classes approved to treat HCV, interferons and ribavirin, which are typically used in combination as the standard of care. However, this approach has been shown to be effective in fewer than 50% of cases of HCV genotype 1—the most common genotype in North America. Resistance issues, serious side effects, including black box labeling, and a significant population of patients who are contraindicated or otherwise difficult to treat have created an urgent demand for new anti-HCV agents.
Because SCY-635 affects a new target—cyclophilin—and represents a new mechanism of action to treat HCV, SCYNEXIS believes that SCY-635 may become an important new addition to the HCV treatment landscape.
Core SCY-635 Facts
- Inhibits host cyclophilin A, a mechanism shown to completely suppress viral replication in vitro
- Exhibits additive-to-synergistic anti-viral activity with the standard of care and with therapies under development
- Has demonstrated a high genetic barrier to resistance; studies suggest SCY-635 will not exhibit cross resistance to investigational therapies such as protease and polymerase inhibitors