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BMS-790052 is a First-in-class Potent Hepatitis C Virus (HCV) NS5A Inhibitor for Patients with Chronic HCV Infection: Results from a Proof-of-concept Study
R. Nettles1; C. Chien1; E. Chung1; A. Persson2; M. Gao3; M. Belema3; N. A. Meanwell3; M. p. DeMicco4; T. C. Marbury5; R. Goldwater6; P. Northup7; J. Coumbis8; W. K. Kraft9; M. R. Charlton10; J. C. Lopez-Talavera3; D. Grasela1
1. Research and Development, Bristol-Myers Squibb, Hopewell, NJ, USA.
2. Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA.
3. Research and Development, Bristol-Myers Squibb, Wallingford, CT, USA.
4. Advanced Clinical Research Institute, Anaheim, CA, USA.
5. Orlando Clinical Research Center, Orlando, FL, USA.
6. PAREXEL International, Baltimore, MD, USA.
7. University of Virginia, Charlottesville, VA, USA.
8. Research and Development, Bristol-Myers Squibb, Hamilton, NJ, USA.
9. Thomas Jefferson University, Philidelphia, PA, USA.
10. Mayo Clinic, Rochester, MN, USA.


BMS-790052 is a first in class and highly selective HCV NS5A inhibitor with in picomolar vitro potency against genotypes 1a and 1b. In a single ascending dose study with healthy subjects, BMS-790052 was shown to be safe, well tolerated, and had a pharmacokinetic profile suggestive of once daily dosing.
The objectives of this randomized, double blind, placebo-controlled, single ascending-dose study were to evaluate the safety, tolerability, antiviral effect and pharmacokinetics of BMS-790052 in patients with genotype 1 chronic hepatitis C (CHC). Patients were randomized to receive 1, 10, or 100mg of BMS-790052 or placebo (6 patients per dose; active:placebo=5:1) and could be treatment-naive or experienced men or women, 18 to 49 years of age with HCV RNA ≥105 IU/mL with non-cirrhotic compensated liver disease.
All BMS-790052 single doses were well tolerated and had a safety profile similar to that of placebo. Following oral administration, BMS-790052 was readily absorbed with dose proportional exposures over the studied dose range which were comparable to those observed in a previous study of healthy subjects. The mean terminal half-life of BMS-790052 was approximately 12 hours. The figure below shows the decline in HCV RNA for all doses from time of administration to 144 hours. Mean decline in HCV RNA 24 hours after a single 1, 10 and 100 mg dose of BMS790052 was 1.8 log10 (range 0.18 to 3.0 log10), 3.2 log10 (range 2.9 to 4.0 log10) and 3.3 log10 (range 2.7 to 3.6 log10), respectively. Furthermore, the 100 mg dose resulted in a mean decline of 3.6 log10 (range 3.0 to 4.1 log10) observed at 48 hours after dosing, which was maintained at 144 hours.
BMS-790052 is a potent NS5A inhibitor that produces a robust decline in HCV RNA following a single dose in patients chronically infected with HCV genotype 1. BMS-790052 was safe and well tolerated in single doses of up to 100 mg and has a pharmacokinetic profile that potentially supports once-daily dosing. Multiple dose trials are ongoing.