October 11, 2012

Rapid and sharp decline in hepatitis C virus upon monotherapy with NS3 protease inhibitor, ACH-1625

Antivir Ther. 2012 Sep 13. doi: 10.3851/IMP2359. [Epub ahead of print]

Agarwal A, Zhang B, Olek E, Robison H, Robarge L, Deshpande M.


Achillion Pharmaceuticals, Inc., New Haven, CT, USA. aagarwal@achillion.com .

BACKGROUND: ACH-1625 is a linear peptidomimetic inhibitor that non-covalently binds to hepatitis C virus (HCV) NS3 protease with high potency and specificity. Short term monotherapy of HCV genotype-1 (GT-1) infection with ACH-1625 was found to be safe and resulted in ≥3.3 log(10) IU/mL mean viral load reduction. This viral load decay data was analyzed to compare HCV dynamics with prior reports and estimate the antiviral efficiency of ACH-1625.

METHODS: Drug efficiency (ε) was estimated by analyzing the viral decay following initiation of up to 5 days of monotherapy with ACH-1625 in 36 chronically-infected HCV GT-1 patients. During this monotherapy study, ACH-1625 was administered either twice a day for 4.5 days or once daily for 5 days at 5 different dose levels in 36 patients.

RESULTS: A sharp viral decay during first 48 hours following the initiation of ACH-1625 treatment afforded high drug efficiency estimates (≥ 0.9934). In addition, an increase in the estimated drug efficiency was observed with increasing ACH-1625 dose. The observed anti-HCV response was fairly uniform in this proof-of-concept study across the population of 36 patients.

CONCLUSIONS: Estimates of the treatment independent viral kinetics parameters were consistent with prior reports and the estimated drug efficiency of ACH-1625 monotherapy was very high (≥0.9934) in fasted and fed states.

PMID: 22976492 [PubMed - as supplied by publisher]


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