easl 2010 - oral presentations
TRANSCRIPT
-
8/9/2019 EASL 2010 - Oral Presentations
1/2
Oral Presentations
Session Title: Parallel Session: LATE-BREAKERS
Presentation Date: Apr 17, 2010
ONCE-DAILY NS5A INHIBITOR (BMS-790052) PLUSPEGINTERFERON-ALPHA-2A AND RIBAVIRINPRODUCES HIGH RATES OF EXTENDED RAPID
VIROLOGIC RESPONSE IN TREATMENT-NAIVEHCV-GENOTYPE 1 SUBJECTS: PHASE 2A TRIAL
S. Pol1, G. Everson2, R. Ghalib3, V. Rustgi4, C. Martorell5, H.A. Tatum6, J. Lim7, C.
Hezode8, U. Diva
9, P.D. Yin
9, R. Hindes
9
1Hpital Cochin, Paris, France, 2University of Colorado Denver & Hospital, Denver, CO,3The Liver Institute at Methodist Dallas Medical Center, Dallas, TX, 4Metropolitan
Research, Fairfax, VA, 5The Research Institute, Springfield, MA, 6Options Health
Research, Tulsa, OK,7Yale University School of Medicine, New Haven, CT, USA,
8CHU
Henri Mondor, Creteil, France, 9Bristol-Myers Squibb Company, Wallingford, CT, USA.*[email protected]
Background: BMS-790052 is a first-in-class, highly potent, once-daily HCV NS5A
inhibitor. In Phase I studies in HCV-infected subjects, BMS-790052 was well-tolerated and
exhibited potent antiviral activity.Methods: In this double-blind study, 48 subjects were randomized 1:1:1:1 to receive
placebo, 3 mg, 10 mg or 60 mg of BMS-790052, once-daily in combination with
peginterferon-alpha-2a and ribavirin (P/R) for 48 weeks in treatment-naive HCV genotype
1-infected subjects. The primary endpoint was the proportion of subjects with extended
rapid virologic response (eRVR) defined as HCV RNA < 10 IU/mL at both Weeks 4 and 12.
Results: Subject baseline and demographic characteristics were well-balanced across
treatment arms (n = 12/arm), with mean baseline HCV RNA 6.5 log10 IU/mL. The
proportion of subjects achieving eRVR was 42%, 83% and 75% in the 3 mg, 10 mg and 60
mg BMS-790052 + P/R arms, respectively, compared to 8% for P/R. Safety was
comparable across treatment arms (see table). Adverse events were consistent with those
commonly observed with P/R. Confirmed viral breakthrough was not observed in the 10mg and 60 mg BMS-790052 arms through Week 12.
Conclusions: BMS-790052 is a potent once-daily NS5A inhibitor that yielded higher
eRVR, RVR, and cEVR rates when combined with P/R than P/R alone. The addition of
BMS-790052 to P/R was well-tolerated with an AE profile comparable to P/R. These results
support further development of BMS-790052 in combination with P/R or other HCV
antivirals.
Antiviral
Activity
BMS-790052 3
mg QD
+Peg/IFN+RBV
BMS-790052 10
mg QD
+Peg/IFN+RBV
BMS-790052 60
mg QD
+Peg/IFN+RBV
Placebo
+Peg/IFN+RBVN=12
-
8/9/2019 EASL 2010 - Oral Presentations
2/2
N=12 N=12 N=12a
eRVR (Weeks 4and 12
undetectable) N
(%)
5 (41.7%) 10 (83.3%) 9 (75%) 1 (8.3%)
RVR (Week 4
undetectable) N
(%)
5 (41.7%) 11 (91.7%) 10 (83.3%) 1 (8.3%)
cEVR (Week 12
undetectable) N
(%)
7 (58.3%) 10 (83.3%) 10 (83.3%) 5 (41.7%)
Adverse Events
SAEs N (%) 1 (8.3%) 1 (8.3%) 1 (8.3%) 0
AEs leading to
discontinuation
N (%)
1 (8.3%) 0 2 (16.7%) 1 (8.3%)
Grade 3-4 AEs N
(%)1 (8.3%) 1 (8.3%) 2 (16.7%) 3 (25%)
HCV RNA measured by Roche Taqman High Pure v2.0 (LOD