Replies to post #73395 on Biotech Values

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AASLD ABT-333 abstract:

Treatment-naïve, HCV genotype 1-infected subjects show significantly greater HCV RNA decreases when treated with 28 days of ABT-333 plus peginterferon and ribavirin compared to peginterferon and ribavirin alone

M. Rodriguez-Torres1; E. Lawitz2; D. Cohen3; L. M. Larsen3; R. Menon3; C. Collins3; T. Marsh3; S. Gibbs3; B. Bernstein3
1. Fundación de Investigación de Diego, San Juan, PR, USA.
2. Alamo Medical Research, San Antonio, TX, USA.
3. Abbott Laboratories, Abbott Park, IL, USA.


Objective: ABT-333 is a potent nonnucleoside HCV polymerase inhibitor with a favorable safety profile in healthy subjects. This study assesses the safety, antiviral activity, and pharmacokinetics (PK) of ABT-333 with peginterferon alfa-2a (pegIFN) and ribavirin (RBV) in HCV-infected subjects.
Methods: 30 HCV genotype 1-infected, treatment-naïve subjects were randomized to ABT-333 300 mg BID (N=8), 600 mg BID (N=8), 1200 mg QD (N=8), or placebo (n=6) for 28 days (2 days monotherapy plus 26 days with pegIFN 180 mcg/wk + RBV 1000-1200 mg/d, weight-based). Safety was monitored by adverse events (AEs) and lab results. ABT-333 PK profile was assessed on Day 1; samples were also collected Days 2, 4, 5, 10, 17, 24 and 28.
Results: Subjects were primarily male (70%) and white (90%); 43% were of Latino ethnicity. At baseline, the mean (SD) age was 46.5 (9.8) yrs and the mean weight was 78.6 (13.2) kg. Treatment with ABT-333+pegIFN/RBV resulted in statistically significantly greater decreases in HCV RNA versus placebo+pegIFN/RBV (Figure). The least square mean maximum HCV RNA change from baseline was -3.7, -4.0, and -3.5 log10 IU/mL for 300 mg BID, 600 mg BID, and 1200 mg QD ABT-333+pegIFN/RBV, respectively, compared to -1.4 log10 IU/mL for placebo+pegIFN/RBV. Mean ABT-333 Cmax and AUC increased with increasing doses and were comparable to healthy subjects. Based on mean trough values, addition of pegIFN/RBV did not alter ABT-333 PK. AEs were generally mild and attributed to pegIFN or RBV. Of ABT-333-associated AEs, nausea, headache, flatulence, and dermatitis were most common (N=2-3 for each AE). There were no serious AEs or discontinuations due to AEs. Lab abnormalities were similar in subjects receiving ABT-333 and placebo.
Conclusion: ABT-333 was well tolerated for 28 days when dosed with pegIFN/RBV and resulted in significant decreases in HCV RNA versus pegIFN/RBV alone.