Enanta Pharmaceuticals, Inc., has announced that Abbott initiated an interferon-free combination phase III clinical trial for hepatitis C (HCV) that included the collaboration’s protease inhibitor, ABT-450. This trial was initiated following the release of positive results from the study known as "Aviator", a phase IIb trial designed and conducted by Abbott. The initiation of this phase III trial, part of Abbott’s global registration programme, triggered a collaboration milestone payment to Enanta.
The focus of ABT-450 development is to study the compound in combination with other antiviral agents in Abbott’s HCV portfolio. The three direct acting antivirals, or triple DAA cocktail, studied in the Phase 2b interferon-free Aviator trial included ritonavir-boosted protease inhibitor ABT-450/r, non-nucleoside polymerase inhibitor ABT-333, and NS5A inhibitor ABT-267.
Initial results from the Aviator trial show sustained virological response at 12 weeks post-treatment (SVR12) in 99 per cent of treatment-naïve (n=77), and 93 per cent of null-responders (n=41), genotype 1 (GT1) HCV patients taking a combination of ABT-450 with ritonavir (ABT-450/r), ABT-267, ABT-333 and ribavirin for 12 weeks, based on an observed data analysis.
“The high SVR12 rates achieved in the genotype 1-infected population and the tough-to-treat IL28B non-CC genotype patient populations are very encouraging,” commented Jay Luly, president and CEO of Enanta. “We look forward to the phase III development of this interferon-free, oral treatment regimen containing our collaboration’s HCV protease inhibitor, ABT-450.”
The study results will be presented at the 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), from November 9-13, 2012, in Boston.
The observed data analysis used in this abstract does not include six patients who had not yet reached post-treatment week 12 or had missing values (data points) at the time of the abstract submission. All virologic failures and safety discontinuations were included in the analysis.
The objective of this phase II b study was to assess the safety and efficacy of ABT-450/r (dosed 100/100 to 200/100mg QD), ABT-267 (25mg QD), ABT-333 (400mg BID) and ribavirin in non-cirrhotic treatment-naïve patients and prior peg-interferon/ribavirin null responders for 8, 12, or 24 weeks.
Enrollment was open to GT1-infected patients regardless of IL28B host genotype, and ribavirin dosing was weight-based.
Additional data presented in the abstract represent all 8- and 12-week arms (n=448) of this 14-arm study (571 patients enrolled: 438 treatment-naïve and 133 prior null responders). SVR12 rates for other 8- and 12-week regimens ranged from 89-92 per cent. Complete SVR12 data for 8- and 12-week arms will be presented at the AASLD Meeting.
Four of 448 patients (one percent) in the 8- and 12-week arms discontinued due to adverse events. Of five serious adverse events (1 percent), 1 (arthralgia or joint pain) was possibly study drug-related. In the trial, the most common adverse events were fatigue (28 and 27 per cent) and headache (28 and 31 per cent) for treatment naïve and null responders, respectively.
Enanta Pharmaceuticals is a research and development-focused biotechnology company that uses its robust chemistry-driven approach and drug discovery capabilities to create small molecule drugs in the infectious disease field.
In December 2006, Enanta and Abbott announced a worldwide agreement to collaborate on the discovery, development and commercialization of HCV NS3 and NS3/4A protease inhibitors and HCV protease inhibitor-containing drug combinations. Under the agreement, Abbott is responsible for all development and commercialization activities for ABT-450, the program’s lead compound. Enanta received a $57 million upfront payment upon signing the collaboration agreement and is eligible to receive additional pre-commercial milestones, as well as, double-digit royalties on any revenue allocable to the collaboration’s protease inhibitors. Also, for any additional collaborative HCV protease inhibitor product candidate developed under the agreement, Enanta holds an option to fund 40 percent of US development costs and US commercialization efforts (sales and promotion costs) in exchange for 40 per cent of any US profits ultimately achieved after regulatory approval.
Enanta Pharmaceuticals is a research and development-focused biotechnology company that uses its robust chemistry-driven approach and drug discovery capabilities to create small molecule drugs in the infectious disease field.