EASL-Danoprevir:Roche reports high rates of sustained viral clearance

Roche reports high rates of sustained viral clearance with investigational hepatitis C treatment danoprevir

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced data showing high SVR12 rates (maintaining undetectable viral levels 12 weeks after stopping treatment) and good tolerability with its second generation protease inhibitor danoprevir in IFN-containing regimens for hepatitis C (HCV). In the DAUPHINE study up to 93% of genotype 1 and 100% of genotype 4 patients achieved SVR12 with ritonavir-boosted danoprevir, IFN and ribavirin, considered a clinical cure¹.

“The high sustained viral response rates and encouraging safety data show danoprevir is potent and well-tolerated.” said Hal Barron, M.D., Head of Global Product Development and Chief Medical Officer for Roche. “Roche’s HCV portfolio includes multiple investigational drugs with different modes of action, allowing us to develop tailored treatments that aim to address the future needs of patients with chronic hepatitis C.”

In a second study, INFORM-SVR, 71% of genotype 1b patients achieved SVR12 with boosted danoprevir, the nucleoside analogue polymerase inhibitor mericitabine and ribavirin as part of an IFN-free regimen².

DAUPHINE and INFORM-SVR will be presented at the 47th Annual Meeting of the European Association for the Study of the Liver (EASL) congress in Barcelona.

The prevalence of different HCV genotypes across the world, as well as increasing numbers of patients with harder-to-treat disease, co-morbidities or cirrhosis means that patients may have varying needs for future treatment combinations.

Boosted danoprevir is a potent protease inhibitor (DAUPHINE study)

Preliminary data from the 421 patient DAUPHINE study showed SVR12 rates of 93%, 83% and 67% following 24 weeks of treatment with 200, 100 or 50mg of boosted danoprevir respectively in genotype 1 and 100% in genotype 4 patients with boosted danoprevir, Pegasys (peginterferon alfa-2a) and ribavirin.

Patients randomised to a fourth arm testing response-guided therapy (RGT) with 12 weeks of danoprevir 100mg achieved an overall SVR12 rate of 74%. Further analysis showed SVR12 rates of up to 90% in patients with genotype 1a HCV, the most difficult-to-treat viral subtype, and up to 97% in patients with genotype 1b HCV. Danoprevir was well-tolerated at all doses evaluated.

Interferon-free regimen (INFORM-SVR study)

Data from the 169 patient INFORM-SVR study showed that 71% of genotype 1b HCV patients achieved SVR12 with a 24 week IFN-free regimen of ritonavir-boosted danoprevir, mericitabine and ribavirin. The combination was well-tolerated with no neutropenia, treatment emergent liver toxicity or new safety signals observed.

The new data from INFORM-SVR shows that mericitabine enhances the barrier to resistance, enabling an IFN-free regimen in combination with boosted danoprevir and ribavirin. Viral suppression on treatment was high and viral breakthrough while on treatment was low, although this benefit was not maintained off treatment in the majority of genotype 1a patients, resulting in an SVR12 of 26%.

About DAUPHINE

DAUPHINE is a Phase IIb study in treatment-naive, non-cirrhotic adults with HCV genotype 1/4 infection randomised to receive 24 weeks of treatment with danoprevir boosted with ritonavir at the following doses 200/100, 100/100 or 50/100mg bid, in combination with Pegasys and ribavirin (Arms A, B and C, respectively). Patients assigned to the response-guided therapy Arm D received boosted danoprevir 100/100 mg bid with Pegasys and ribavirin for 12 weeks and stopped all treatment if they achieved extended rapid viral response (eRVR) (HCV RNA <15 IU/mL through weeks 2–10) or continued to week 24 if they did not achieve eRVR. The control group received Pegasys and ribavirin for 48 weeks (Arm E).

About INFORM-SVR

INFORM-SVR is a randomised phase IIb study exploring mericitabine plus ritonavir-boosted danoprevir with or without ribavirin in treatment-naive, noncirrhotic, HCV genotype 1-infected patients. Patients received a combination of mericitabine (1000 mg bid) and boosted danoprevir (100 mg/100 mg bid) plus ribavirin (1000/1200 mg daily) for 24 weeks.

About danoprevir

Danoprevir is Roche’s investigational protease inhibitor that is active against HCV genotypes 1, 4 and 6. Protease inhibitors are expected to become a core component of highly effective future HCV treatments. To date, danoprevir with ritonavir-boosting has shown highly promising efficacy with a good safety profile in clinical testing.

About mericitabine

Mericitabine is Roche’s investigational nucleoside analogue polymerase inhibitor (nPol) for HCV. In previous clinical trials in patients with chronic hepatitis C, mericitabine has been studied alone as monotherapy, in combination with peginterferon alfa-2a (40KD) plus ribavirin, and in combination with the HCV protease inhibitor danoprevir in a dual all-oral interferon-free regimen. The patient population that has received the drug in phase I and II clinical trials encompasses individuals infected with HCV genotypes 1, 2, 3 and 4, and both treatment-naive and treatment-experienced patients.

About Roche in Hepatitis

Roche has a longstanding history of innovative and groundbreaking research, and development of new medicines and diagnostic tools, for people living with viral hepatitis. Since 2001, Pegasys (peginterferon alfa-2a) has been used by nearly 1.5 million patients worldwide and is a foundation of the current standard of care of treatment for patients with chronic hepatitis C and B. Development efforts are underway with several novel molecules including danoprevir, mericitabine and setrobuvir that have potential to advance treatment options for hepatitis. Roche is also at the forefront in HCV testing and monitoring. The company's commitment to health care practitioners and patients is supported by its best-in-class access and support services.

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalized healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2011, Roche had over 80,000 employees worldwide and invested over 8 billion Swiss francs in R&D. The Group posted sales of 42.5 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com .

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References

1) Everson, G et al. Rapid and sustained achievement of undetectable HCV RNA during treatment with ritonavir-boosted danoprevir/Peg-IFNα-2A/RBV in HCV genotype 1 or 4 patients: DAUPHINE week 12 interim analysis. Poster presentation at EASL 2012.
2) Gane, EJ et al. Interferon-free treatment with a combination of mericitabine and danoprevir/r with or without ribavirin in treatment-naïve HCV genotype-1 infected patients. Poster presentation at EASL 2012.