New data from Phase 3 attain study of Janssen’s once-daily simeprevir compared to telaprevir in treatment-experienced adult patients with genotype 1 chronic hepatitis C

Janssen R&D Ireland (Janssen) today announced the presentation of new data for the protease inhibitor simeprevir at the Conference of the Asian Pacific Association for the Study of the Liver (APASL) in Brisbane, Australia. The data demonstrate the safety and efficacy of simeprevir administered once daily with pegylated interferon (pegINF) and ribavirin (RBV) in the treatment of genotype 1 chronic hepatitis C virus (HCV) treatment-naïve or treatment-experienced adult patients with compensated liver disease, including the Phase 3 ATTAIN study in treatment-experienced patients which used telaprevir plus pegINF and RBV as a comparator arm.

“Hepatitis C is a major problem throughout the Europe, Middle East and Africa regions, where 61 million people are living with the disease,” said Brian Woodfall, Head of Development & Global Medical Affairs, Infectious Diseases/Vaccines. “The data presented at APASL show simeprevir to have good efficacy and is better tolerated than some existing treatments, offering convenient once daily dosing for patients with this devastating disease.”

Results from ATTAIN show simeprevir achieved its primary endpoint of non-inferiority to telaprevir in treatment-experienced HCV patients and demonstrated an improved tolerability profile.¹ The aim of the Phase 3 ATTAIN study (n=763) is to demonstrate the non-inferiority of simeprevir versus telaprevir with pegINF and RBV in difficult to cure HCV genotype 1-infected patients who were null or partial responders to prior pegINF and RBV therapy. The results of the ATTAIN head to head study found that 54 percent of partial- and null-responder patients treated with simeprevir, administered once daily in combination with pegINF and RBV, achieved the primary endpoint of sustained virologic response 12 weeks after the end of treatment (SVR12) compared to 55 percent of patients treated with telaprevir, administered three-times daily plus pegINF and RBV.1 Among prior null-responder patients, 44 percent of patients in the simeprevir arm achieved SVR12 versus 46 percent of patients in the telaprevir arm.

Among prior partial-responder patients, 70 percent of patients in the simeprevir arm achieved SVR12 versus 69 percent of patients in the telaprevir arm. In addition, the study also found that 60 percent of patients with the IL28B CC genotype, 55 percent of CT patients and 48 percent of TT patients in the simeprevir arm achieved SVR12, versus 67, 57 and 50 percent of patients in the telaprevir arm, respectively.¹

The most common adverse events during the first 12 weeks of treatment occurred at a consistently lower frequency in the simeprevir treatment arm compared to the telaprevir treatment arm, including pruritus (31 percent versus 43 percent), fatigue (32 percent versus 38 percent), headache (25 percent versus 29 percent), anemia (13 percent versus 37 percent), and nausea (17 percent versus 28 percent). Only two percent of patients in the simeprevir arm versus eight percent of patients in the telaprevir arm discontinued treatment early due to an adverse event. Serious adverse events were reported in two percent of patients in the simeprevir arm and nine percent of patients in the telaprevir arm,¹ underlining the advantages of simeprevir in terms of safety profile.

Pooled analyses of the QUEST-1, QUEST-2 and PROMISE studies confirm efficacy of simeprevir combination therapy in genotype 1b HCV patients (Abstracts 348 and 241)^2,3
Additional data presented at APASL include the QUEST-1 and QUEST-2, and PROMISE studies. The QUEST-1 and QUEST-2 studies were global Phase 3, randomised, double-blind studies evaluating simeprevir with pegIFN/RBV for the treatment of genotype 1 treatmentnaïve HCV patients. In a pooled analysis of the QUEST-1 and QUEST-2 studies (n=785), 89 percent of treatment-naïve genotype 1b HCV patients treated with simeprevir in combination with pegIFN/RBV and met the criteria for response guided therapy (94 percent) achieved SVR12 compared to 53 percent of patients treated with placebo in combination with pegIFN/RBV. In patients typically considered difficult to treat, 71 percent of patients with the IL28B TT genotype and 78 percent with METAVIR F3-F4 scores achieved SVR12 in the simeprevir arm. Two percent of patients in each treatment arm discontinued treatment with simeprevir or placebo early due to an adverse event.²

An analysis of the Phase 3 PROMISE study (n=393) looking at efficacy in genotype 1b patients found that 89 percent of prior-relapser genotype 1b HCV patients treated with simeprevir in combination with pegylated interferon and ribavirin and met the criteria for response guided therapy (95 percent) achieved SVR12 compared to 43 percent of patients treated with placebo in combination with pegylated interferon and ribavirin. In patients typically considered difficult to treat, 68 percent of patients with the IL28B TT genotype and 84 percent with METAVIR F3-F4 scores achieved SVR12 in the simeprevir arm. No patients discontinued treatment with either simeprevir or placebo due to adverse events during the entire treatment phase in this analysis of PROMISE.³

References

1. Reddy KR et al. The ATTAIN study, abstract presented at the Conference of the Asian Pacific Association for the Study of the Liver (APASL).
2. Dore GJ et al. The QUEST 1 and 2, abstract presented at the Conference of the Asian Pacific Association for the Study of the Liver (APASL).
3. Gane EJ et al. The PROMISE study, abstract presented at the Conference of the Asian Pacific Association for the Study of the Liver (APASL).