Final data from the Phase 2 COSMOS study of Janssen’s once-daily simeprevir in combination with sofosbuvir presented at The International Liver Congress™ 2014

Janssen R&D Ireland (Janssen) today announced positive new data from the clinical development programme of simeprevir, including final data from cohort 2 of the Phase 2 COSMOS study of the protease inhibitor simeprevir administered once daily with Gilead Sciences Inc.’s nucleotide inhibitor sofosbuvir, with and without ribavirin (RBV), in adult patients chronically infected with genotype 1 hepatitis C virus (HCV). The final data, along with an additional analysis from COSMOS cohort 1 and new subgroup analyses of Phase 3 data in European and genotype 4 HCV patients, were presented at The International Liver Congress™ 2014 of the European Association for the Study of the Liver (EASL) in London.

Final Phase 2 Data from the Interferon-free COSMOS study

Cohort 2¹
Final results from cohort 2 of the Phase 2 COSMOS study* found that overall, 94 percent of genotype 1 treatment-naïve and prior null-responder HCV patients, with advanced liver fibrosis (METAVIR F3 or F4 scores) treated with simeprevir in combination with sofosbuvir, with or without RBV, for either 12 or 24 weeks achieved sustained virologic response 12 weeks after the end of treatment (SVR12). In patients treated with simeprevir and sofosbuvir alone, 93 percent and 100 percent of patients achieved SVR12 after 12 weeks and 24 weeks of treatment, respectively. The addition of RBV did not improve SVR rates; 93 percent of patients treated with the ribavirin-containing regimen achieved SVR12 after both 12 weeks and 24 weeks of treatment. Among HCV genotype 1a patients without Q80K, overall 97 percent of patients achieved SVR12 after 12 or 24 weeks of treatment regardless of treatment regimen, respectively. All patients with HCV genotype 1b achieved SVR12, regardless of treatment regimen or duration.

Among patients with baseline characteristics typically considered more difficult to treat, overall 98 percent of patients with the IL28B CT genotype, 95 percent of patients with the IL28B TT genotype, 95 percent of patients with METAVIR F4 scores, and 96 percent of genotype 1a patients with the Q80K polymorphism at baseline achieved SVR12. The most common adverse events reported during the study were fatigue, headache and nausea.

An analysis of data from cohort 1 of the COSMOS study* demonstrated that overall 97 percent and 96 percent of genotype 1 HCV patients with METAVIR F0-F1 scores and F2 scores, respectively, treated with simeprevir and sofosbuvir alone achieved SVR12 after both 12 and 24 weeks of treatment. In patients treated with the ribavirin-containing regimen, 100 percent achieved SVR12 after 12 weeks and 24 weeks of treatment, respectively.

Among HCV genotype 1a patients with Q80K, 83 percent and 100 percent of patients treated with simeprevir and sofosbuvir alone achieved SVR12 after 12 or 24 weeks of treatment, respectively, compared to 89 percent of patients treated with simeprevir and sofosbuvir in combination with ribavirin. All patients with HCV genotype 1b achieved SVR12, regardless of treatment regimen or duration. Among patients with baseline characteristics typically considered more difficult to treat, overall 100 percent of patients with the IL28B CT genotype, 83 percent of patients with the IL28B TT genotype, and 100 percent of patients with IL28B CC gentoype achieved SVR12. All patients without the Q80K polymorphism achieved SVR12, regardless of treatment regimen or duration. Adverse events (AEs) were mostly Grade 1/2 (77.5%); no serious AEs were reported, two patients discontinued treatment due to AEs.³

“The efficacy seen with the combination of simeprevir and sofosbuvir is very promising, especially considering the inclusion of patients with more advanced liver fibrosis in Cohort 2,” said Dr. Eric Lawitz, M.D., simeprevir clinical trial investigator, CEO at The Texas Liver Institute and Alamo Medical Research and Clinical Professor of Medicine at University of Texas Health Science Center. “I look forward to seeing the combination of simeprevir and sofosbuvir further evaluated in the recently initiated Phase 3 OPTIMIST trial.”

Phase 3 Efficacy Data in European Patients with Genotype 4 Hepatitis C

Results from the Phase 3 RESTORE trial of simeprevir in combination with pegylated interferon and ribavirin in HCV genotype 4 treatment-naïve and treatment-experienced patients demonstrated that overall 65 percent of patients achieved SVR12, including 83 percent of treatment-naïve patients, 86 percent of prior relapsers, 60 percent of prior partial responders, and 40 percent of prior null responders. Among patients with genotype 4a and 4d HCV, 69 percent and 52 percent achieved SVR12, respectively.

In patients with the IL28B CT and TT genotypes, 66 percent and 60 percent achieved SVR12, respectively. Among patients with more severe liver fibrosis characterized by a METAVIR score of F3 or F4, 67 percent and 47 percent achieved SVR12, respectively.The most frequent adverse events included influenza-like illness, asthenia (weakness) and fatigue. Genotype 4 HCV is considered particularly difficult to treat and currently only limited treatment options are available.⁴

Subgroup Analyses of European Patients from Phase 3 Studies of Simeprevir

Analyses of pooled efficacy data from the QUEST-1 and QUEST-2 studies found 87 percent of European patients treated with simeprevir in combination with pegylated interferon (PegIFN) and RBV achieved SVR12, compared to 81 percent in the overall study population.⁵ In an analysis from the PROMISE study, 88 percent of European patients treated with simeprevir in combination with PegIFN and RBV achieved SVR12 compared to 79 percent in the overall study population.⁶

The efficacy of simeprevir in combination with pegylated interferon and ribavirin was also observed among European patients with baseline characteristics typically considered more difficult to treat. In QUEST-1 and QUEST-2, 71 percent of patients with METAVIR F4 scores, 86 percent of patients with the IL28B CT genotype, 69 percent of patients with the IL28B TT genotype and 64 percent of genotype 1a patients with the Q80K polymorphism at baseline achieved SVR12 in the simeprevir arm, compared to 25 percent, 44 percent, 31 percent and 50 percent of patients in the placebo arm, respectively. In PROMISE, 85 percent of patients with METAVIR F4 scores, 88 percent of patients with the IL28B CT genotype, 77 percent of patients with the IL28B TT genotype and 75 percent of genotype 1a patients with the Q80K polymorphism at baseline achieved SVR12 in the simeprevir arm, compared to 30 percent, 41 percent, 18 percent and 57 percent of patients treated in the placebo arm, respectively.^5,6

“The data presented at EASL further reinforce the benefit of simeprevir-based treatment across diverse patient populations, including European patients,” said Gaston Picchio, Hepatitis Disease Area Leader, Janssen Research & Development. “Following the recent positive opinion for simeprevir from the Committee for Medicinal Products for Human Use in the European Union, we look forward to bringing this regimen to patients in Europe in the near future.

References

1. Lawitz M et al. The COSMOS cohort 2 study, abstract presented at the European Associate for the Study of the Liver (EASL) 2014.
2. Sulkowski MS et al. The COSMOS study, oral presentation presented at the European Association for the Study of the Liver (EASL) 2014.
3. Sulkowski MS et al. The COSMOS study, abstract presented at the European Associate for the Study of the Liver (EASL)
4. Moreno C et al. The RESTORE study, abstract presented at the European Association for the Study of the Liver (EASL) 2014.
5. Foster GR et al. The QUEST 1 and 2, abstract presented at the European Association for the Study of the Liver (EASL) 2014.