Date: 2015-07-23
Type of information: Submission of an sNDA
Product name: Olysio™ and sofosbuvir
Compound: simeprevir and sofosbuvir
Therapeutic area: Infectious diseases
Action mechanism: direct-acting antiviral agent/protease inhibitor/RNA polymerase (NS5B) inhibitor Simeprevir is an NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir and indicated for the treatment chronic hepatitis C infection in combination with pegylated interferon and ribavirin in HCV genotype 1 and 4 infected patients with compensated liver disease, including cirrhosis. Sofosbuvir is an oral nucleotide analog inhibitor of the HCV NS5B polymerase enzyme, which plays an essential role in HCV replication. This direct-acting agent interferes directly with the HCV life cycle by suppressing viral replication. This nucleotide NS5B polymerase inhibitor is developed by Gilead Sciences.
Company: Janssen (J&J - USA)
Disease: genotype 1 chronic hepatitis C (HCV) in adult treatment-naïve patients with advanced fibrosis and null responders with all stages of liver fibrosis
Latest news: * On July 23, 2015, Janssen Therapeutics announced the submission of a supplemental New Drug Application (sNDA) to the FDA to update the label for once-daily, all-oral Olysio® (simeprevir). Olysio® was approved in November 2014 in combination with sofosbuvir based on the Phase 2 COSMOS clinical trial. This sNDA is based on results from the Phase 3 OPTIMIST-1 and OPTIMIST-2 trials, which evaluated 12 and eight weeks of therapy for treatment-naïve and treatment-experienced genotype 1 CHC adult patients without cirrhosis, and 12 weeks of therapy for treatment-naïve and treatment-experienced genotype 1 CHC adult patients with cirrhosis. OPTIMIST-1 is a Phase 3, randomized, open-label trial to investigate the efficacy and safety of the all-oral regimen of simeprevir and sofosbuvir (SMV/SOF) among treatment-naive and treatment-experienced genotype 1 CHC patients without cirrhosis. The primary study endpoint is sustained virologic response (SVR) at 12 weeks after treatment (SVR12) with 12 and eight weeks of treatment with SMV/SOF versus a historical control (patients previously treated with approved regimens containing a direct-acting antiviral, pegylated interferon and ribavirin). Ninety-seven (97) percent of patients treated with SMV/SOF for 12 weeks (n=150/155) achieved SVR12, which was superior to the SVR12 rate of 87 percent among the historical control. * On November 6, 2014, Medivir announced that the FDA has approved Olysio® (simeprevir) in combination with sofosbuvir as an all-oral, interferon- and ribavirin-free treatment option for genotype 1 chronic hepatitis C infection in adult patients as part of a combination antiviral treatment regimen. The sNDA was filed in May by Medivir’s partner Janssen Research & Development. Data supporting the Olysio® and sofosbuvir combination regimen are from the COSMOS study, an open-label, randomized phase II clinical trial that investigated the efficacy and safety of 12 or 24 weeks of Olysio® (150 mg once daily) in combination with sofosbuvir (400 mg once daily), with or without ribavirin in HCV genotype 1 chronically infected naïve and treatment-experienced adult patients with compensated liver disease.The recommended treatment duration of Olysio® with sofosbuvir is 12 weeks for patients without cirrhosis or 24 weeks for patients with cirrhosis. In the COSMOS study 95 percent of patients (20/21) with METAVIR F0-F3 (patients with no liver fibrosis to near cirrhotic liver disease) receiving 12 weeks of Olysio® with sofosbuvir achieved SVR12 (sustained virologic response 12 weeks after the end of treatment). Regardless of whether patients were treatment-naïve or treatment-experienced 86 percent of patients (6/7) with METAVIR F4 (cirrhosis) receiving 12 weeks of Olysio® in combination with sofosbuvir achieved SVR12, while 100 percent (10/10) of patients with cirrhosis who were treated with the combination for 24 weeks achieved SVR12. For all patients in the COSMOS trial (treatment-naïve and treatment-experienced, METAVIR F0-F4), 93 percent (26/28) achieved SVR12 after 12 weeks and 97 percent (30/31) achieved SVR12 after 24 weeks of treatment. In the COSMOS trial, the most common (> 10 percent) adverse reactions reported during 12 weeks of treatment with Olysio® in combination with sofosbuvir without ribavirin were fatigue (25 percent), headache (21 percent), nausea (21 percent), insomnia (14 percent) and pruritus (11 percent). Rash and photosensitivity were reported in 11 percent and 7 percent of patients, respectively. During 24 weeks of treatment, dizziness (16 percent), and diarrhea (16 percent) were also reported. * On July 15, 2014, Medivir announced that the FDA has assigned a Priority Review designation to the supplemental New Drug Application (sNDA) for the use of once-daily Olysio® (simeprevir) in combination with sofosbuvir for 12 weeks treatment of adult patients with genotype 1 chronic hepatitis C. The sNDA was filed in May by Medivir’s strategic partner Janssen Research & Development LLC. * On May 7, 2014, Medivir has announced that Janssen has submitted a supplemental New Drug Application (sNDA) to the Food and Drug Association (FDA) for simeprevir, an NS3/4A protease inhibitor marketed as Olysio™ in the United States, in combination with the nucleotide analogue NS5B polymerase inhibitor sofosbuvir developed by Gilead Sciences. Olysio™ is currently approved in the U.S. for the treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen. Olysio™ efficacy has been established in combination with peginterferon alfa and ribavirin in HCV genotype 1-infected patients with compensated liver disease, including cirrhosis. This regulatory submission is for the treatment of genotype 1 chronic hepatitis C (HCV) in adult treatment-naïve patients with advanced fibrosis and null responders with all stages of liver fibrosis. The regulatory submission for Olysio™ and sofosbuvir is supported by data from the phase II COSMOS study which included treatment-naïve patients with advanced fibrosis (METAVIR F3 to F4 scores) and prior null-responder patients with all stages of liver fibrosis (METAVIR F0 to F4 scores). Janssen R&D Ireland Ltd initiated in April 2014 the phase III OPTIMIST (Optimal Treatment with a simeprevir and sofosbuvir Therapy) trials examining the safety and efficacy of simeprevir and sofosbuvir without interferon or ribavirin for the treatment of chronic genotype 1 HCV infection. In the first trial, known as OPTIMIST-1, the combination will be administered once daily for 8 or 12 weeks in chronic HCV genotype 1 infected patients without cirrhosis who are HCV treatment naive or treatment experienced. In the second trial, known as OPTIMIST-2, the combination will be administered once daily for 12 weeks in HCV genotype 1 infected patients with cirrhosis who are HCV treatment naive or treatment experienced.
SVR12 rates of 100 percent were seen among patients with IL28B CC genotype (n=43/43) and those with baseline NS5A and NS3 Q80K polymorphisms (n=9/9).
Patients treated with eight weeks of SMV/SOF achieved an SVR12 rate of 83 percent (n=128/155), which was not superior to the SVR12 rate of 83 percent in the historical control.
High SVR12 rates were seen among patients with baseline HCV RNA < 4 million IU/mL (96 percent; n=46/48), IL28B CC genotype (93 percent; n=38/41), patients with genotype 1b CHC (92 percent; n=36/39) and patients without baseline NS5A and Q80K polymorphisms (89 percent; n=78/88).
The most frequently reported adverse events in the 12- and eight-week treatment arms were headache (14 and 17 percent, respectively), fatigue (12 and 15 percent, respectively) and nausea (15 and 9 percent, respectively).
OPTIMIST-2 is a Phase 3, open-label, single-arm trial to investigate the efficacy and safety of SMV/SOF in treatment-naive and treatment-experienced genotype 1 CHC patients with cirrhosis. The primary endpoint is SVR12 with SMV/SOF versus a historical control. Twelve (12) weeks of treatment with SMV/SOF resulted in SVR12 rates of 84 percent (n=86/103), which was superior to the SVR12 rate of 70 percent in the historical control.
Higher SVR12 rates were seen in patients with baseline NS5A polymorphisms with or without NS3 Q80K polymorphisms (100 percent; n=13/13), patients with albumin ≥4 g/dL (94 percent; n=47/50) and treatment-naïve patients (88 percent; n=44/50).
The most common adverse events were fatigue (20 percent), headache (20 percent) and nausea (11 percent).
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2014-11-05
UE authorization:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news:
