Clinical development in hepatitis C, already moving fast, took another couple of lurches yesterday with the victory of Gilead Sciences’ sofosbuvir in two phase III trials and Idenix Pharmaceuticals’ admission of defeat with two of its nucleotides.
Gilead now finds itself closer to having a therapy for all hepatitis C genotypes. More importantly, the coveted prize of the first all-oral regimen to hit market is within its grasp. According to EvaluatePharma’s consensus data, sofosbuvir is forecast to grab nearly half of the $11bn hep C market in 2018.
Fission for compliments
Gilead’s Fission study showed sofosbuvir plus ribavirin to be non-inferior to Roche’s Pegasys plus ribavirin, while the Neutrino trial proved that sofosbuvir plus ribavirin and pegylated interferon alfa-2a bettered a predefined historic control.
Fission and Neutrino are two of the four pivotal trials that will permit filings for sofosbuvir; the Positron trial reported in November and the fourth, Fusion, is set to read out this month or next. Gilead will seek approval for the drug as an all-oral combo with ribavirin for virus genotype 2 and 3, and in combination with ribavirin and the injected Pegasys for genotypes 1, 4, 5 and 6. The filing is expected in summer, with Matthew Roden, an analyst at UBS, saying that the data will support approval in all genotypes. Launch is expected next year.
Analysts from Leerink Swann said that Neutrino data appeared to be the best in the interferon add-on setting, and that the drug’s safety profile was “pristine”. The analysts cautioned that Fission showed a lower response rate for genotype 3 patients, who would likely require either treatment duration of more than 12 weeks with the oral combo or an additional antiviral added to the mix.
With the same active metabolite as Bristol Myers-Squibb’s BMS-986094, dropped in August following reports of a death and kidney toxicity, the writing was already on the wall for IDX184 and the structurally similar IDX19368 (Bristol-Myers setback another blow to hep C field, August 24, 2012).
Idenix must now rely on IDX719, the subject of a non-exclusive deal with J&J. Data from two phase II trials should appear by the end of the year (Idenix sees small silver lining with Johnson & Johnson tie-up, January 29, 2013).
Idenix has some hope that the J&J collaboration will yield an all-oral combination, but by then it will be too late: four companies have interferon-free regimens in phase III at the moment. As well as Gilead chasing genotypes 1-3, Abbott is testing an all-oral combo in genotype 1 patients and Bristol-Myers Squibb and Boehringer Ingelheim are trialling theirs in patients with genotype 1b.
Gilead is the favourite to win the hep C arms race, and with a therapy that can address all genotypes, its nuc could be a weapon of mass destruction.
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