J&J HCV drug OK'd; educational push planned
Janssen's hepatitis C drug Olysio (simeprevir) scored FDA approval Friday evening, kicking off a new wave of hepatitis C drugs. It offers modest benefit over standard of care, but a subgroup of patients has encountered resistance, and the med could have trouble catching on as newer antivirals become more broadly available for treating the liver-destroying disease.
An NS3/4A protease inhibitor, Olysio was approved as part of a treatment regimen that also includes pegylated interferon (INF) and ribavirin (RBV) in patients with genotype-1 infection, which accounts for most cases of the virus. It followed a unanimous vote from an FDA ad-com panel in October for that same genotype.
Janssen has priced Olysio at a wholesale acquisition price of $22,120 per bottle of 28 capsules (150 mg capsules), which is an approximately one-month supply. "We believe that the price of Olysio reflects its value and demonstrated efficacy and safety profile," said Janssen spokesman Craig Stoltz via e-mail, adding that Janssen is offering a support program including help with access.
That's roughly $66,360 for a three-month course. Pooled analysis of two Phase III trials demonstrated that 80% of treatment-naïve patients taking Olysio were able to clear the virus at 12 weeks (SVR12), vs. 50% of patients in placebo groups.
Efficacy wise, the drug offers a slight benefit over the two currently used direct-acting antivirals, Vertex's Incivek and Merck's Victrelis (both of which were approved in 2011), with similar to better safety/tolerability, according to an October analyst note from inThought Research.
But the efficacy of Olysio, in combination with INF and RBV, is greatly decreased in patients who have genotype 1a Q80K, a naturally occurring variation in the HCV NS3/4A protease enzyme that was identified in 48% of patients with GT-1a infection. In the two Phase-III studies involving treatment-naïve patients, among those with GT-1a receiving Olysio who had the Q80K polymorphism, 58% achieved SVR12 vs. 84% of patients without the Q80K polymorphism. In the placebo arm, 52% of patients with the Q80K polymorphism achieved SVR12. Prior-relapser patients also showed a reduced effect.
"Regarding Q80K, Janssen has long been committed to patient education and plans to make information about resistance testing available to providers," added Stoltz. "This includes details regarding the availability of NS3 sequencing testing and referring them to the diagnostic companies for specific questions about the tests that are offered."
The issue could, nevertheless, impact the new drug's market share. Gilead's much-anticipated NS5B inhibitor sofosbuvir, now awaiting approval with a PDUFA date of December 8, 2013, is also expected to launch with a regimen that contains INF and RBV for GT-2 and GT-3 patients.
Gilead is expected to rack up more than 50% of the HCV market and at least $2.3 billion in global annual sales by 2016, according to an inThought forecast, possibly more depending on the extent of the treatable population. Olysio could still pick up $637 million in global annual sales in that timeframe, the analysts predict.
Of note, Gilead has studied an INF- and RBV-free combo of sofosbuvir + simeprevir in the COSMOS study, which included treatment naïve or previous null responder patients. The oral cocktail demonstrated SVR4 rates of 96% and 100% with or without RBV, respectively, as reported by inThought. Gilead, however, is likely to promote sofosbuvir with its own ledipasvir (GS-5885), an NS5A protein inhibitor, rather than with Olysio.
For J&J's part, in October it acquired an NS5A oral compound from GlaxoSmithKline called GSK805, which it will look to commercialize in its own all-oral regimen. “This combination would include a protease inhibitor, a non-nucleoside polymerase inhibitor, and an NS5a inhibitor, which is the same combination AbbVie is using in its ‘Aviator' combination of ABT-450/r + ABT-267 + ABT-333 with or without ribavirin,” wrote inThought. “These oral combinations, however, are missing a nucleoside NS5b inhibitor like Gilead's sofosbuvir.”
J&J will probably be late to the all-oral game behind Gilead and AbbVie, whose INF-free regimen is in Phase III. Second-wave companies also include Bristol-Myers Squibb and Merck.