When EMA adopted its current guideline in 2008, hepatitis C patients were still reliant on treatment regimens that featured interferon. That changed with the 2013 approval of Sovaldi, which offered the majority of hepatitis C patients a comparatively quick, safe way to treat their infections. With Sovaldi, its follow-up Harvoni (ledipasvir/sofosbuvir) and rival products from AbbVie and Merck having completely changed the face of hepatitis C care in Europe, EMA has decided that the guideline it wrote in the previous era of treatment is no longer fit for purpose.
In response, EMA has released a new, 19-page guideline for consultation. The guideline calls for trials designed to show viral clearance to use sustained virological response as the primary endpoint. EMA wants sponsors to measure hepatitis C RNA 12 weeks after the end of therapy, and conduct follow-up tests to confirm the durability of the response to a novel drug regimen. With Sovaldi and its rivals having reset expectations in hepatitis C care, new treatments will need to generate impressive safety and efficacy data.
The effectiveness of existing drugs is reflected in EMA’s expectation that clinical trials will feature an active comparator arm. EMA is open to dropping this requirement in some circumstances. If a drug delivers very high sustained virological response rates in Phase II, EMA may free sponsors of the obligation to run a randomized controlled study. In this situation, a safety trial comparing the drug to an active comparator or placebo, plus an uncontrolled efficacy study, could be sufficient. The flexibility is a reflection of the negligible rate of spontaneous resolutions in hepatitis C.
EMA is accepting comments on the draft guideline until 31 December.
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