Committee Unanimously Recommends Telaprevir (Incivek)
The FDA Antiviral Drugs Advisory Committee last week voted
18-0 to recommend approval of the HCV protease inhibitor telaprevir
(Incivek) for people with genotype 1 chronic hepatitis C.
advent of direct-acting antiviral agents that target different
steps of the hepatitis C virus (HCV) lifecycle is expected to
revolutionize hepatitis C treatment. While these drugs will initially
be used in combination with the current standard of care -- pegylated
interferon plus ribavirin -- all-oral combinations are currently
first drugs out of the pipeline are 2 HCV protease inhibitors,
(now given the brand name Incivek) and Merck's boceprevir
(Victrelis). On April 28 the Antiviral Drugs Advisory Committee
of the U.S. Food and Drug Administration (FDA) unanimously voted
to recommend approval of telaprevir. The committee also gave a
nod to boceprevir the previous day.
committee reviewed clinical trial data (including findings from
the Phase 3 ADVANCE, ILLUMINATE, and REALIZE studies) showing
that combining telaprevir with pegylated interferon/ribavirin
produced a higher cure rate -- and in less time -- than standard
therapy alone. This improvement is most notable for hard-to-treat
patients including those with HCV genotype 1, people with liver
cirrhosis, and those who did not respond to a prior course
of interferon-based therapy.
most extensively studied regimen added 750 mg 3-times-daily telaprevir
to pegylated interferon/ribavirin for 12 weeks, followed by pegylated
interferon/ribavirin alone through 24 or 48 weeks, using a response-guided
strategy based on early response. Telaprevir boosted sustained
virological response rates to around 70% overall (and 80% for
treatment-naive individuals), compared with less than 50% for
standard therapy alone.
is generally well-tolerated, but it increases the risk of skin
rash and anemia; a small number of people in trials to date have
developed severe skin reactions including Stevens-Johnson syndrome.
In most cases, however, rash is mild-to-moderate and resolves
after telaprevir is discontinued.
committee recommended further studies looking at people of African
descent -- a population that responds more poorly to interferon
-- but commended Vertex for already conducting a study of telaprevir
in people with HIV/HCV coinfection (reported at this year's
Retrovirus conference in February).
pending approval of telaprevir and boceprevir bring up a host
of issues, including how best to use these drugs to avoid development
of resistance, the importance of adherence, and whether HCV protease
inhibitors should now be considered the comparison standard of
care when conducting clinical trials of new agents.
full FDA is not required to accept committee recommendations,
but it usually does so. Agency approval of telaprevir and boceprevir
is expected by the end of May, and if that occurs, the drugs will
likely be commercially available by the end of the summer.
"Hepatitis C is a curable disease with potentially devastating
consequences if left untreated, so we are pleased by the committee's
unanimous recommendation to approve telaprevir for a broad group
of people with hepatitis C," Peter Mueller, PhD, Chief Scientific
Officer and Executive Vice President of Global Research and Development
at Vertex, said in a company press release. "We look forward
to working with the FDA as it prepares to make its decision next
Briefing materials on telaprevir provided by the FDA and Vertex
are available online at [http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/
Pharmaceuticals. FDA Advisory Committee Unanimously Recommends
Approval of Telaprevir for People with Hepatitis C. Press release.
April 28, 2011.
Walker. FDA Panel Endorses Another HCV Drug. MedPage Today.
April 28, 2011.