(Incivek) Approved for Hepatitis C
On May 23 the U.S. FDA approved Vertex's HCV protease inhibitor
telaprevir (brand name Incivek), the second direct-acting
hepatitis C drug launched this month.
(750 mg) is given as two 375-mg tablets three times
daily for 12 weeks.
advent of direct-acting antiviral agents that target different
steps of the hepatitis C virus (HCV) lifecycle will revolutionize
hepatitis C treatment. Current standard therapy -- pegylated interferon
plus ribavirin -- works by stimulating the immune response rather
than directly attacking the virus.
In late April both telaprevir and Merck's
boceprevir were unanimously recommended for approval by the
Food and Drug Administration's Antiviral Drugs Advisory Committee.
was approved for use by adult chronic hepatitis C patients with
HCV genotype 1 and compensated liver disease; the indication includes
both treatment-naive individuals and prior non-responders or relapsers.
It has not yet been approved for HIV positive people, though recently
reported data show that it improves response rates in HIV/HCV
The standard oral dose is 750 mg 3-times-daily with food. Telaprevir
should be taken for the first 12 weeks in combination with pegylated
interferon (Pegasys or PegIntron) plus ribavirin; telaprevir is
then stopped while pegylated interferon/ribavirin are continued.
Most people with good early response to the triple combination
can stop all treatment at week 24, while others continue pegylated
interferon/ribavirin through week 48.
The pivotal ADVANCE, ILLUMINATE, and REALIZE trials showed that
adding telaprevir produced higher sustained virological response
(SVR) rates than standard therapy alone. People who achieve SVR
-- generally considered a cure -- reduce their risk of developing
liver cirrhosis and hepatocellular carcinoma.
For treatment-naive genotype 1 patients, SVR rates approached
80% with telaprevir triple therapy, compared with less than 50%
for initial standard therapy; furthermore, most were able to shorten
treatment from 48 to 24 weeks.
In the REALIZE
trial, the likelihood of SVR for genotype 1 non-responders
ranged from 86% for prior relapsers (versus 22% with a second
course of standard therapy alone) to 32% for prior "null
responders" who experienced no significant reduction in HCV
viral load with previous therapy.
Telaprevir was generally well-tolerated in studies to date, but
about half of patients developed skin rash or itching, including
a small number with severe skin reactions such as Stevens-Johnson
Syndrome. Adding telaprevir to standard therapy also increases
the risk of developing anemia.
"With the approval of Incivek, there are now two important
new treatment options for hepatitis C that offer a greater chance
at a cure for some patients with this serious condition,"
said Edward Cox, MD, MPH, director of the Office of Antimicrobial
Products in FDA's Center for Drug Evaluation and Research. "The
availability of new therapies that significantly increase responses
while potentially decreasing the overall duration of treatment
is a major step forward in the battle against chronic hepatitis
Vertex is expected to begin shipping telaprevir by the end of
the month. The company has put in place a financial assistance
and patient support program to help people with limited resources
gain access to telaprevir.
"Hepatitis C can lead to liver failure, cancer and the need
for a transplant, and for the past decade, the best we could offer
patients was a year of difficult treatment that resulted in a
viral cure for fewer than half of them," said Phase 3 principal
investigator Ira Jacobson, MD, from Weill Cornell Medical College
in a press release issued by Vertex. "With Incivek, 79 percent
of people new to treatment achieved a viral cure."
Vertex's news release, including findings from Phase 3 trials,
important safety information, and patient assistance information,
is available online at http://investors.vrtx.com/releasedetail.cfm?ReleaseID=580154.
Full Incivek Prescribing Information is available at http://www.incivek.com.
Incivek label information is also available from the FDA at http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf.
Food and Drug Administration. FDA Approves Incivek for Hepatitis
C. Press release. May 23, 2011.
R Klein and K Struble (FDA). Approval of Incivek (telaprevir),
a direct acting antiviral drug to treat hepatitis C virus (HCV).
FDA Hepatitis Update. May 23, 2011.
FDA Approves Incivek (telaprevir) for People with Hepatitis C.
Press release. May 23, 2011.