Vertex Pharmaceuticals Incorporated announced that the Antiviral Drugs Advisory Committee to the US Food and Drug Administration (FDA) voted unanimously to recommend FDA approval of telaprevir for people with genotype 1 chronic hepatitis C.
The Committee recommended by a vote of 18-0 the approval of telaprevir for those who were not treated previously and those who were treated previously but not cured with currently available medicines.
Telaprevir was studied in all major subgroups of people who were treated previously and not cured: relapsers, partial responders and null responders. The FDA is expected to make a decision on the approval of telaprevir by May 23, 2011, under the Prescription Drug User Fee Act (PDUFA). The FDA is not bound by the Committee's recommendation, but usually follows its advice.
In phase III studies, telaprevir was given for 12 weeks in combination with pegylated-interferon and ribavirin (P/R) followed by P/R alone for a total of 24 weeks or 48 weeks of treatment. Data from these studies that were reviewed by the Committee showed that people who received telaprevir-based combination therapy achieved significantly higher rates of Sustained Viral Response (SVR, or viral cure) compared to treatment with 48 weeks of P/R alone, regardless of their experience with prior treatment. Among people who were not treated previously, 79 percent achieved a viral cure with telaprevir-based combination therapy compared to 46 percent who achieved a viral cure with P/R alone.
Approximately two-thirds of people in phase III studies who were not treated previously and who received telaprevir-based combination therapy were eligible to complete their treatment in six months — half the time needed with currently available medicines. Today, the FDA Committee discussed Vertex's request for the approval of response-guided therapy to allow for a six-month treatment duration for people who were not treated previously as well as for those who relapsed after prior treatment with P/R alone (prior relapsers).
Side effects observed with telaprevir-based combination therapy were consistent across the phase III studies. Rash and anaemia occurred more frequently among those treated with telaprevir-based combination therapy compared with those who received pegylated-interferon and ribavirin alone.
“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,” said Peter Mueller, Ph.D., chief scientific officer and executive vice president of Global Research and Development at Vertex. “We look forward to working with the FDA as it prepares to make its decision next month.”
The safety profile of telaprevir has been well characterized. Data from more than 40 clinical studies across a broad group of nearly 4,000 people were included in the new drug application. The side effects observed with telaprevir-based combination therapy were consistent across the Phase 3 studies. The most common side effects, regardless of treatment arm, were fatigue, pruritus (itchiness), nausea, headache, rash, anaemia, flu-like symptoms, insomnia and diarrhoea with the majority being mild to moderate.
Rash and anaemia occurred more frequently among those treated with telaprevir-based combination therapy. In phase III studies, discontinuation of all medicines due to either rash or anaemia during the telaprevir/placebo treatment phase was approximately 1 percent for rash and 1 percent for anaemia. Rash was primarily characterized as eczema-like, manageable and resolved following discontinuation of telaprevir. More than 90 percent of rash was mild to moderate and investigators in the studies primarily used topical corticosteroids and/or antihistamines to treat rash. Anaemia was primarily managed by reducing the dose of ribavirin.
Telaprevir is an investigational, oral inhibitor that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. More than 2,800 people with hepatitis C have received telaprevir-based combination therapy as part of phase II and phase III studies. The phase III registration studies, Advance, Illuminate and Realize, evaluated telaprevir (750 mg, taken three times daily) in combination with Pegasys (pegylated-interferon alfa-2a) and Copegus (ribavirin) in people with hepatitis C who had not been treated before as well as those who were treated before but not cured with a prior treatment course of P/R.
Vertex is developing telaprevir in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America.
Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver. Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer. Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.
Unlike HIV and hepatitis B virus, chronic hepatitis C is curable. However, approximately 60 percent of people who undergo treatment with an initial 48-week regimen of pegylated-interferon and ribavirin, the currently approved medicines for genotype 1 hepatitis C, do not achieve SVR or viral cure. If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.