Notice of Decision for ^PrINCIVEK™

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Contact: Bureau of Gastroenterology, Infection and Viral Diseases (BGIVD)

Date issued: September 22, 2011

On August 16, 2011, Health Canada issued a Notice of Compliance to Vertex Pharmaceuticals (Canada) Incorporated for the drug product Incivek.

Incivek contains the medicinal ingredient telaprevir, which is an antiviral agent. Incivek is a specific hepatitis C virus protease inhibitor.

Incivek, in combination with peginterferon (Peg-IFN) alfa and ribavirin (RBV), is indicated for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease, including cirrhosis, who are treatment naïve or who have previously been treated with interferon-based treatment, including prior null responders, partial responders, and relapsers.

The market authorization was based on quality, non-clinical, and clinical information submitted. The efficacy and safety of Incivek were primarily based on the analyses of Phase 2 and 3 studies conducted with Incivek in combination with Peg-IFN-alfa/RBV in either treatment-naïve patients or previously treated patients (null responders, partial responders, relapsers). The sustained virologic response (SVR: 24 weeks after the last planned dose) was evaluated for all patients who received at least one dose of the treatment within each study. Results from these studies, especially Phase 3 studies, showed that Incivek, when used for 12 weeks in combination with either 24 or 48 weeks of treatment with Peg-IFN-alfa/RBV, produced sustained virologic response rates that were superior compared to 48 weeks of treatment with Peg-IFN-alfa/RBV alone. In addition, this result was irrespective of whether patients were treatment-naïve, or patients who were previously treated with Peg-IFN-alfa/RBV, including prior null responders, partial responders, and relapsers.

Incivek (375 mg, telaprevir) is supplied in a tablet form. The recommended dose of Incivek is 750 mg (two 375-mg tablets) taken orally three times a day (7-9 hours apart) with food. The total daily dose is six tablets (2,250 mg). Consultation of the Incivek Product Monograph prior to initiation of therapy is highly recommended for further dosing guidelines. Incivek must not be administered as a single drug therapy, but only in combination with Peg-IFN-alfa/RBV. The Product Monographs of Peg-IFN-alfa/RBV must be consulted prior to initiation of therapy with Incivek.

Incivek, in combination with Peg-IFN-alfa/RBV is contraindicated for:

• patients who are hypersensitive to telaprevir or to any ingredient in the formulation or component of the container;
• women who are pregnant or men whose female partners are pregnant;
• when combined with drugs that are highly dependent on cytochrome P450 (CYP) 3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (narrow therapeutic index). Incivek is also contraindicated when combined with drugs that strongly induce CYP3A and thus may lead to lower exposure and loss of efficacy of Incivek.

The contraindications to Peg-FN-alfa/RBV also apply to Incivek combination treatment. Refer also to the prescribing information for Peg-IFN-alfa/RBV.

Incivek should be administered under the conditions stated in the Product Monograph taking into consideration the potential risks associated with the administration of this drug product. Detailed conditions for the use of Incivek are described in the Product Monograph.

Priority Review Status was granted for the evaluation of Incivek as it appeared to provide substantial evidence of increased clinical efficacy such that the overall benefit/risk profile is improved over existing therapies.

Based on the Health Canada review of data on quality, safety, and efficacy, Health Canada considers that the benefit/risk profile of Incivek is favourable for the indication stated above.

Notices of Decision (NDs) are produced in accordance with the Summary Basis of Decision (SBD) initiative. All NDs will be reproduced within the corresponding SBD, normally available within 5 months of product authorization.