Prix Galien Canada Innovative Drug Product 2012
ex aequo Incivek (telaprevir)
The Prix Galien Canada 2012- Innovative Product has been awarded ex aequo to Incivek (telaprevir) marketed by Vertex Pharmaceuticals Canada Ltd. Telaprevir is a new protease inhibitor (PI) that inhibits HCV replication in vitro and in vivo. It is one of the two first direct acting antivirals (DAA) available in Canada for the treatment of chronic G1 genotype hepatitis C infection in combination with pegylated interferon (IFN) and ribavirin (R) in patients who are treatment naive, those who failed prior treatment and those with compensated liver disease including cirrhosis.
Approval was based on Phase III studies in treatment naive and previously treated patients. The ADVANCE trial in naive patients resulted in a sustained virologic response (SVR) rates of 69% and 75% in the 8-week and 12-week administration arms respectively compared to 44% in the control arm. The REALIZE trial in previously treated patients had three arms : tela-previr plus IFN-R for 12 weeks followed by IFN-R for 36 weeks, an arm with a 4-week lead-in period of IFN-R prior to combination with telaprevir and a con- trol arm of IFN-R for 48 weeks. SVR rates in the two telaprevir arms were similar with 64 and 66% suggest- ing that the lead-in period conferred no benefit. The SVR rate in the control arm was 17%. Telaprevir inhibits cytochrome CYP3A and therefore should not be used with drugs such as rifampin, statins and midazolam that are metabolized by this enzyme.
The most common adverse effects are rash, fatigue, prutitis, anemia, nausea, other GI symptoms, and dys- geusia. In the clinical trials, rash developed in 56% of the patients receiving the drug compared to 34% in the control arms. The rash was severe in 4% of the treated patients compared to <1% in the control patients. The drug should be stopped if severe rash develops. Addition of telaprevir to IFN-R results in increased drop in haemoglobin but discontinuation was low at 4%. In summary, telaprevir is one of the first two direct acting antivirals available in Canada for the treatment of chronic genotype1 hepatitis C infection. The prote-ase inhibitors have been shown to be very effective in a number of studies and appear to have shortened the duration of treatment for the chronic genotype 1 hepatitis C infection. It represents a significant improvement in the treatment of the disease.
Ms. Louise Proulx, vice-president of Vertex accepts the Prix Galien Canada 2012 - Innovative Product Award from Dr. Jacques Gagné, Prix Galien Canada Jury President.
Prix Galien Canada 2012 Innovative Drug Productex aequo Victrelis (boceprivir)
The Prix Galien Canada 2012- Innovative Drug Product has been awarded ex aequo to Victrelis (boceprivir) marketed by Merck Canada Inc. Boceprivir is the first computer-designed NS3 protease inhibitor (PI) available in Canada for the treatment of G1 genotype hepatitis C infection in combination with pegylated interferon alpha 2-b (IFN) and ribavirin (R) therapy in adults with compensated liver disease.
Boceprivir is a covalently reversible HCV NS3/4A serine protease inhibitor, an enzyme that cleaves HCV encoded polyproteins of the genotype 1 virus. It is metabolized in the liver and excreted in the feces with a half-life of 3.4 hours. The treatment regimen used in the pivotal approval tri- als consisted of a 4-week lead-in course of IFN-R therapy followed by either Results Guided Therapy (RGT) in which boceprivir was administered for 24 weeks but dis-continued after 28 weeks for patients with undetectable viral RNA at week 8 through 24, or fixed dose treatment in which boceprovir was administered continuously for 44 weeks. All arms continued to receive IFN-R for the entire duration of treatment and IFN-R was continued to complete 48 weeks of treatment in the RGT arm. When compared to IFN-R alone (plus placebo), the elimination of the virus was achieved in almost 70% of treatment naive patients compared to 40% in patients who received IFN-R plus placebo and 60% of treatment- experienced patients compared to 21% for IFN-R plus placebo. Canadian patients were included in the clinical trials and authorship of the major studies included phy- sicians at the University of British Columbia. It is impor- tant to note that black patients, more difficult to treat than white patients, were included in the studies and that their response was better with the triple therapy than with IFN-R but was only about half of the response noted in white patients.
Boceprivir being partly metabolized by cytochrome CYP3A4 and a strong inhibitor of that enzyme is prone to drug interactions. Therefore drugs that induced or inhibit CYP3A4 could have a significant effect on the therapeutic effect. The most common adverse effects of boceprivir are fatigue, nausea, headache, dysgeusia and anemia. In fact 50% of the patients under the triple therapy developed anemia compared to 25% of the patients under IFN-R treatment. Anemia was successfully treated with eryth- ropoietin (EPO) or by dose reduction of ribavirin. In summary, boceprivir is one of the first two direct acting antivirals, a new class of compounds, for the treatment of chronic genotype 1 hepatitis C. The protease inhibitors have been shown to be very effective and appear to have shortened the duration of the treatment for chronic genotype 1 hepatitis C infection. It represents a significant advance in the treatment of the disease.
Mr. Gregg Szabo, Vice president, Merck Canada Inc. accepts the Prix Galien Canada 2012 - Innovative Product Award from Dr. Jacques Gagné, Prix Galien Canada Jury President.