Merck and Roche expand agreement in fight against chronic hepatitis C

Merck (NYSE: MRK), known as MSD outside the United States and Canada, announced today that it has signed a new non-exclusive agreement with Roche (SIX: RO, ROG; OTCQX: RHHBY), through the companies’ respective subsidiaries, for the global promotion, upon appropriate marketing approvals, of VICTRELIS™ (boceprevir) as part of a triple combination therapy regimen with peginterferon alfa and ribavirin (peg/riba).

“Reaching physicians with important information about the use of VICTRELIS in combination with peg/riba is essential as we enter this new era in the field of chronic hepatitis C,” said Adam H. Schechter, executive vice president and president, Global Human Health, Merck. “We’re pleased to work with Roche to help physicians help patients with chronic hepatitis C around the world.”

Under the terms of the agreement, Roche and Merck will work together in global markets, including Europe, Asia and Latin America, to educate physicians and patients about hepatitis C virus (HCV). The companies previously announced an agreement to promote VICTRELIS in the United States and collaborate to explore new treatment regimens for patients with chronic HCV.

“Improving treatment outcomes for more patients with chronic hepatitis C is our ultimate goal,” said Pascal Soriot, Roche Pharmaceuticals Division, chief operating officer. “Through this extended collaboration and the education of health care professionals, Roche and Merck aim to ensure that appropriate patients can benefit from triple combination therapy.”

VICTRELIS in the United States

In the United States, VICTRELIS is approved for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult patients (18 years of age and older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy. The following points should be considered when initiating VICTRELIS for treatment of chronic hepatitis C infection:

• VICTRELIS must not be used as monotherapy and should only be used in combination with peginterferon alfa and ribavirin.
• VICTRELIS efficacy has not been studied in patients who have previously failed therapy with a treatment regimen that includes VICTRELIS or other HCV NS3/4A protease inhibitors.
• VICTRELIS in combination with peginterferon alfa and ribavirin has not been studied in patients documented to be historical null responders (less than a 2 log HCV-RNA decline by treatment week 12) during prior therapy with peginterferon alfa and ribavirin. The clinical studies included patients who were poorly interferon responsive. Patients with less than 0.5 log HCV-RNA decline in viral load at treatment week 4 with peginterferon alfa plus ribavirin alone are predicted to have a null response (less than a 2 log HCV-RNA decline by treatment week 12) to peginterferon alfa and ribavirin therapy.

Poorly interferon responsive patients who were treated with VICTRELIS in combination with peginterferon alfa and ribavirin have a lower likelihood of achieving a sustained virologic response (SVR)1, and a higher rate of detection of resistance-associated substitutions upon treatment failure, compared to patients with a greater response to peginterferon alfa and ribavirin.

VICTRELIS was approved by the U.S. Food and Drug Administration on May 13 and is available to all U.S. pharmacies nationwide, including specialty pharmacies.

On July 18, Merck announced that the European Commission (EC) approved VICTRELIS for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult patients with compensated liver disease who are previously untreated or who have failed previous therapy.

Important U.S. safety information about VICTRELIS

All contraindications to peginterferon alfa and ribavirin also apply since VICTRELIS must be administered with peginterferon alfa and ribavirin. Because ribavirin may cause birth defects and fetal death, VICTRELIS in combination with peginterferon alfa and ribavirin is contraindicated in pregnant women and in men whose female partners are pregnant. Avoid pregnancy in female patients and female partners of male patients. Patients must have a negative pregnancy test prior to therapy; have monthly pregnancy tests; and use two or more forms of effective contraception, including intrauterine devices and barrier methods, during treatment and for at least six months after treatment has concluded. Systemic hormonal contraceptives may not be as effective in women while taking VICTRELIS. VICTRELIS is contraindicated in coadministration with drugs that are highly dependent on CYP3A4/5 for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events. VICTRELIS also is contraindicated in coadministration with potent CYP3A4/5 inducers where significantly reduced boceprevir plasma concentrations may be associated with reduced efficacy. Drugs that are contraindicated with VICTRELIS include: alfuzosin, carbamazepine, phenobarbital, phenytoin, rifampin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, St. John’s Wort (hypericum perforatum), lovastatin, simvastatin, drosperinone, Revatio® (sildenafil) or Adcirca® (tadalafil) (when used for the treatment of pulmonary arterial hypertension), pimozide, triazolam, and midazolam (orally administered).

Anemia has been reported with peginterferon alfa and ribavirin therapy. The addition of VICTRELIS to peginterferon alfa and ribavirin is associated with an additional decrease in hemoglobin concentrations. The addition of VICTRELIS may result in a worsening of neutropenia associated with peginterferon alfa and ribavirin alone. Complete blood counts should be obtained pretreatment, and at treatment weeks 4, 8 and 12, and should be monitored closely at other time points, as clinically appropriate. If a patient has a serious adverse reaction potentially related to peginterferon alfa and ribavirin therapy, the peginterferon alfa and/or ribavirin dose should be reduced or discontinued. VICTRELIS must not be administered in the absence of peginterferon alfa and ribavirin.

The most commonly reported adverse reactions (greater than 35 percent) in clinical trials in adult patients receiving the combination of VICTRELIS with peginterferon alfa-2b and ribavirin were fatigue, anemia, nausea, headache and dysgeusia. Of these commonly reported adverse reactions, fatigue, anemia, nausea, and dysgeusia occurred at rates greater than or equal to 5 percent above the rates for peginterferon alfa and ribavirin alone in either clinical study. The incidence of these adverse reactions in previously untreated patients who received VICTRELIS combination therapy compared with peginterferon and ribavirin alone were: fatigue (58 vs. 59 percent), anemia (50 vs. 30 percent), nausea (46 vs. 42 percent), dysgeusia (35 vs. 16 percent), respectively. The incidence of these adverse reactions in previously treated patients who received VICTRELIS combination therapy compared with peginterferon and ribavirin alone were: fatigue (55 vs. 50 percent), anemia (45 vs. 20 percent), nausea (43 vs. 38 percent), dysgeusia (44 vs. 11 percent), respectively.

VICTRELIS is a strong inhibitor of CYP3A4/5 and is partly metabolized by CYP3A4/5. The potential for drug-drug interactions must be considered prior to and during therapy.

Please see U.S. prescribing information at: http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf.

Merck’s global commitment to advancing hepatitis therapy

Merck is committed to building on its strong legacy in the field of viral hepatitis by continuing to discover, develop and deliver vaccines and medicines to help prevent and treat viral hepatitis. In hepatitis C, company researchers developed the first approved therapy for chronic HCV in 1991 and the first combination therapy in 1998. In addition to ongoing studies with VICTRELIS, extensive research efforts are underway to develop additional innovative oral therapies for viral hepatitis treatment.

Reference

1. SVR, the protocol specified primary efficacy endpoint of the pivotal studies, is defined as achievement of undetectable HCV-RNA at 24 weeks after the end of treatment in all randomized patients treated with any study medication. Per protocol, if a patient did not have a 24-week post-treatment assessment, the patient’s 12-week post-treatment assessment was utilized.