VICTRELIS™ (boceprevir), First-in-Class Oral Hepatitis C Virus Protease Inhibitor, Approved in the European Union for Treatment of Chronic Hepatitis C

2011-08-23

WHITEHOUSE STATION, N.J., July 18, 2011 – Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the European Commission (EC) has approved VICTRELIS™ (boceprevir) for the treatment of chronic hepatitis C (CHC) 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. Chronic hepatitis C virus (HCV) is a potentially serious viral infection of the liver that affects an estimated 4 million people in Europe.

The European Commission's Decision grants a single marketing authorisation that is valid in the 27 countries that are members of the European Union (EU), as well as unified labeling applicable to the European Economic Area members, Iceland, Liechtenstein and Norway.

"The EU approval of VICTRELIS for chronic hepatitis C genotype 1 is very exciting, because we now have a new option for patients with the hardest to treat form of the disease. With VICTRELIS, patients who have failed previous therapy or are new to treatment can significantly improve their chances of clearing the virus from their bodies compared to current standard therapy," said Rafael Esteban, M.D., head of the internal medicine and liver unit of the Hospital Universitario Val d’Hebron, Barcelona, Spain. "For some patients new to treatment, VICTRELIS also may allow for a shorter total duration of therapy."

VICTRELIS is the first in a new class of medicines known as HCV protease inhibitors. It is a Direct Acting Antiviral (DAA) agent designed to interfere with the ability of the hepatitis C virus to replicate by inhibiting a key viral enzyme (NS3/4A serine protease). Current standard therapy for HCV works to strengthen the body’s natural immune response to the virus, but a majority of patients with chronic hepatitis C genotype 1 are not able to achieve a sustained virologic response (SVR). 1

“VICTRELIS is the first major advancement for the treatment of chronic hepatitis C approved in the EU in a decade, and represents an important step forward for people living with this serious disease and the physicians who treat them," said Bruno Strigini, president, Europe/Canada, Merck. “Recognizing the high unmet need in this area, Merck will work closely with local authorities across the EU to make VICTRELIS available to patients as quickly as possible.”

The marketing authorization for VICTRELIS in combination with current standard therapy is based on the efficacy and safety results from two large pivotal Phase III clinical studies conducted at European and North American sites that evaluated approximately 1,500 adult patients with chronic HCV genotype 1 infection who were previously untreated or who had failed prior therapy. Both studies included two treatment arms with VICTRELIS: a response-guided therapy (RGT) arm, in which patients with undetectable virus (HCV-RNA) at treatment week 8 were eligible for a shorter duration of therapy, as well as a 48-week treatment arm. All patients receiving VICTRELIS in these studies were first treated with peginterferon alfa-2b and ribavirin (P/R) in a 4-week lead-in phase, followed by the addition of VICTRELIS after week 4. The studies also included a control arm in which patients received 48 weeks of treatment with P/R alone. Final results of the HCV SPRINT-2 (treatment-naïve) study and the HCV RESPOND-2 (treatment-failure) study were published in the New England Journal of Medicine on March 31, 2011.

VICTRELIS in the United States
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.

VICTRELIS is indicated in the U.S. 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 inluding 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), 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.

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 6 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.

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com.

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VICTRELIS™ is a trademark of Schering Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., USA.

Revatio ® and Adcirca® are trademarks of their respective owners and are not trademarks of Merck & Co., Inc., Whitehouse Station, N.J., USA.

Please see Prescribing Information for VICTRELIS at
http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf
and Medication Guide for VICTRELIS at
http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_mg.pdf.

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.