May 22, 2011

Eighty Percent of Surveyed Pharmacy Directors Report that Higher Rebates and Discounts Prompted Their Managed Care Organization to Offer Preferential Reimbursement, According to a New Report from HealthLeaders-InterStudy and Fingertip Formulary

NASHVILLE, Tenn. & GLEN ROCK, N.J.--(EON: Enhanced Online News)--HealthLeaders-InterStudy and Fingertip Formulary find that superior clinical attributes of hepatitis C therapies, such as convenience, improved compliance and improved tolerability, have little influence over reimbursement status compared to rebates and discounts. According to the recent Formulary Forum report entitled Formulary Advantages in Hepatitis C: Despite the Near Certainty of Emerging Oral Protease Inhibitors, Pharmacy Directors Remain Unsure of the Value and Reimbursement Status of Triple Therapy Protocols, most (80 percent) surveyed pharmacy directors report that higher rebates and discounts lead to preferential reimbursement from U.S. health plans.  

The report finds that a greater percentage of managed care organizations receive rebates and discounts for Roche’s Pegasys (peginterferon alpha-2a) than for Merck’s PegIntron (peginterferon alpha-2b). In April 2011, the U.S. Food and Drug Administration recommended the approval of Merck’s boceprevir and Vertex Pharmaceuticals’ telaprevir for use in hepatitis C triple therapy regimens. If Roche continues to maintain Pegasys’ preferred reimbursement status, particularly as a means to encourage greater use of triple therapy protocols that include Pegasys, then telaprevir will be more successful than boceprevir.

“The higher success rates for emerging triple therapy regiments compared with conventional dual therapy regimens will result in higher treatment rates for hepatitis C,” said Leigh Compton, M.D., Ph.D., author of the report. “If Merck wants boceprevir to be considered for preferential reimbursement, they need to increase their efforts to improve the reimbursement status of PegIntron among U.S. health plans by offering more generous rebates and discounts, at least until efficacy data for boceprevir in combination with Pegasys are available.”

The new Formulary Forum report is based on a survey of 50 U.S. pharmacy directors who control formularies at national, regional and state-level managed care organizations, as well as historical formulary data from Fingertip Formulary.

About Fingertip Formulary

Fingertip Formulary (www.FingertipFormulary.com), the leading provider of access to and insight into formulary data in the United States, offers comprehensive formulary data covering commercial, Medicaid, Medicare and PBM plans, among others. Fingertip Formulary is a Decision Resources, Inc. company.

About HealthLeaders-InterStudy

HealthLeaders-InterStudy, a Decision Resources, Inc. company, is the authoritative source for managed care data, analysis and news. For more information, please visit www.HL-ISY.com.

About Decision Resources, Inc.

Decision Resources, Inc. is a cohesive portfolio of companies that offers best-in-class, high-value information and insights on important sectors of the healthcare industry. Clients rely on this analysis and data to make informed decisions. Both HealthLeaders-InterStudy and Fingertip Formulary are Decision Resources, Inc. companies. Please visit Decision Resources, Inc. at www.DecisionResourcesInc.com.

All company, brand or product names contained in this document may be trademarks or registered trademarks of their respective holders.
Contacts

Decision Resources, Inc.
Elizabeth Marshall, 781-993-2563
emarshall@dresources.com

Rivals Merck, Roche team up on hepatitis C drugs

The Associated Press May 17, 2011, 4:09PM ET

By LINDA A. JOHNSON

After a decade as rivals, drugmakers Merck & Co. and Roche are teaming up to market their hepatitis C medicines just as drugs from a new class are about to transform treatment of the tough-to-cure virus.

Merck's Victrelis, approved last Friday, and Incivek from Vertex Pharmaceuticals, expected to be approved soon, are the first new treatments for hepatitis C in about 20 years. They significantly boost cure rates when used in combination with the current mainstay drugs, which cause flu-like side effects for months and still don't cure most patients.

Merck, looking to maximize the benefit of being first to market, said Tuesday it's reached a deal under which Roche Holding AG sales representatives will promote Merck's Victrelis pills as part of a new triple combination therapy, with Roche's injected hepatitis C drug Pegasys and ribavirin pills.

"We're maximizing the potential of our new drug" with this deal, Merck spokesman Ian McConnell said in an interview.

Merck salespeople will promote Victrelis along with its similar injected drug, PEG-Intron, and ribavirin. Ribavirin is available as a cheap generic as well as Merck's brand-name drug, Rebetol, and Roche's brand, Copegus.

"Triple combination therapy for hepatitis C marks a major change in the way this disease is treated," Pascal Soriot, chief operating officer of Roche's pharmaceuticals division, said in a statement.

The Roche sales force will start promoting the three-drug combination, likely to cost tens of thousands of dollars for months of treatment, to U.S. physicians, then expand to other countries. The two companies also will educate patients about hepatitis C diagnosis and treatment options.

"This is a win for Roche to safeguard Pegasys' market share," Citigroup Global Markets Inc. analyst John Boris wrote to investors. It's "also a win for Merck to boost promotion of Victrelis."

Meanwhile, researchers at Merck, which is based in Whitehouse Station, N.J., and Switzerland's Roche will collaborate on testing new combinations of existing and experimental hepatitis C medicines from their companies.

The partnership comes after Roche and Merck's Schering-Plough unit spent more than a decade battling for supremacy in the market for hepatitis C drugs. Roche and Schering each produced ribavirin pills and long-acting, genetically engineered versions of the immune system protein interferon: Roche's Pegasys and Schering-Plough's PEG-Intron.

Those injected drugs, together with ribavirin, boost the immune system to fight the hepatitis C virus.

Victrelis and Incivek are part of a new drug class called hepatitis C virus protease inhibitors that block an enzyme needed for the virus to copy itself.

Studies showed the Victrelis three-drug regimen boosted the cure rate to about 66 percent after 48 weeks, from about 40 percent with just ribavirin and interferon.

Hepatitis C can linger silently in the body for years or even decades. By the time it's discovered, liver damage is often so severe a transplant is the only option, and livers are always in short supply.

The new combination treatment carries the same serious side effects as the interferon-ribavirin combination, including nausea, anemia, fatigue and a persistent unpleasant taste in the mouth. With the addition of Victrelis, more patients experienced anemia and unpleasant taste. Because ribavirin can damage or kill a fetus, the new combination cannot be taken by pregnant women or their male partners.

Source

Pill Burden a Key Concern With New Chronic Hepatitis C Drugs

Only Kadmon Pharmaceuticals' RIBASPHERE® RIBAPAK® Offers a Reduction in Ribavirin Pill Burden Designed to Increase Treatment Adherence
NEW YORK, NY--(Marketwire - May 18, 2011) - This past Friday, the U.S. Food and Drug Administration (FDA) approved the first of a new generation of chronic hepatitis C drugs, known as protease inhibitors. The drug, VICTRELIS® (boceprevir), from Merck & Co., has been shown to increase the rate of sustained viral response and shorten treatment times when used in combination with the current standard of care, ribavirin and pegylated alpha interferon, in the treatment of chronic hepatitis C. Vertex Pharmaceuticals is seeking approval to market a similar drug, INCIVEK® (telaprevir).

The addition of protease inhibitors to the current standard of care puts a new and significantly greater treatment burden on the patient. Under most treatment regimens, pegylated alpha-interferon is injected once a week, and ribavirin is taken twice a day, for a total of five or six pills when prescribed in generic form. VICTRELIS is taken three times a day, for a total of 12 pills. INCIVEK is also taken three times a day, for a total of 6 pills. A treatment cycle lasting 48 weeks could mean that the patient is responsible for taking over 5,700 pills on schedule for the entire regimen. If the patient does not adhere to the prescribed regimen, the risk of treatment failure or relapse is increased (Reddy KR, Shiffman ML, Morgan TR, et al. Clin Gastroenterol Hepatol. 2007;5:124-129). Furthermore, because of the direct antiviral mechanism of protease inhibitors, missed doses of a protease inhibitor could lead to viral resistance (Weiss, et al. Aliment Pharmacol Ther 2009; 30:14-27).

Kadmon Pharmaceuticals' proprietary RIBASPHERE® RIBAPAK® (ribavirin, USP) is the only ribavirin available in a daily, two-pill compliance package designed to enhance therapy adherence. With RIBASPHERE RIBAPAK, the patient takes only two pills each day -- one in the morning and one at night -- reducing the total ribavirin pill burden by up to 66 percent over a 48 week course of treatment. RIBASPHERE RIBAPAK packaging is clearly marked for seven days of AM and PM dosing, and the completion of a compliance pack reminds the patient to administer their accompanying weekly interferon therapy. Kadmon is also offering patients a daily therapy diary to help keep track of their treatment schedule.

"Maintaining treatment adherence under the burden of a triple therapy combination will require significantly greater vigilance from the patient," said Bruce R. Bacon, M.D., professor of internal medicine at the Saint Louis University School of Medicine, and a clinical investigator for VICTRELIS. "With only one chance at success with this therapeutic approach, RIBASPHERE RIBAPAK represents an invaluable insurance policy for a treatment combination which could transform the enormous public health risks of hepatitis C."

About Hepatitis C

Hepatitis C is a liver disease that results from infection with the hepatitis C virus. It can range in severity from a mild illness lasting a few weeks to a serious, lifelong illness. Hepatitis C virus can be either "acute" or "chronic." Acute hepatitis C virus infection is a short-term illness that occurs within the first 6 months after someone is exposed to the hepatitis C virus. Seventy-five - 85% of acute HCV infections become chronic HCV infections. Chronic hepatitis C virus is a serious disease than can result in long-term health problems, such as serious liver disease, including cirrhosis and liver cancer, or even death. An estimated 3.2 million Americans have a chronic infection of the hepatitis C virus.

About RIBASPHERE® RIBAPAK® (ribavirin, USP)

INDICATION

RIBASPHERE® (ribavirin, USP) in combination with peginterferon alfa-2a is indicated for the treatment of adults with chronic hepatitis C virus infection who have compensated liver disease and have not been previously treated with interferon alpha.

IMPORTANT SAFETY INFORMATION

RIBASPHERE (ribavirin, USP) monotherapy is not effective for the treatment of chronic hepatitis C virus infection and should not be used alone for this indication (see WARNINGS). The primary clinical toxicity of ribavirin is hemolytic anemia. The anemia associated with ribavirin therapy may result in worsening of cardiac disease that has led to fatal and nonfatal myocardial infarctions. Patients with a history of significant or unstable cardiac disease should not be treated with ribavirin. Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin. In addition, ribavirin has a multiple dose half-life of 12 days, and it may persist in non-plasma compartments for as long as 6 months. Ribavirin therapy is contraindicated in women who are pregnant and in the male partners of women who are pregnant. Extreme care must be taken to avoid pregnancy during therapy and for 6 months after completion of therapy in both female patients and in female partners of male patients who are taking ribavirin therapy. At least two reliable forms of effective contraception must be utilized during treatment and during the 6 month post treatment follow-up period.

CONTRAINDICATIONS

RIBASPHERE (ribavirin, USP) is contraindicated in:
  • Patients with known hypersensitivity to RIBASPHERE (ribavirin, USP) or to any component of the tablet.
  • Women who are pregnant.
  • Men whose female partners are pregnant, plan to become pregnant, or are not using contraception.
  • Patients with hemoglobinopathies (e.g., thalassemia major or sickle-cell anemia).
  • In combination with didanosine. Reports of fatal hepatic failure, as well as peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis have been reported in clinical trials.
RIBASPHERE (ribavirin, USP) and peginterferon alfa-2a combination therapy is contraindicated in patients with:
  • Autoimmune hepatitis.
  • Hepatic decompensation (Child-Pugh score greater than 6; class B and C) in cirrhotic CHC monoinfected patients before or during treatment.
  • Hepatic decompensation with Child-Pugh score greater than or equal to 6 in cirrhotic CHC patients coinfected with HIV before or during treatment.
WARNINGS AND PRECAUTIONS

Treatment with RIBASPHERE (ribavirin, USP) and peginterferon alfa-2a should be administered under the guidance of a qualified physician and may lead to moderate to severe adverse experiences requiring dose reduction, temporary dose cessation or discontinuation of therapy.

RIBASPHERE (ribavirin, USP) must not be used alone because ribavirin monotherapy is not effective for the treatment of chronic hepatitis C virus infection.

RIBASPHERE (ribavirin, USP) and peginterferon alfa-2a should be discontinued in patients who develop evidence of hepatic decompensation during treatment.

There are significant adverse events caused by ribavirin/peginterferon alfa-2a therapy, including severe depression and suicidal ideation, hemolytic anemia, suppression of bone marrow function, autoimmune and infectious disorders, ophthalmologic disorders, cerebrovascular disorders, pulmonary dysfunction, colitis, pancreatitis, and diabetes. The peginterferon alfa-2a package insert and medication guide should be reviewed in their entirety prior to initiation of combination treatment for additional safety information.

Pregnancy: Ribavirin may cause birth defects and/or death of the exposed fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients.

Anemia: The primary toxicity of ribavirin is hemolytic anemia (hemoglobin < 10 g/dL), which was observed in approximately 13% of all ribavirin and peginterferon alfa-2a treated patients in clinical trials.

Hepatic Failure: Chronic hepatitis C (CHC) patients with cirrhosis may be at risk of hepatic decompensation and death when treated with alpha interferons, including peginterferon alfa-2a. Cirrhotic CHC patients coinfected with HIV receiving highly active antiretroviral therapy (HAART) and interferon alfa-2a with or without ribavirin appear to be at increased risk for the development of hepatic decompensation compared to patients not receiving HAART.

Hypersensitivity: Severe acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, and anaphylaxis) have been observed during alpha interferon and ribavirin therapy.

Renal Impairment: RIBASPHERE (ribavirin, USP) should not be used in patients with creatinine clearance < 50 mL/min.

Pulmonary: Pulmonary symptoms, including dyspnea, pulmonary infiltrates, pneumonitis, pulmonary hypertension, pneumonia, and occasional cases of fatal pneumonia, have been reported during therapy with ribavirin and interferon. In addition, sarcoidosis or the exacerbation of sarcoidosis has been reported.

Bone Marrow Suppression: Pancytopenia (marked decreases in RBCs, neutrophils and platelets) and bone marrow suppression have been reported in the literature to occur within 3 to 7 weeks after the concomitant administration of pegylated interferon/ribavirin and azathioprine.

Pancreatitis: RIBASPHERE (ribavirin, USP) and peginterferon alfa-2a therapy should be suspended in patients with signs and symptoms of pancreatitis, and discontinued in patients with confirmed pancreatitis.

Laboratory Tests: Before beginning peginterferon alfa-2a/RIBASPHERE (ribavirin, USP) combination therapy, standard hematological and biochemical laboratory tests are recommended for all patients.

Drug Interactions: Nucleoside Analogues: NRTIs: In clinical trials, cases of hepatic decompensation (some fatal) were observed among the CHC/HIV coinfected cirrhotic patients receiving NRTIs. Patients receiving peginterferon alfa-2a/ribavirin and NRTIs should be closely monitored for treatment associated toxicities.

ADVERSE REACTIONS

Peginterferon alfa-2a in combination with ribavirin causes a broad variety of serious adverse reactions. The most common serious or life-threatening adverse reactions induced or aggravated by peginterferon alfa-2a and ribavirin include depression, suicide, relapse of drug abuse/overdose, and bacterial infections, each occurring at a frequency of < 1%. Hepatic decompensation occurred in 2% of CHC/HIV patients. Nearly all patients in clinical trials experienced one or more adverse events.

For more information please see the accompanying RIBASPHERE RIBAPAK (ribavirin, USP) Tablets Full Prescribing Information. The peginterferon alfa-2a Package Insert should be reviewed in its entirety for additional safety information prior to initiation of combination treatment.

About Kadmon Pharmaceuticals
Kadmon Pharmaceuticals LLC is a privately held, New York City-based biopharmaceutical company founded on its expertise in novel science. The company explores new understandings in molecular biology to develop therapies that target the metabolomic or signaling pathways associated with disease, including novel anti hepatitis C therapies. Collaborating with academic centers and private enterprise at the forefront of innovation, Kadmon is focused on pioneering medicines in the areas of oncology, infectious diseases and immunology. For more information, visit www.kadmon.com.

Source 

May 15, 2011

FDA approves Victrelis (Boceprevir) for Hepatitis C

FDA NEWS RELEASE

For Immediate Release: May 13, 2011
Media Inquiries: Erica Jefferson, 301-796-4988, erica.jefferson@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA

FDA approves Victrelis for Hepatitis C

The U.S. Food and Drug Administration today approved Victrelis (boceprevir) to treat certain adults with chronic hepatitis C. Victrelis is used for patients who still have some liver function, and who either have not been previously treated with drug therapy for their hepatitis C or who have failed such treatment. Victrelis is approved for use in combination with peginterferon alfa and ribavirin.

The safety and effectiveness of Victrelis was evaluated in two phase 3 clinical trials with 1,500 adult patients. In both trials, two-thirds of patients receiving Victrelis in combination with pegylated interferon and ribavirin experienced a significantly increased sustained virologic response (i.e., the hepatitis C virus was no longer detected in the blood 24 weeks after stopping treatment), compared to pegylated interferon and ribavirin alone, the current standard of care.

When a person sustains a virologic response after completing treatment, this suggests that HCV infection has been cured.

Sustained virologic response can result in decreased cirrhosis and complications of liver disease, decreased rates of liver cancer (hepatocelluar carcinoma), and decreased mortality.

“Victrelis is an important new advance for patients with hepatitis C,” said Edward Cox, M.D., M.P.H, director, Office of Antimicrobial Products in FDA’s Center for Drug Evaluation and Research. “This new medication provides an effective treatment for a serious disease, and offers a greater chance of cure for some patients’ hepatitis C infection compared to currently available therapy.”

According to the U.S. Centers for Disease Control and Prevention, about 3.2 million people in the United States have chronic hepatitis C, a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure.

Most people with hepatitis have no symptoms of the disease until liver damage occurs, which may take several years.

Most liver transplants performed in the United States are due to progressive liver disease caused by hepatitis C virus infection. After the initial infection with hepatitis C virus (HCV), most people develop chronic hepatitis C. Some will develop cirrhosis of the liver over many years. Cirrhosis can lead to liver damage with complications such as bleeding, jaundice (yellowish eyes or skin), fluid accumulation in abdomen, infections, or liver cancer.

People can get the hepatitis C virus in a number of ways, including: exposure to blood that is infected with the virus; being born to a mother with HCV; sharing a needle; having sex with an infected person; sharing personal items such as a razor, toothbrush with someone who is infected with the virus, or from unsterilized tattoo or piercing tools.

Victrelis is a pill taken three times a day with food. The therapy is part of a class of drugs referred to as protease inhibitors, which work by binding to the virus and preventing it from multiplying.

The most commonly reported side effects in patients receiving Victrelis in combination with pegylated interferon and ribavirin include fatigue, low red blood cell count (anemia), nausea, headache and taste distortion (dysgeusia).

Victrelis is marketed by Whitehouse Station, N.J.-based Merck.

For more information:
FDA: Approved Drugs: Questions and Answers
FDA: What’s New at FDA in Hepatitis
FDA: Hepatitis C Tests
CDC: Hepatitis C Information for the Public

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Source

May 13, 2011

WHITEHOUSE STATION, N.J., May 13, 2011 – Merck (NYSE:MRK) (known as MSD outside the United States and Canada) announced today that the U.S. Food and Drug Administration (FDA) has approved VICTRELIS (boceprevir), the company's innovative new medicine for the treatment of chronic hepatitis C (CHC). VICTRELIS is approved for the treatment of CHC 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 is the first in a new class of medicines approved to treat chronic hepatitis C
VICTRELIS is the first in a new class of medicines known as hepatitis C virus (HCV) protease inhibitors approved for use in combination with peginterferon alfa and ribavirin, which is the current standard therapy, for the treatment of chronic hepatitis C.

“This is an exciting day for physicians and patients because VICTRELIS is the first major advancement for the treatment of chronic hepatitis C approved in a decade,” said Bruce Bacon, M.D., professor of internal medicine, Saint Louis University School of Medicine, and a clinical investigator for VICTRELIS. “Compared to current standard therapy, VICTRELIS can significantly increase a patient’s chance of achieving undetectable levels of the virus, thereby obtaining an SVR. For many patients, VICTRELIS may allow for a shorter total duration of treatment.”

“Merck is deeply committed to innovation in bringing forward new medicines that significantly address unmet medical needs, and VICTRELIS is a shining example of our commitment being realized," said Kenneth C. Frazier, president and chief executive officer, Merck. "We look forward to building on our legacy in the fight against infectious diseases, and to being a part of this exciting new era in the treatment of chronic hepatitis C."

Merck will begin shipping VICTRELIS to pharmacies within a week so that patients will have access to this new medication as soon as possible. In addition, the company is expanding its support of public awareness and education programs for chronic hepatitis C. Resources include coupons to help eligible patients with their medication cost, reimbursement support to help patients understand their insurance coverage for VICTRELIS, and 24/7 nurse phone support.

Separately, Merck will also add VICTRELIS to its patient assistance program through which eligible patients may be able to receive product free of charge.

Current standard therapy for HCV works to strengthen the body’s natural immune response to the virus, but only about 40 percent of patients with chronic HCV genotype 1 infection are able to achieve SVR. VICTRELIS is a Direct Acting Antiviral (DAA) agent that interferes with the ability of the hepatitis C virus to replicate by inhibiting a key viral enzyme (NS3/4A serine protease).

The FDA approval of VICTRELIS is based on the efficacy and safety results from two large Phase III clinical studies that evaluated approximately 1,500 adult patients with chronic HCV genotype 1 infection. 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. Historical null responders were not enrolled.

Adding VICTRELIS to P/R achieved a significant increase in SVR rates compared to P/R alone

Primary results from the two pivotal studies:
  • Treatment-failure patients: the addition of VICTRELIS to P/R resulted in nearly a three-fold increase in SVR rates to 59 percent (96/162) for the RGT arm and 66 percent (106/161) for the 48-week treatment arm, compared to 23 percent (18/80) for control. Relapse rates were 14 percent (16/111) for the RGT arm and 12 percent (14/121) for the 48-week treatment arm, compared to 28 percent (7/25) for control.
  • Treatment-naïve patients: the addition of VICTRELIS to P/R resulted in a significant increase (1.7 fold) in SVR rates to 63 percent (232/368) for the RGT arm and 66 percent (242/366) for the 48-week treatment arm, compared to 38 percent (138/363) for control. Relapse rates were 9 percent (24/257) for the RGT arm and 9 percent (24/265) for the 48-week treatment arm, compared to 22 percent (39/176) for control.
In a separate, pre-specified cohort of 159 Black treatment-naïve patients, the addition of VICTRELIS to P/R resulted in a significant increase in SVR to 42 percent (22/52) for the RGT arm and 53 percent (29/55) for the 48-week treatment arm, compared to 23 percent (12/52) for control. Relapse rates were 12 percent (3/25) for the RGT arm and 17 percent (6/35) for the 48-week treatment arm, compared to 14 percent (2/14) for control.

Many patients receiving VICTRELIS in combination therapy were early responders at treatment week 8

Secondary analyses from the two pivotal studies were as follows:
  • Treatment-failure patients: 46 percent (74/162) of patients in the RGT arm and 52 percent (84/161) of patients in the 48-week treatment arm receiving VICTRELIS had undetectable virus (HCV-RNA) at treatment week 8 and were considered early responders, compared to 9 percent (7/80) for control. The SVR rate for these early responders was 88 percent (65/74) in the RGT arm and 88 percent (74/84) in the 48-week treatment arm, compared to 100 percent (7/7) for control. Early responders in the RGT arm were eligible to stop all treatment at week 36.
  • Treatment-naïve patients: 57 percent (208/368) of patients in the RGT arm and 56 percent (204/366) of patients in the 48-week treatment arm receiving VICTRELIS had undetectable virus (HCV-RNA) at treatment week 8 and were considered early responders, compared to 17 percent (60/363) for control. The SVR rate for these early responders was 88 percent (184/208) in the RGT arm and 90 percent (184/204) in the 48-week treatment arm, compared to 85 percent (51/60) for control. Early responders in the RGT arm were eligible to stop all treatment at week 28.
SVR achieved with VICTRELIS in combination therapy in late responders
  • Treatment-failure patients: Patients who had detectable virus (HCV-RNA) at treatment week 8, but undetectable virus (HCV-RNA) at treatment week 12, and completed at least 36 weeks of treatment, were considered late responders. The SVR rate for these late responders was 79 percent (27/34) in the RGT arm and 72 percent (29/40) in the 48-week treatment arm. Late responders in the RGT arm stopped VICTRELIS at week 36 and continued P/R alone for an additional 12 weeks (48 weeks total).
  • Treatment-naïve patients: Patients who had detectable virus (HCV-RNA) at treatment week 8, but undetectable virus (HCV-RNA) at treatment week 24, and completed at least 28 weeks of treatment, were considered late responders. The SVR rate for these late responders was 66 percent (45/68) in the RGT arm and 75 percent (55/73) in the 48-week treatment arm. Late responders in the RGT arm stopped VICTRELIS at week 28 and continued P/R alone for an additional 20 weeks (48 weeks total).
VICTRELIS in combination therapy increased SVR rates in specific patient populations
  • The addition of VICTRELIS to P/R in treatment-failure patients with less than a 1 log decline in virus (HCV-RNA) during the 4-week lead-in resulted in an increase in SVR rates to 33 percent (15/46) for the RGT arm and 34 percent (15/44) for the 48-week treatment arm, compared to 0 percent (0/12) for control.
  • In treatment-failure patients with cirrhosis at baseline, 77 percent (17/22) achieved SVR with the addition of 44 weeks of VICTRELIS to P/R, compared to 35 percent (6/17) for those who received RGT.
  • In treatment-naïve patients with cirrhosis at baseline, 42 percent (10/24) achieved SVR with the addition of 44 weeks of VICTRELIS to P/R, compared to 31 percent (5/16) for those who received RGT.
Safety and tolerability profile of VICTRELIS in 2,095 patients in Phase II and III studies
  • Serious adverse events were reported in 11 percent of patients receiving VICTRELIS in combination with P/R, compared to 8 percent of patients receiving P/R alone.
  • During the entire course of treatment, the proportion of patients who discontinued treatment due to adverse reactions was 13 percent for patients receiving VICTRELIS in combination with P/R, compared to 12 percent for patients receiving P/R alone. Events resulting in discontinuation were similar to those seen in previous studies with P/R alone.
  • Adverse reactions that led to dose modifications of any drug (primarily P/R) occurred in 39 percent of patients receiving the combination of VICTRELIS with P/R compared to 24 percent of patients receiving P/R alone.
  • The most common reason for dose reduction was anemia, which occurred more frequently in patients receiving the combination of VICTRELIS with P/R than in patients receiving P/R alone.
  • The proportion of patients who experienced anemia was higher in patients receiving VICTRELIS in combination with P/R than in those treated with P/R alone. With management of anemia, the average additional decrease of hemoglobin was approximately 1 g/dL. Dose modifications (generally of P/R) due to anemia occurred more often in patients treated with VICTRELIS in combination with P/R (26 percent), compared to those treated with P/R alone (13 percent). Treatment discontinuations due to anemia were similar for patients receiving VICTRELIS in combination with P/R (1 percent) compared to those treated with P/R alone (1 percent). Erythropoietin (EPO) with or without ribavirin dose reduction for management of anemia was allowed at the discretion of the investigator per the study protocol.
In pivotal clinical studies, the 4-week lead-in provided important clinical insights
Interferon-responsiveness (equal to or greater than a 1 log decline in virus (HCV-RNA) at treatment week 4) was predictive of SVR. Patients receiving VICTRELIS who demonstrated interferon-responsiveness at treatment week 4 achieved higher SVR rates than those with poor interferon-responsiveness (less than a 1 log decline in virus (HCV-RNA) at treatment week 4). During the four-week lead-in period with P/R in the treatment arms containing VICTRELIS, 2 percent (28/1263) of patients experienced adverse reactions leading to discontinuation of treatment.

Background on the pivotal Phase III studies for VICTRELIS
The HCV RESPOND-2 study (treatment-failure patients) and the HCV SPRINT-2 study (treatment-naïve patients) each evaluated two treatment strategies with VICTRELIS added to P/R to assess the ability of VICTRELIS to improve SVR rates and potentially shorten overall treatment duration, compared to the use of P/R alone for 48 weeks, which is the current standard duration of therapy.
In both studies, all patients receiving VICTRELIS were treated with a 4-week lead-in of peginterferon alfa-2b (1.5 mcg/kg/week) and an investigational dose of ribavirin (600-1,400 mg/day), followed by the addition of VICTRELIS (800 mg three times a day) after week 4.

In each study, patients were randomized to three groups:
  • Response-guided therapy (RGT), in which patients with undetectable virus (HCV-RNA) at treatment week 8 were considered early responders and were eligible for a shorter duration of therapy. Treatment-naïve patients with undetectable HCV-RNA during weeks 8 through 24 were eligible to stop all treatment at week 28. Treatment-failure patients with undetectable HCV-RNA at treatment weeks 8 and 12 were eligible to stop all treatment at week 36.
  • 48 weeks of treatment, in which patients received a 4-week lead-in with P/R followed by 44 weeks of VICTRELIS in combination with P/R.
  • Control, in which patients received P/R for 48 weeks. 
In the HCV RESPOND-2 study, all patients with detectable virus (HCV-RNA) at treatment week 12 were discontinued from treatment. In the HCV SPRINT-2 study, all patients with detectable virus (HCV-RNA) at treatment week 24 were discontinued from treatment.

The HCV RESPOND-2 study was conducted at U.S. and international sites, and included 403 adult patients who had failed prior treatment, including patients who relapsed or were partial responders to prior treatment with standard therapy. Historical null responders were not enrolled. Patients were randomized in a 1:2:2 ratio and stratified based on response to their previous qualifying regimen (relapsers vs. partial responders) and by HCV genotype (1a or 1b).

The HCV SPRINT-2 study was conducted at U.S. and international sites in 1,097 adult patients who were new to treatment. Patients were randomized in a 1:1:1 ratio within two separate cohorts (938 non-Black patients and 159 Black patients) and were stratified by HCV genotype (1a or 1b) and by HCV-RNA viral load (less than or equal to 400,000 IU/mL vs. greater than 400,000 IU/mL). Black patients with chronic HCV historically have been shown to be harder to treat successfully.

Final results of the HCV RESPOND-2 and HCV SPRINT-2 studies were published in the New England Journal of Medicine on March 31, 2011.

Important 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 and concomitant ribavirin. 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 that were treated with 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 untreated patients that were treated with 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 prescribing information

Dosing and administration
VICTRELIS must be administered in combination with peginterferon alfa and ribavirin. Therapy is initiated with peginterferon alfa and ribavirin for 4 weeks. Beginning in treatment week 5, VICTRELIS is added at a dose of 800 mg (four 200 mg capsules) orally three times daily (every 7-9 hours) with food (a meal or light snack). Based on the patient's virus (HCV-RNA) levels at treatment weeks 8, 12 and 24, dosing is adjusted using the following response-guided therapy guidelines.
  • Treatment-naive patients: Patients who are undetectable at treatment weeks 8 and 24 complete all therapy at treatment week 28. Patients who are detectable at treatment week 8, but undetectable at treatment week 24, complete VICTRELIS at treatment week 36 and continue on peginterferon alfa and ribavirin alone until treatment week 48.
  • Treatment-failure patients: Patients (previous partial responders or relapsers) who are undetectable at treatment weeks 8 and 24 complete all therapy at treatment week 36. Patients who are detectable at treatment week 8, but undetectable at treatment week 24, complete VICTRELIS at treatment week 36 and continue on peginterferon alfa and ribavirin alone until treatment week 48. Response-guided therapy was not studied in treatment-failure patients who had less than a 2 log decrease in virus (HCV-RNA) at treatment week 12 of prior treatment (null responders). If treated, these patients should receive 4 weeks of peginterferon alfa and ribavirin followed by 44 weeks of VICTRELIS in combination with peginterferon alfa and ribavirin.
Patients with compensated cirrhosis should receive 4 weeks peginterferon alfa and ribavirin followed by 44 weeks of VICTRELIS in combination with peginterferon alfa and ribavirin.

Patients who have HCV-RNA results greater than or equal to 100 IU/mL at treatment week 12 discontinue the three-medicine regimen. Patients who have confirmed detectable HCV-RNA at treatment week 24 discontinue the three-medicine regimen.

The wholesale acquisition cost (WAC) of VICTRELIS per week is $1,100.

About Merck
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Forward-Looking Statement

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The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck’s ability to accurately predict future market conditions; dependence on the effectiveness of Merck’s patents and other protections for innovative products; the risk of new and changing regulation and health policies in the U.S. and internationally and the exposure to litigation and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2010 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
Please see attached Prescribing Information and Medication Guide for VICTRELIS.

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.


1SVR, 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.

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