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)
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.
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.
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.