Pill burden and HCV Direct Acting Antivirals....

While Victrelis and Incivek are major game changing drugs in the treatment of Hepatitis C, it’s critical to remember that adherence to the entire regimen, not just the protease inhibitor, is essential to achieving and SVR and avoiding resistance.

NEW YORK, NY — 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."

Kadmon and Valeant ink global deal on ribavirn and taribavirin....

Valeant Pharmaceuticals and Kadmon Pharmaceuticals inked two separate agreements, worth a combined $12.5 million up front, covering the development and/or marketing of the hepatitis C drug ribavirin and the clinical-stage ribavirin prodrug candidate taribavirin. The deals come within a few days of Kadmon buying out Three Rivers Pharmaceuticals, which already markets the hepatitis C drugs Infergen™ (consensus interferon), Ribasphere® (ribavirin, USP), and RibaPak® (ribavirin).

The first new deal gives Kadmon an exclusive, worldwide license (excluding Japan) to taribavirin, which has successfully completed a Phase IIb trial for the treatment of chronic hepatitis C. Under terms of this agreement Kadmon will pay Valeant $5 million up front in addition to development milestones and future sales royalties.

The second agreement gives Valeant exclusive rights to all Kadmon dosage forms of ribavirin, including its 200 mg, 400 mg, and 600 mg capsules and tablets, in Poland, Hungary, the Czech Republic, Slovakia, Romania, and Bulgaria. Valeant paid Kadmon $7.5 million for the ribavirin portfolio and will source the products from Kadmon.

At first glance the combination of these two deals may seem counterintuitive. Valeant is passing further development of its ribavirin prodrug candidate virtually worldwide to Kadmon but is instead taking on rights to a marketed ribavirin portfolio in central Europe. However, as Valeant’s CEO, J. Michael Pearson, points out, while further development of taribavirin in house was halted in 2009 until a partner could be found, the firm wants to keep its hand in the branded generics market for hepatitis C drugs in some territories. “While participating in product development in the overall hepatitis C market no longer fits within our corporate development strategy, ribavirin could be a significant product for our branded generics portfolio in Central Europe.”

Kadmon, meanwhile, is making a more obvious push into the hepatitis C market globally, both through its deal with Valeant and with its recent acquisition of Three Rivers. “Kadmon is building upon its commercial platform in hepatitis C through expanded global distribution and the addition of complementary products,” notes Samuel D. Kalsal, CEO. “Our agreements with Valeant achieve milestones for both of these objectives. Taribavirin completes our ribavirin franchise and will ensure its future sustainability and growth. We have also expanded our global distribution network for ribavirin into markets in which Valeant is a leading provider.”