Romark Announces Data From Clinical Trial of Nitazoxanide in Treatment-Naive Patients With Genotype 1 Chronic Hepatitis C

TAMPA, Fla., April 15 /PRNewswire/ -- Romark Laboratories announced results from its STEALTH C-3 clinical trial, a phase 2 clinical study of nitazoxanide in treatment-naive patients with genotype 1 chronic hepatitis C.  Study results were presented as a late breaking communication at the International Liver Congress™ 2010, the 45th Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria.

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The study was a randomized, double-blind, placebo controlled trial conducted at thirteen centers in the United States in patients with genotype 1 chronic hepatitis C, 35% of whom had advanced stage 3 or 4 fibrosis.  A sustained virologic response (undetectable HCV RNA) twelve weeks after the end of treatment (SVR12) occurred in 44% of patients treated with nitazoxanide (500 mg twice daily) plus standard therapy (Pegasys® and Copegus®, F. Hoffman LaRoche) for 48 weeks versus 32% of patients treated with placebo plus standard therapy. SVR12 rates were consistently higher in subsets of patients with high baseline viral load (41% vs. 29%) and in African Americans (38% vs. 20%).  Safety analyses showed no adverse events attributable to nitazoxanide, with the exception of mild to moderate intermittent diarrhea and discolored urine. Final results of this study will be presented at a late breaking forum of the American Gastroenterological Association Institute during Digestive Disease Week in May of this year.

Results of the STEALTH C-3 study are consistent with previously reported data from studies of nitazoxanide plus Pegasys® and Copegus® in treatment-naive patients with genotype 4 chronic hepatitis C.(1,2,3)  The STEALTH C-3 study is the first trial of nitazoxanide in treatment-naïve patients with genotype 1 chronic hepatitis C.

"We are pleased to achieve these results in a population representative of the broad range of hepatitis C patients in the United States, including 35% with advanced fibrosis," said Jean-Francois Rossignol, M.D., Ph.D., Chairman and Chief Science Officer of Romark and inventor of the drug.  "We plan to initiate phase 3 clinical trials of nitazoxanide using our 675 mg controlled release tablets in combination with peginterferon with or without ribavirin later this year.  The 675 mg controlled release tablets deliver a higher dose of nitazoxanide with a better pharmacokinetic profile.  Additional clinical trials using the 675 mg controlled release tablets in genotype 1 and 4 patients are underway and include reduction of the duration of peginterferon to 24 weeks with and without ribavirin.  We also plan to investigate combinations with direct acting antiviral drugs.  Because of its novel mechanism and very  favorable safety profile, we expect nitazoxanide to play an important role in a broad range of patients with chronic hepatitis C."

Nitazoxanide is the first of a new class of broad spectrum antiviral drugs called the thiazolides.(3,4,5)  It is a potent inhibitor of hepatitis C virus in replicon studies,(4) and studies have shown that it does not induce viral mutations that confer drug resistance.(5)  Nitazoxanide is synergistic with interferon and direct acting antivirals.(4,6)  In patients with chronic hepatitis C, the addition of nitazoxanide has not resulted in an increase in the toxicity associated with peginterferon and ribavirin. Studies in patients with genotype 4 chronic hepatitis C suggest that nitazoxanide can be used to replace ribavirin.(1,2)   The AIDS Clinical Trials Group (ACTG) in the United States is studying nitazoxanide plus peginterferon and ribavirin for treating chronic hepatitis C in patients coinfected with HIV.

"Patients with chronic hepatitis C are diverse in many respects with patient and virus characteristics that affect treatment outcomes (HCV genotype, viral load, stage of liver disease, IL28B genotype, race, body weight, coinfection with HIV or hepatitis B virus, and ability to tolerate treatment)," said Emmet B. Keeffe, Chief Medical Officer of Romark Laboratories.   "The trend in therapy of chronic hepatitis C has been toward individualized therapy with combinations of antiviral drugs.  There is a need for a new class of safe drugs with novel mechanism that can be used in combination with current standard therapy or with other new classes of drugs to improve treatment outcomes.  We believe nitazoxanide can play an important role in these combinations."

Another communication of late-breaking data related to use of nitazoxanide plus standard therapy in patients with genotype 1 chronic hepatitis C who previously failed to respond to peginterferon plus ribavirin is scheduled for Saturday, April 17.  In keeping with the embargo policy of the conference, the title and authors of the abstract on the nonresponder study are as follows:

Title: Phase 2  Randomized, Double-Blind, Placebo-Controlled Study of Nitazoxanide with Peginterferon Alfa-2a and Ribavirin in Nonresponders with Chronic HCV Genotype 1: Final Report

Authors: M.L. Shiffman,(1) A. Ahmed,(2) I.M. Jacobson,(3) R.E. Pruitt,(4) E.B. Keeffe,(2,5) and STEALTH C-2 Investigators. (1)Liver Institute of Virginia, Bon Secours Health System, Newport News, VA, USA  (2)Stanford University Medical Center, Stanford, CA, USA  (3)Weill Cornell Medical College, New York, NY, USA, (4)Nashville GI Specialists, Nashville, TN, USA  and (5)Romark Institute for Medical Research, Tampa, FL, USA

About Hepatitis C

Hepatitis C is a blood-borne infectious disease that is caused by the hepatitis C virus (HCV). It is the most common cause of chronic hepatitis in the U.S. and may eventually lead to cirrhosis, liver cancer and liver failure. The disease is transmitted by contact with HCV-infected blood.  A large majority of those infected do not show symptoms, but fatigue, abdominal pain and nausea can be common.  The current standard treatment of care, peginterferon and ribavirin, is effective in about half of all patients treated. Treatment outcomes vary based on a number of factors including genotype, viral load, genetic factors, stage of liver disease, co-infections and ability to adhere to treatment.  According to the Centers for Disease Control, HCV affects an estimated 3.2 million Americans.

About Romark Laboratories

Romark  Laboratories, L.C. (www.romark.com) is a biopharmaceutical company committed to the discovery and development of innovative new small molecules for treating infectious diseases and cancers.

1  Rossignol JF, Elfert A, El-Gohary Y, et al. Improved virologic response in patients with chronic hepatitis C genotype 4 treated with nitazoxanide plus peginterferon alfa-2a with or without ribavirin. Gastroenterology.  2009;136:856-862.

2  Rossignol JF, Elfert A, Keeffe EB.  Treatment of chronic hepatitis C using a 4-week lead-in with nitazoxanide before peginterferon plus nitazoxanide. J Clin Gastroenterol. In press.

3  Rossignol JF, La Frazia S, Chiappa L, Ciucci A, Santoro MG. Thiazolides, a new class of anti-influenza molecules targeting viral hemagglutinin at the post-translational level. J Biol Chem 2009; 284:29798-29808.

4  Korba BE, Montero AB, Farrar K, et al. Nitazoxanide, tizoxanide, and other thiazolides are potent inhibitors of hepatitis B virus and hepatitis C virus replication. Antivir Res. 2008;77:56-63.

5   Korba BE, Elazar M, Lui P, et al. Studies of the potential for hepatitis C virus resistance to nitazoxanide or tizoxanide. Antimicrob Agents Chemother. 2008;52:4069-4071.

6 Korba BE, Elazar M, Liu P, et al. Potential role for nitazoxanide in combination with STAT-C agents for the inhibition of HCV replication without the development of resistance. Hepatology. 2008;48(suppl):356A.

SOURCE Romark Laboratories, L.C.