New Hepatitis C Combination Therapy Looking Good
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This press release has more encouraging news for those of us waiting for a more potent and less toxic treatment for Hepatitis C, genotype 1.
Current therapy is least effective for this genotype. Genotype 1 is the most prevalent in the US, Europe and Japan. It is estimated that 70% of Americans are infected with genotype 1 (a or b).
More and more drug therapies are under development as pharmaceutical companies scramble to get a piece of this multi billion dollar market.
While this treatment is still in fairly early stages of testing, the results are nonetheless encouraging.
Encouraging Interim Results of Phase II Study of Valopicitabine (NM-283) in Combination with Peginterferon Alfa in Patients with HCV Genotype 1
The double combination of valopicitabine (NM-283) plus peginterferon alfa produced a 99.94 percent (3.2 log10) mean reduction of HCV RNA (viral load), according to interim results of a Phase II clinical study in treatment-naïve patients with HCV genotype 1. Indenix Pharmaceuticals announced results of the interim analysis, which include data on 19 patients who have completed 12 weeks of combination treatment with valopicitabine plus peginterferon alfa.
Nine of 12 patients receiving combination therapy in this small study experienced an early viral response (EVR) with a greater than 2 log10 decrease in levels of HCV RNA at week 12. No serious adverse events have been reported so far. To date, valopicitabine has demonstrated a satisfactory safety profile with mild to moderate gastrointestinal side effects and no treatment-related discontinuations.
There is a pressing need for more potent and less toxic therapies for the treatment of chronic hepatitis C, especially for individuals with HCV genotypes 1 or 4, who are difficult to treat successfully. Among patients with these two HCV genotypes, only about 50% achieve a sustained virological response (SVR) from use of the current standard of care, peginterferon alfa in combination with ribavirin. Novel new compounds such as valopicitabine offer hope for better outcomes from combination treatment in the future.
An oral nucleoside analog, valopicitabine is Idenix Pharmaceuticals’ lead drug candidate for the treatment of hepatitis C. Now under development in combination with peginterferon alfa, valopicitabine was co-discovered by Idenix and the University of Cagliari through a cooperative laboratory agreement under the direction of Dr. Paolo LaColla, Director of the Department of Biomedical Sciences and Technologies of the University.
“In patients infected with HCV genotype 1 – a difficult-to-treat strain of hepatitis C virus and the most prevalent strain in the U.S., Western Europe and Japan – virologic response to the current standard therapy of ribavirin and peginterferon alfa is inconsistent,” commented Nathaniel Brown, M.D., Idenix’s executive vice president, clinical development and chief medical officer. “However, the consistency of response to the combination of valopicitabine and peginterferon alfa appears promising: eleven of twelve patients receiving this combination treatment had significant HCV RNA reductions of 1.7 to 6.2 log10 by week 12.
Phase IIa Trial Design and 12-Week Interim Results
Based on these encouraging interim data, Idenix will enroll a total of 30 patients in the phase IIa clinical trial, which is designed to assess the safety, antiviral activity and pharmacokinetics of the combination of valopicitabine and peginterferon alfa compared to valopicitabine alone. Key entry criteria for this clinical trial include treatment-naïve patients with HCV genotype 1, baseline viral load greater than 5 log10 copies/ml and alanine aminotransferase (ALT) levels less than 5 times the upper limit of normal.
In this phase IIa clinical trial, patients are being randomized to one of two treatment arms so that 12 patients will receive valopicitabine monotherapy and 18 patients will receive valopicitabine plus peginterferon alfa.. After 12 weeks of treatment, mean HCV RNA reductions from baseline were 0.9 log10 IU/mL, or 87.4 percent, for the 7 patients in the NM283 monotherapy group, and 3.2 log10 IU/mL, or 99.94 percent, for the 12 patients in the combination treatment group.
Nine of twelve patients receiving combination treatment have achieved an early viral response with a greater than 2 log10 decrease in levels of HCV RNA at week 12. Tolerance of both treatment regimens has been satisfactory to date, with no serious adverse events.
Four-week data from a study of these same 19 patients were presented by Dr. Nezam Afdhal at the annual meeting in November 2004 of the American Association for the Study of Liver Diseases (AASLD 2004).
About Hepatitis C
There are approximately 170 million people worldwide with chronic HCV infection, of which approximately 2.7 million are in the United States. Chronic HCV infection accounts for 40 percent of end-stage cirrhosis, 60 percent of liver cancer and 30 to 40 percent of liver transplants in the United States and other industrialized countries.
Responses to current treatment options are frequently inadequate due to the inability of some patients to tolerate these treatments and by their limited effectiveness, particularly in patients infected with HCV genotype 1. The genotype 1 strain of HCV is the most treatment-resistant HCV genotype and is estimated to cause more than 70 percent of the reported cases of hepatitis C in the U.S. and Japan, and more than 65% of the reported cases of hepatitis C in Western Europe.
Hepatitis C Drug Development Program at Idenix
Idenix’s hepatitis C development program is initially seeking to address the large patient population that has failed to respond to the current standard treatment, peginterferon alfa plus ribavirin, and for whom no other treatment option is currently available. Idenix expects to subsequently target the treatment-naïve patient population for whom treatment with the current standard of care is only successful in approximately 50% of patients.
“Hepatitis C patients confront many unmet treatment needs, with several hundred thousand having failed prior treatment with no therapeutic options, and millions of people infected with difficult to treat strains of HCV,” said Jean-Pierre Sommadossi, Ph.D., Idenix’s chairman and chief executive officer. “Idenix is committed to rapidly advancing the valopicitabine clinical program, which seeks to address the medical needs of all individuals infected with hepatitis C.”
Drug Development for Patients Who Experience Treatment Failure
Idenix has initiated a Phase IIb clinical trial for valopicitabine in patients who have previously failed peginterferon alfa and ribavirin and expects to begin enrolling patients in this study in early 2005. The company anticipates that this 6-month head-to-head trial, comparing the combination of valopicitabine plus peginterferon alfa to the current standard therapy (ribavirin plus peginterferon alfa), will enroll approximately 170 HCV genotype 1 patients who have previously failed at least 3 months of treatment with current standard therapy. The Phase IIb clinical trial will also include a monotherapy arm of valopicitabine.
Drug Development for Treatment-naïve Patients
Encouraging results from the ongoing Phase IIa clinical trial, summarized above, will support initiation of a larger Phase IIb clinical trial of valopicitabine in combination with peginterferon alfa in treatment-naïve patients, the majority of whom are expected to be infected with HCV genotype 1. Idenix anticipates beginning this trial in mid-2005.
About Idenix
Idenix Pharmaceuticals, Inc. is a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral and other infectious diseases. Idenix’s current focus is on the treatment of infections caused by hepatitis B virus, hepatitis C virus and human immunodeficiency virus (HIV). Idenix’s headquarters are located in Cambridge, Massachusetts and it has drug discovery operations in Montpellier, France and Cagliari, Italy.
Safety, Activity and Pharmacokinetics of the Combination of New Anti-HCV Compound NM-283 Plus Pegylated Interferon
For further information about Idenix, visit http://www.idenix.com/
01/19/05
Source
IDENIX REPORTS INTERIM ANALYSIS OF A PHASE IIA CLINICAL TRIAL OF VALOPICITABINE (NM283) IN COMBINATION WITH PEGYLATED INTERFERON IN TREATMENT-NAÏVE HEPATITIS C GENOTYPE 1 PATIENTS. Press Release. January 10, 2005.
