Flamel Technologies initiates IFN-alpha-2b XL Phase 2a clinical trial for HCV

Dec 18 2009

Flamel Technologies (NASDAQ:FLML) today announced the initiation of a Phase 2a clinical trial of Flamel’s Interferon alpha-2b XL (IFN-alpha-2b XL), which is based on Flamel’s Medusa^® platform for controlled release of biologics. IFN-alpha-2b XL is being developed as a controlled release of unmodified interferon alpha-2b for the treatment of chronic hepatitis C virus (HCV). This Phase 2a randomized study, known as ANRS HC 23 COAT-IFN (COnfirmation of Anti-viral activity and Tolerance of Interferon alpha-2b XL), is sponsored by the Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS). The Phase 2a study is designed to evaluate IFN-alpha-2b XL in combination with ribavirin in genotype-1 chronic hepatitis C patients who are either naïve to treatment or previous non-responders to standard interferon therapy (PEGylated interferon plus ribavirin).

The study will evaluate two doses of Interferon-alpha-2b XL (27 and 36 MIU) administered once a week for 12 weeks in combination with weight-based ribavirin in treatment-naïve and non-responder hepatitis C patients with genotype-1 HCV. The comparator arm of patients also comprises sub-groups of either treatment naïve or non-responder genotype-1 patients, each of which will be administered with PegIntron^® (1.5µg/kg) once a week for 12 weeks in combination with weight-based ribavirin. A total of 84 patients (28 patients by arm which will be equally split into naïve and non-responder patients) is expected to be enrolled in the trial. The study will assess viral response: the primary endpoint will be viral load reduction at week 4 and week 12. Investigators will also be looking at the percentage of patients achieving Rapid Virological Response, or RVR, defined as an undetectable viral load at week 4, and Early Virological Response, or EVR, defined as a viral load reduction greater than 2 log at week 12. Another endpoint that investigators will be assessing closely is the safety and tolerability data for both doses of Interferon-alpha-2b XL versus PegIntron. Results from the study will be used to select the doses of Interferon–alpha 2b XL for the pivotal confirmatory clinical trial.

Roger Kravtzoff, Flamel’s Director of Preclinical and Clinical Development commented: “We are very pleased to pursue the clinical development of this very promising product. Better safety and efficacy will be important outcomes for the next generation of interferon products, which we believe will continue to be part of the standard of care for HCV treatment, even with the advent of new small molecule drugs currently in clinical development. The potential benefits of IFN-alpha-2b XL have been highlighted by the results of the Phase 1b trial which indicated:

• Better tolerance, characterized by a marked reduction in side effects for patients given IFN-alpha-2b XL compared to those who received PegIntron; and
• Better antiviral activity, characterized by:
  • A statistically significant reduction in viral load for genotype-1 patients compared to similar patients who received PegIntron.
  • A marked reduction in viral load for “non-responder” patients compared to similar patients who received PegIntron.

If these results are confirmed in the COAT-IFN study using longer treatment, we believe that IFN-alpha-2b XL provides a better therapeutic option to treat patients.”

The principal investigator of the study, Professor Christian Trepo (Hôtel Dieu Hospital - Lyon), remarked: “The results of the prior phase 1b study were encouraging in that the most difficult to treat patients, namely genotype-1 non-responders, experienced a greater reduction in viral load when given 27 MIU of IFN-alpha-2b XL than patients administered the standard dose of PegIntron. Moreover, the trend we observed in the study suggests that the advantages of Interferon-alpha-2b XL with respect to viral load reduction are cumulative and may become more pronounced during the longer treatment regimens used in the COAT-IFN study.”

“This is especially positive, I believe, as these patients also experienced significantly fewer adverse events than patients in the comparator PEGinterferon group. Side effects associated with interferon treatment are debilitating and treatment limiting. Therapeutic outcomes are often negatively affected by the adverse events experienced by HCV carrier patients to the extent that dose reductions become necessary. Many patients may even choose to discontinue therapy. The previous Phase 1b results suggest that IFN-alpha-2b XL potentially provides at least equivalent and possibly better therapeutic benefits with fewer side effects in comparison to existing interferon-alpha based therapies. Indeed, entering the age of new anti-HCV molecules, what is most urgently wanted is the improvement of tolerance of the still needed interferon-alpha which is the number one hurdle of therapy. The confirmation of improved efficacy in the most hard to treat, genotype-1 non-responder patients will be most useful, especially in the future context of multiple therapies involving protease and polymerase inhibitors.”