Flamel Technologies Announces Positive Preliminary Results of a Phase I/II Trial of IFN-alpha-XL in Patients with Chronic Hepatitis C Virus Infection

Business Wire, Sept 23, 2005

LYON, France -- Flamel Technologies (NASDAQ:FLML) today announced positive preliminary Phase I/II data from a trial demonstrating the safety, tolerability, and long-acting activity of IFN-alpha-XL in patients with chronic hepatitis C virus (HCV) infection. Data also show that IFN-alpha-XL had positive effects on viral load and interferon activity biomarkers. IFN-alpha-XL utilizes Flamel's proprietary Medusa(R) nanoparticle technology to provide a long-acting formulation of interferon alpha that may have enhanced efficacy and reduced toxicity compared with unmodified or PEG-modified interferon formulations. Flamel plans to present the full data at a medical conference.

The lead investigator of the study, Professor Christian Trepo (Hotel Dieu Hospital-Lyon), remarked, "Interferon therapy is a cornerstone in the treatment of chronic hepatitis C infection, but today its use is limited by the significant side effects associated with approved formulations of Interferon-alpha. These side effects are debilitating and treatment limiting. The results of this first study of IFN-alpha-XL are very promising, and suggest that this novel formulation of interferon alpha may provide equivalent and possibly better therapeutic benefit with fewer side effects in comparison to existing interferon-alpha therapies. This would be a significant advance in the treatment of a disease that has reached pandemic proportions in the United States and around the world."

The dose-escalating study was conducted in 53 subjects with chronic hepatitis C. Thirty-nine participants were assigned to receive a single subcutaneous injection of one of three escalating doses of IFN-alpha-XL (12 - 14 patients per dose). The three IFN-alpha-XL groups received an injection of 9 million international units (MIU), 18 MIU, and 27 MIU, respectively. A cohort of 14 patients received three subcutaneous injections of a standard dose of Viraferon(R) (3 MIU) over one week as a comparator. All patients completed the study, and no serious adverse events were reported.

Adverse events were similar to what has been reported in other studies of interferon therapy and were transient in duration and mild to moderate in severity. Patients receiving IFN-alpha-XL appeared to have fewer adverse events than patients receiving Viraferon, which is marketed in the U.S. as Intron(R) A, even when the weekly dosage of IFN-alpha-XL was at its highest level. Pharmacokinetic data demonstrate that the Medusa formulation provides sustained release of IFN-alpha-XL over one week. Significantly, post-injection serum concentrations (Cmax) of IFN-alpha-XL were lower or equivalent than those observed for Viraferon. This is important in maintaining a concentration that provides therapeutic benefit while reducing side effects.

Dr. R. Kravtzoff, Director of preclinical and clinical development of Flamel Technologies, said: "We are very pleased with the preliminary results of this first clinical study of our long-acting Interferon alpha formulation, IFN-alpha-XL. The data demonstrate that IFN-alpha-XL was well tolerated and did not exhibit the toxicity typically observed with Interferon alpha 2b, even at the highest dose evaluated. The results indicate that reduction in viral load in these high-dose patients, including traditionally hard-to-treat genotype 1 cases, was at least equivalent to that observed in the control group. We are looking forward to sharing these results in greater detail at an upcoming medical conference."

Dr. Kravtzoff continued, "Patients with hepatitis C have significant unmet medical need, with only about half of patients treated with the current standard of care achieving a sustained, meaningful virologic response. We believe that IFN-alpha-XL may provide a new therapeutic option that would provide improved tolerance and patient compliance, leading to improved clinical outcomes."

Based on these clinical results Flamel Technologies is preparing a Phase IIa study in hepatitis C patients, while meeting with large pharmaceutical companies to explore partnership for this important program. A Phase IIa study would be designed to investigate the safety, duration of release and clinical efficacy of IFN-alpha-XL following repeated weekly administration in hepatitis C patients, compared with weekly administration of pegylated interferon alpha.

About IFN-alpha-XL

IFN-alpha-XL is a new formulation of recombinant Interferon alpha-2b based on Flamel's proprietary Medusa(R) nanoparticle delivery system. Medusa(R) is a versatile protein carrier for the development of novel and second-generation long-acting native protein drugs. IFN-alpha-XL is designed to provide patients with a longer acting and more tolerable approach to interferon therapy compared with approved interferon regimens.

About Hepatitis C

Hepatitis C virus is a blood-borne pathogen that causes inflammation of the liver. According to the U.S. Centers for Disease Control and Prevention (CDC) hepatitis C virus (HCV), more than 75 percent of people infected with HCV will develop chronic infections; and 60 to 70 percent of these people will subsequently develop chronic hepatitis. HCV infection is the most common blood-borne viral infection in the United States. Approximately 4 million people in the United States are infected with HCV and the World Health Organization estimates that 170 million people worldwide - 3 percent of the world's population - are infected with HCV.