| |
Flamel Technologies Announces Positive Preliminary Results of a Phase I/II Trial of IFN-alpha-XL in Patients with Chronic Hepatitis C Virus Infection
|
| |
| |
LYON, France--(BUSINESS WIRE)--Sept. 23, 2005--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 design of the Medusa® "polypeptide-like" aminoacid polymers allows a non-covalent capture and subsequent delivery of native peptide or protein drugs.
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.
http://www.flamel.com/techAndProd/medusa.shtml
Flamel's Medusa® technology consists of naturally occurring aminoacids (Leu hydrophobic and Glu hydrophilic), which form stable nanoparticles spontaneously in water. The amphiphilic character of the poly-aminoacid polymers drives the self-assembling of the nanoparticles in water; the poly-Leu chains are packed inside the structure, whereas those of Glu aminoacids are exposed to water. The nanoparticles, which are 20-50 nanometers in diameter, are composed of 95% water and 5% Leu-Glu polymer. They are robust over a wide range of pH values and can be stored as either stable liquid or stable dry forms.
Once injected in the body, the nanoparticles release the captured-drugs in a controlled manner and over an extended period of time. Both processes (capture and release) are non-denaturing, which preserves structural integrity - and hence the biological activity - of the drug. The transient non-covalent interactions dictate the pharmaco-kinetic profile (Cmax and AUC, in particular) of the released drugs.
Performance
* Reduces 5- to 10-fold the intensity of the peak (i.e., the maximal concentration or Cmax) after administration, which is the cause of intense side-effects;
* Maintains the concentration of native protein drugs (integrity of the drug structure preserved) for at least two weeks or more (in dog models), offering a long duration of action with improved efficacy;
* Improves the compliance of the treatment with a twice-a-month and, in some cases, once-a-month regimen; and,
* Improves the solubility-viscosity of insoluble protein drugs (e.g. IL-2).
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.
Current treatment regimens require frequent administration of Interferon-alpha for periods of several months to a year or longer. Thus, frequent dosing of Interferon-alpha has been considered necessary for sustained efficacy. Furthermore, treatment with Interferon-alpha is associated with dose-dependent adverse events that can be classified as either acute or of later onset. The typical acute toxicity profile tends to occur after every injection and thus causes difficulties for repeated administration. The decrease of Interferon-alpha side effects, especially long-term side effects such as psychological depression and myelosuppression, the decrease of frequency of administration, and the improvement of clinical efficiency, are thus major issues for Interferon-alpha based therapy.
Flamel Technologies, S.A. is a biopharmaceutical company principally engaged in the development of two unique polymer-based delivery technologies for medical applications. Micropump(R) is a controlled release and taste- masking technology for the oral administration of small molecule drugs. Flamel's Medusa(R) technology is designed to deliver controlled-release formulations of therapeutic proteins.
This document contains a number of matters, particularly as related to the status of various research projects and technology platforms, that constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.
This document reflects the current view of management with respect to future events and is subject to risks and uncertainties that could cause actual results to differ materially from those contemplated in such forward-looking statements.
These risks include risks that products in the development stage may not achieve scientific objectives or milestones or meet stringent regulatory requirements, uncertainties regarding market acceptance of products in development, the impact of competitive products and pricing, and the risks associated with Flamel's reliance on outside parties and key strategic alliances.
These and other risks are described more fully in Flamel's Annual Report on the Securities and Exchange Commission Form 20-F for the year ended December 31, 2004.
Viraferon(R) and Intron(R) A are registered trademarks of Schering-Plough Corporation.
Contacts
Flamel Technologies, S.A.
Stephen H. Willard, 202-862-8400
Fax: 202-862-3933
E-Mail: Willard@flamel.com
or
Charles Marlio, 011-33-472-78-3423
Fax: 202-862-3933
E-Mail: Marlio@flamel.com
or
Business Development:
Andy Francis
Tel: (33) (4) 7278-3434
Fax: (33) (4) 7278-3435
E-Mail: Francis@flamel.com
|
|
| |
| |
|
|
|
