DIGNA BIOTECH

IFN alfa 5

Interferons alfa -IFNs alfa- conform a family of proteins that include 13 different subtypes (named 1, 2, 4, 5, 6, 7, 8, 10, 13, 14, 16, 17, 21). These are molecules with antiviral, immunomodulatory and antiproliferative activity, induced naturally in the body in response to viral infections.

These interesting properties have positioned to this family of proteins as key molecules for the treatment of different pathologies. In fact, the combination of pegylated IFN alfa plus Ribavirin is the selected treatment for chronic hepatitis C infection.

Hepatitis C virus infection is notably by the tendency to develop chronicity, being the main cause of hepatic disease. 130 million people are chronically infected by the virus, which resembles that the virus has developed mechanisms particularly efficient to avoid the antiviral system. Current treatment consists in the combined administration of pegylated IFN alfa 2 and Rivabirin. Although main of patients infected with genotype 2 or 3 show a sustained virological response (SVR) to the current standard of care, only 50% of those infected with genotype 1 achieve SVR with this therapeutic strategy. As more than 80% HCV infected patients in Western world and Asia correspond to genotype 1, an increase in the efficacy of IFN alfa treatment is urgently needed.

Interferon alfa-5 (IFN ?-5) is the only interferon subtype that is produced in the liver of healthy people. Patients with HCV chronic infection had a significant decrease in the level of IFN-? expression (and so of IFN ?-5 as the subtype mainly expressed in hepatic tissue) as compared with healthy people of patients with other liver diseases (including hepatitis B virus chronic infection).

This led to the hypothesis that the use of IFN ?-5 might have advantages over the current use of IFN ?-2 in the treatment of chronic hepatitis C.

In experiments conducted with human hepatic cell lines (Huh7 and HepG2), IFN alfa 5 has shown consistently a higher ability for the induction of STAT1, STAT3 and Tyk2, as well as genes directly related to antiviral response as 2´-5´ OAS. All these data suggest that exogenous administration of IFN alfa 5 to HCV chronically infected patients might be very useful for the effective virus clearance.

IFN alfa 5 has been produced through recombinant DNA technology in E. Coli and a structural characterization and evaluation of physicochemical properties of purified IFN ?-5 protein were carried out.

A complete preclinical development program has been conducted including: pharmacodynamics, pharma and toxicokinetics, safety pharmacology and toxicological assessment.

IFN ?-5 has demonstrated to be safe. No abnormalities have been observed in laboratory analyses, tissue analyses, nor in the studies that have been conducted to observe its toxic effects in animals.

As a result the first phase I/II clinical trial entitled “A Phase I/II, Multicenter, Randomized, Open, Active-Controlled, Clinical Trial to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability Of Interferon Alfa 5, Administered S.C. 3 Times Per Week, For 29 Days, To Treatment-Experienced Patients with Genotype-1 Chronic Hepatitis C” was started in June 2010.

The objectives of this study are to compare safety, tolerability, early antiviral efficacy, pharmacodynamics and pharmacokinetics of IFN ?-5 administered alone or in a combination of IFN ?-5 and IFN ?-2. IFN ?-2b (Intron®) will be used as comparative. The maximum dose will be 3MUI each time.