Dutch biotechnology company Crucell N.V. said the results of its second clinical evaluation of rabies monoclonal antibody cocktail indicated that the cocktail is well tolerated, provides the expected neutralizing activity and that it can be safely administered in combination with a rabies vaccine.

The clinical trial was a randomised, double-blinded, placebo controlled study in healthy volunteers that tested the human monoclonal antibody cocktail against rabies alone, in a dose escalation design, as well as in combination with a rabies vaccine. In the first, blinded, part of the study, in which solely the antibody cocktail was given, rabies virus neutralizing activity could be demonstrated at both dose levels that were administered. In the second, open, part of the study, in which the rabies antibody cocktail was administered in combination with a rabies vaccine, all volunteers seroconverted within 14 days upon the initiation of treatment. A level of rabies virus neutralizing activity was achieved that is considered to provide protection against the deadly virus, thus proving that the antibody cocktail can be safely co-administered in line with standard therapy.

Data for the phase Ib study conducted in India which started in April 2007 are presented by Dr Christophe Python, at the Joint International Tropical Medicine Meeting 2007 in Bangkok, Thailand.

The data from the Indian study confirm and extend the results of the first-in-human phase I study conducted in the US, which was presented on 3 October 2007 at the XVIII Rabies in the Americas RITA conference in Mexico. The combined data from both phase I studies prompt the progression towards phase II studies which are expected to start in the first half of 2008 in the US and the Philippines.

"The positive results from both studies, together with the fast track designation for this antibody cocktail which we were awarded just recently, supports our commitment to moving as fast as possible to address the unmet medical need that exists for rabies," said Dr Jaap Goudsmit, chief scientific officer.

On 13 November 2007, Crucell announced that it had been granted Fast Track designation for its rabies antibody cocktail by the Food and Drug Administration's (FDA) Department of Health and Human Services. The Fast Track program facilitates the development and expedites the review of new drugs that are intended to treat serious or life-threatening diseases and that demonstrate the potential to address unmet medical needs.

Crucell is developing the rabies antibody cocktail for the post-exposure prophylaxis of rabies. The antibody cocktail is a combination of two human monoclonal antibodies and is produced with the use of Crucell's MAbstract and PER.C6 technologies. Based on market needs, peak sales for Crucell's rabies antibody cocktail are expected to exceed US$ 300 million.

Crucell has already contracted DSM Biologics, its alliance partner for the PER.C6 technology platform, for the process validation and manufacturing of antibody batches for phase III clinical efficacy studies.

Rabies is a viral disease of mammals most often transmitted through the bite of a rabid animal. The virus infects the central nervous system, causing encephalitis (inflammation of the brain) and ultimately death if medical intervention is not sought promptly after exposure. There is no proven treatment for rabies once symptoms of the disease have appeared. Lethal rabies is prevented by post-exposure prophylaxis (PEP) via the combined administration of a rabies vaccine and RIG following the bite of a rabid animal. Current supply and quality of rabies vaccine is sufficient, but RIG is in short supply and carries certain safety risks.

Rabies is prevalent in Europe, Asia, North and South America as well as Africa. Every year, approximately 10 million people are vaccinated worldwide. With the exception of the US and Europe, most of these people do not receive RIG due to shortages and are therefore not adequately protected. As a result, an estimated 40,000 to 70,000 people die of the disease each year, mainly in Asia.

Crucell develops the antibody cocktail using its PER.C6 technology, which offers large-scale manufacturing capabilities and production under serum-free culture conditions. Crucell's rabies monoclonal antibody cocktail offers the potential for replacing the traditional serum-derived products that are currently still used for the treatment of rabies. Based on market needs, peak sales for Crucell's cocktail are expected to exceed US$ 300 million.

Crucell's PER.C6 technology is a cell line developed for the large-scale manufacture of biopharmaceutical products such as recombinant proteins including monoclonal antibodies. Compared to conventional production technologies, the strengths of the PER.C6 technology lie in its excellent safety profile, scalability and productivity under serum-free culture conditions.