PARIS - Genzyme Biosurgery, a subsidiary of Genzyme Corp., signed agreements on Monday with a French biotech start-up, Myosix SA, and the Paris Public Hospital Authority to conduct a large-scale Phase II trial of a cell therapy for heart failure developed by French medical researchers.

The multicenter trial is to be carried out on 300 patients in France, other European countries, the U.S., and possibly Japan starting this fall, and will be by far the largest clinical trial ever conducted of a cell therapy.

The therapy is designed to improve a patient's heart function after heart attack through the introduction of muscle cells from another part of the body into the damaged areas of the heart. It entails the removal of autologous skeletal myoblasts from the patient's leg, culturing them to increase their numbers (to between 400 million and 1 billion) and then injecting them into the heart during a coronary artery bypass operation. Myoblasts are dormant cells found in muscle tissue that begin dividing only when muscle injury occurs.

The technique was developed by Jean-Pierre Marolleau and Jean-Thomas Vilquin and was jointly patented by the Paris Public Hospital Authority (AP-HP) and the French National Institute for Health and Medical Research (INSERM). In 2000, Marolleau and Vilquin created their own Paris-based company, Myosix, to exploit the patent for which it has an exclusive license. Myosix has now granted Genzyme Biosurgery, of Cambridge, Mass., a sublicense for the North American market.

The therapy was validated in a Phase I trial carried out on 10 patients at the Saint Louis hospital in Paris between June 2000 and November 2001. The medical team was led by Philippe Menasché, who also will be principal investigator for the Phase II trial. This will aim to establish not only the safety and efficacy of the therapy but also its overall clinical benefit, said Duke Collier, the president of Genzyme Biosurgery.

The studies in France will be co-financed by AP-HP, which has budgeted about $1.3 million for the purpose, and Genzyme, which also will finance the trials elsewhere. That will add up to an investment of "several million dollars" for the company, Collier said at a press conference in Paris.

In addition, Genzyme will handle much of the cell-culture operations in cooperation with the Saint Louis hospital. Between them, they are developing a standardized procedure based on the one used by Myosix, but also drawing on the industrial-scale cell manipulation expertise of Genzyme. The U.S company also assisted in the design of the protocol for the Phase II trial, which Collier said was based on "more sophisticated endpoints than the Phase I study."

He told BioWorld Today that the clinical development of the therapy as far as the regulatory approval stage would cost at least $50 million to $100 million, adding that "the cost could be a lot higher than that depending on the regulatory environment." He also said that Genzyme would be prepared to invest in manufacturing facilities in France if the product reached the market, pointing out that the company had "options to acquire commercialization rights for the rest of the world." Genzyme has had a presence in France for over 10 years and currently employs around 100 people there (and 1,000 in Europe as a whole).

Menasché, whom Collier described as the "demonstrable leader in the area of cardiac cell therapy" on the strength of his preclinical and clinical work, sought to play down expectations. "We are at the beginning of the beginning of the beginning as far as cell therapy is concerned," he said. "In no way could you say that cell therapy is a miraculous cure which will replace conventional treatment. It is only one option among others."