By Jim Shrine


Rhone-Poulenc Rorer Gencell licensed rights to cardiovascular applications of the vascular endothelial growth factor B (VEGF-B) gene in a deal that could be worth up to $50 million for Amrad Corp. Ltd. and the Ludwig Institute for Cancer Research.

RPR Gencell will use an angiogenic approach to treating patients with atherosclerotic heart disease, after licensing patent rights held by Amrad, of Melbourne, Australia, and the Ludwig Institute, of Zurich, Switzerland.

RPR Gencell is the gene-therapy division of Collegeville, Pa.-based Rhone-Poulenc Rorer Inc.

Specific terms of the up-to-$50 million deal were not disclosed, although the companies said they entail license fees and milestone payments. A royalty component also is included.

Collateral Therapeutics Inc., of San Diego, had held rights to the VEGF-B gene since March 1997, but gave them up in September. At the time, the company said it had more than enough angiogenic genes to conduct research into non-surgical gene therapy products for cardiovascular indications.

RPR Gencell also is working with the FGF family of angiogenic genes. Its FGF-1 product is about to enter the clinic for peripheral artery disease, with delivery to veins around blockages in the leg.

"It's exactly the same principle [that is] being used for VEGF in the heart," said RPR Gencell spokeswoman Laura Hahn.

"Adding a VEGF product to our portfolio is part of our commitment to bringing this kind of technology to the marketplace," Hahn told BioWorld Today. "Having a VEGF product to go along with our FGF gene is very important to us."

Mary Ann Gray, a senior vice president at Raymond James & Associates Inc., said there are challenges to determining which gene to use, and how to deliver it - whether it's a protein directly to the heart or systemically throughout the circulatory system, or whether it's using vectors to the heart or through the blood. But Gray likes the approach.

"Gene therapy, in general, for angiogenesis is really an exciting field," said Gray, who is familiar with VEGF-B through her coverage of Collateral. "We have some anecdotal evidence the approach will work. Many of the different approaches have shown fairly striking results in different animal models.

"At this point there is no real way of knowing if any of these portions of the VEGF gene are going to be more or less effective than the others," Gray added.

Collateral also is working on an FGF approach. It has a Phase I/II trial ongoing of its Generx product, which uses an adenoviral vector with the FGF-4 gene, delivered through a catheter, to restore blood flow and heart function in patients with stable exertional angina due to coronary artery disease. The trial differs from most others in the field, in that it is double-blind and placebo controlled.

RPR Gencell's VEGF product still is in the preclinical stage. Hahn said it's unlike other members of the family because of the different receptors to which it binds, thus leading to a different biological response.