By Randall Osborne
West Coast Editor
Genzyme Biosurgery was expected to take the wraps off its quietly developing cardiovascular gene therapy program over the weekend, describing at a scientific meeting its ongoing Phase I trials with an engineered form of the HIF-1a gene for angiogenesis.
In preclinical studies, the gene has been shown to activate expression of proteins associated with blood vessel formation, and Genzyme Biosurgery, a division of Cambridge, Mass.-based Genzyme Corp., has three sets of clinical trials under way.
Ralph Kelly, vice president for clinical research at Genzyme Biosurgery, was slated to talk about the gene therapy Sunday.
¿As far as we know, all the other [gene therapies] out there, except one in animal development, involve a single growth factor,¿ he told BioWorld Today.
Genzyme¿s version of HIF-1a, however, turns on expression of angiogenic proteins in addition to vascular endothelial growth factor, or VEGF, and so it may work longer and stronger than gene therapies based on a single growth factor, the company said. Genzyme licensed HIF-1a exclusively in gene therapy from Johns Hopkins University.
The company expects to enroll 20 patients in a U.S. trial, and 28 in a European trial, in which a genetically engineered form of HIF-1a is administered to patients with coronary artery disease undergoing bypass surgery who have an area of the heart that is not suitable for surgical revascularization.
Another U.S. trial, in which the HIF-1a gene is delivered to the affected legs of patients with severe peripheral arterial disease, has enrolled 20 of 28 patients so far.
¿The next step [after the severe disease] is amputation, and this is the trial where we¿re farthest along,¿ Kelly said. ¿We¿ve gone through several cohorts, and reached the highest dose. We hope to finish enrollment by January.¿
Multiple trials were undertaken because of fallout from a much-publicized gene therapy death in September 1999, Kelly said.
¿Everything slowed to a crawl after that, and we were uncertain if we would get approval [to go ahead with trials in the U.S.],¿ he said. ¿We decided we would also go down the European route.¿ Ultimately, the FDA ¿had issues, but no show-stoppers, and we got permission sooner than we anticipated. By that time, we had already gotten approval at several centers in Europe.¿
The company went ahead with the peripheral arterial disease trial first, ¿even though our heart is really in the heart, as it were,¿ Kelly said, adding that ¿it¿s a very large market, although not quite as sexy as cardiovascular disease.¿
Genzyme is still investigating how HIF-1a works, and experiments are yielding curious results. The gene apparently turns on human b-type natriuretic peptide, or BNP, a genetically engineered form of which has been approved by the FDA in the form of Natrecor (nesiritide), developed by Scios Inc., of Sunnyvale, Calif.
Kelly said Genzyme is jumping to no conclusions immediately, but ¿it gave us a warm, fuzzy feeling,¿ and more discoveries may yet be made.
In the HIF-1a trials, researchers are using a second-generation adenovirus.
¿It¿s the viral backbone used in those [cystic fibrosis trials, begun by Genzyme in 1992], so we have a lot of data on the safety profile,¿ Kelly said, adding that those trials were discontinued but ¿we learned a lot.¿
Genzyme Biosurgery¿s stock (NASDAQ:GZBX) closed Friday at $5.94, down 30 cents.