By Jim Shrine
Sugen Inc. plans to cut off a year or more from the development time line of its angiogenesis inhibitor, SU5416, by going directly from safety and other early studies into pivotal trials in three indications.
The South San Francisco company's plan, pending FDA approval, calls for getting Phase III studies started in the second or third quarter of this year in lung cancer, colorectal cancer and AIDS-related Kaposi's sarcoma.
Peter Hirth, Sugen's executive vice president, drug research and development, told BioWorld Today that Phase I studies included enough patients who were treated for a long enough time, and with a number of escalating doses, so that a lot already is known about SU5416.
"We figured we would learn very little in a Phase II study that would have an impact on that critical path to registration," Hirth said. "Phase II is not really meant to be powered to get statistically significant results. The best you can get is trends in activity. In a way our Phase I study looks more like a Phase I/II."
Kevin Kwok, Sugen's director of corporate affairs and business development, said, "One has to look at risk-reward and also the paradigm of commercializing a cytostatic drug. We know the drug is safe; we've seen that in close to 100 patients.
"We think the risk-reward of going on an accelerated path will be good from two standpoints," Kwok told BioWorld Today. "One is a better time to market. The ability to jump directly into Phase III could save a year, maybe more. The second is we would conduct trials that would be meaningful in a way that the product will be used clinically."
Expected to be built into the lung and colorectal cancer studies are interim analyses, when the equivalent of Phase II data will be analyzed. Hirth said that interim data could be ready for review in the first half of 2000.
Specific designs have not been finalized, but Hirth expects the colorectal and lung cancer studies each will include 350 to 400 patients. Each also will compare the combination of standard chemotherapy regimens and SU5416 against the chemotherapy regimens alone.
"We think this is a reasonable and well-justified strategy," Hirth said. "Our Phase I was really a Phase I/II in that it had a large number of patients enrolled. We have quite a database in terms of safety for long durations of treatment. The longest was over a year."
KS Results Expected Sooner
The Kaposi's sarcoma study will be simpler, since objective responses are easy to document and usually are seen after several weeks. Sugen anticipates a one-arm study in KS with 60 to 80 patients.
SU5416 is a small-molecule inhibitor designed to prevent formation of new blood vessels needed for tumor growth by blocking the signaling pathway of the Flk-1/KDR receptor found in endothelial cells of blood vessels.
The drug is partnered in Japan with Taiho Pharmaceutical Ltd., of Osaka, which will help fund the Phase III trials. The collaboration potentially is worth $70 million to Sugen, which retained rights in the rest of the world. Sugen intends to keep rights in North America. (See BioWorld Today, July 31, 1998, p. 1.)
SU5416 will be Sugen's second cancer drug in trials designed to support registration. The small molecule SU101 - a platelet-derived growth factor inhibitor - is in Phase III in refractory glioma. An interim analysis is expected this fall. And SU101 is scheduled to be tested this year in a Phase III trial in hormone-refractory prostate cancer.
Sugen's stock (NASDAQ:SUGN) gained 25 cents per share Wednesday to close at $14.562. n