Washington Editor

CuraGen Corp.'s velafermin missed its primary endpoint in a Phase II trial, although positive trends were seen and the program will continue to move forward.

"We now have a better understanding of the population" Glenn Schulman, CuraGen's assistant director of investor relations, told BioWorld Today. "This was the first study done prospectively in this patient population. We are seeing single-dose activity with the product, which is very encouraging."

The company's stock slumped 23.6 percent on the revelation, as the shares (NASDAQ:CRGN) fell 98 cents to $3.18.

The top-line results failed to reach statistical significance on a predefined linear dose trend analysis that was the primary endpoint relative to the therapeutic's effect on preventing oral mucositis in high-dose chemotherapy patients, with or without total body irradiation, prior to autologous bone marrow transplantation.

Had the findings been perfect, Schulman said, Branford, Conn.-based CuraGen would have pushed the program into Phase III. Instead, additional Phase II work is scheduled to confirm and expand positive observations taken from the dose-ranging study.

The company emphasized the silver lining it found in the data, which showed a 50 percent reduction in grade 3 or 4 oral mucositis incidence in the 0.03 mg/kg velafermin dose arm compared to placebo. On a conference call, Tim Shannon, CuraGen's executive vice president of research and development and chief medical officer, said the results "were received positively" by study investigators and clinical advisers. Specifically, that dose produced an 18 percent incidence compared to a placebo incidence of 37 percent, a statistically significant difference (p=0.031).

"This was a well-designed, rigorously controlled study in this population where no data existed before," Schulman said. "There's a lot of valuable data, in terms of what the incidence of oral mucositis is for the general autologous bone marrow transplant population, and that's our goal: to develop this product as relevant to the patients and physicians who are treating them."

The U.S.-based study, which was conducted at about 20 sites, randomized 212 patients equally to receive one of three drug doses or placebo, including the 0.03 mg/kg dose that produced the positive trend. But that effect was not observed at the higher doses tested, 0.1 mg/kg and 0.2 mg/kg, a result that Shannon could not explain. But importantly, he said, "What we see in the clinic is that a single dose of velafermin seems to give a clinically meaningful effect in mucositis, and that's the observation we plan to build around going forward."

A preliminary 30-day safety analysis indicated that the product, also known as fibroblast growth factor-20 (FGF-20) or CG53135, appears to be safe and well-tolerated in this patient population, which numbers about 400,000 each year in the U.S., Shannon said.

Velafermin was administered one day after bone marrow transplantation, a different schedule than Thousand Oaks, Calif.-based Amgen Inc.'s Kepivance (palifermin), which was approved following a pivotal study that tested the keratinocyte growth factor in chemotherapy/radiation patients prior to transplant. It is given more frequently than velafermin, which has a different molecular makeup.

The CuraGen study's primary endpoint was the development of clinically significant grade 3 or 4 oral mucositis scored by the World Health Organization (WHO) Oral Mucositis Scale.

An evaluation of secondary endpoints included the duration of grade 3 and 4 oral mucositis, use of narcotic pain medications, time to neutrophil engraftment and the incidence and duration of diarrhea. More specific details on those analyses will be unveiled at a February scientific meeting in Hawaii, followed by further clarity on velafermin's further development.

Also going forward, CuraGen expects to complete a Phase I study by the end of this year testing velafermin for active oral mucositis in patients receiving high-dose chemotherapy, to decrease the condition's duration and progression, a treatment suggested by preclinical studies.

Separately, CuraGen and partner Copenhagen, Denmark-based TopoTarget A/S said Phase I data reported at the American Society of Hematology meeting in Atlanta showed that PXD101 was well tolerated following intravenous administration in the trial's 16 patients.

In terms of its efficacy, the small-molecule histone deacetylase inhibitor for advanced hematologic and solid cancers demonstrated potential anti-tumor activity against multiple myeloma, non-Hodgkin's lymphoma and transformed chronic lymphocytic leukemia.