National Editor

With a new CEO installed and a recent favorable court ruling, SangStat Medical Corp. chalked up more good news Wednesday: positive preliminary Phase II data with RDP58, its drug for ulcerative colitis.

The outcome of the trial was less positive for patients with Crohn's disease, in whom no statistically significant response was shown. But the company's shares (NASDAQ:SANG) closed Wednesday at $13.33, up $2.48, or 22.9 percent.

"We're not terribly surprised," said Bill Martin, director of corporate communications for Fremont, Calif.-based SangStat, noting that the drug is not absorbed systemically and thus would more likely be effective in a mucosal disorder such as ulcerative colitis.

Patients given 200 mg per day of the anti-inflammatory peptide RDP58 showed a peak response rate of 77 percent and a 71 percent remission rate - both statistically significant - but in Crohn's disease, only 66 percent of patients treated with the same dose achieved response.

The trials for ulcerative colitis and Crohn's disease were separate but similarly designed: randomized, blinded, placebo-controlled, multicenter, 231-patient Phase II studies. RDP58 was provided as a powder to be mixed with water, and patients were instructed to drink it once each morning before meals.

Study participants got either placebo, 100 mg/day, 200 mg/day or 300 mg/day of RDP58 for 28 days. Primary endpoints were response and remission on day 28 of each study, and patients were followed for 56 days.

The dose may have been too low to affect Crohn's disease and the test period may have been too short, Martin said.

"We think we may have seen a little activity," he told BioWorld Today. Although 60 percent of patients who received 200 mg/day of RDP58 achieved a response, the effect dropped back to 48 percent in the 300-mg/day dosing arm.

"Most of the Crohn's disease studies I've seen have been eight- to 12-week periods," Martin said. "We're going to assess the value of moving forward in Crohn's." A decision will be made in "the next month or so," he said.

In the meantime, he said, "the key is how soon can we get the data finalized and wrapped up," and begin talks with the FDA about the next step. That's expected to happen in the third quarter.

"The endpoints are final, they're not going to change," Martin said. "But we have some more analysis to do."

Although related, the two disorders are not the same, Martin noted.

"Crohn's disease tends to affect a much deeper layer of the intestinal wall," he said.

Malvern, Pa.-based Centocor Inc.'s Remicade (infliximab) is approved for Crohn's disease and rheumatoid arthritis. It is in Phase III trials for ulcerative colitis. It is an anti-tumor necrosis factor therapy.

"TNF-alpha does seem to be important in each disease, but more important in Crohn's," Martin said.

In the ulcerative colitis trials, response was defined as a decrease in the Simple Clinical Colitis Activity Index (SCCAI) score of 3 or more and remission was defined as a score of 3 or less. The 127 patients who enrolled in the study entered with SCCAI scores of 4 to 9.

In the Crohn's disease trials, response was defined as a decrease in the Crohn's Disease Activity Index (CDAI) score of 70 or more and remission was defined as a score of 150 or less. The 104 patients enrolled in the study entered with CDAI scores of 220 to 400.

Late last month, SangStat ended its CEO search by appointing interim CEO Richard Murdock permanently. Jean-Jacques Bienaime, who had been CEO of SangStat for four years, left in November to become president and CEO of Genencor International Inc., of Palo Alto, Calif., and board member Murdock stepped in.

Earlier this month, a federal court in Delaware overturned a July 2002 ruling pertaining to Gengraf cyclosporine capsules for prophylaxis of organ rejection in kidney, liver and heart allogeneic transplants.

The federal court said Gengraf does not infringe on patents related to Basel, Switzerland-based Novartis AG's drug Neoral, although the decision is expected to be appealed. SangStat, which distributes Gengraf exclusively in the U.S., has a co-promotion agreement with Abbott Laboratories Inc., of Abbott Park, Ill., under which the companies share marketing expenses and profits.

In May 2000, the FDA approved Gengraf capsules, which are interchangeable with Neoral capsules. SangStat got approval for its cyclosporine in solution form, called SangCya, in 1998, and signed with Abbott for marketing the following year. (See BioWorld Today, Nov. 5, 1998, and May 11, 1999.)

Novartis was awarded $5 million in damages and sought to have Gengraf removed from the market, but the damages were assigned to Abbott. Only if the product were no longer sold would SangStat lose money - about $35 million, although the company said Gengraf has less impact on the company's earnings than Thymoglobulin, approved in 1998 for treatment of renal transplant acute rejection. Thymoglobulin sold $55.2 million last year in the U.S. and $80 million globally.