By Randall Osborne

West Coast Editor

SAN FRANCISCO - As buoyant attendees of the 18th annual Chase H&Q Healthcare Conference surged into the streets here for a lunch break, officers of Genzyme Transgenics Inc. gathered in an upper-floor hotel conference room to discuss the company's latest good news: positive data from a Phase III study of its recombinant human antithrombin III (rhATIII).

"Biotech has come back with a bang," said Suzanne Groet, vice president and general manager of ATIII LLC, the joint venture established by Genzyme Transgenics, of Framingham, Mass., and Genzyme General, of Cambridge, Mass., to develop the product. (See BioWorld Today, May 14, 1998, p. 1.)

That "bang" is partly evident in the stronger performance of industry stocks, but another aspect of biotechnology's resurgence of rhATIII, the first transgenic candidate to advance with favorable data in Phase III trials, Groet said. Details were disclosed as part of a presentation at the conference Monday.

The drug is designed to restore sensitivity to the anticoagulant heparin, in patients who are resistant and who undergo elective heart surgery that requires cardiopulmonary bypass (CPB). Heparin works with rhATIII to block the clotting that can occur when blood comes into contact with the foreign surface of the CPB circuit on the heart-lung machine.

ATIII is a naturally occurring blood protein that helps control the body's normal clotting mechanisms. The recombinant drug showed statistically significant results in meeting the Phase III trial's primary endpoint, which was reduction in the use of fresh-frozen plasma.

Results showed that, in heparin-resistant patients, 21 percent, or six out of 28 patients in the rhATIII-treated group, required fresh-frozen plasma to manage their resistance, compared to 92 percent, or 22 out of 24 patients, in the placebo group.

The double-blind, randomized, placebo-controlled study evaluated 52 patients in six medical centers in Germany and the United Kingdom. Another, identical Phase III study is under way.

"It's two-thirds completed, and the expectation is patient enrollment will be finished in the first quarter [of 2000]," Groet said, with first data likely in another year or so.

The drug also achieved statistical significance in two of three secondary endpoints: maintenance of normal ATIII levels, and changes in two biochemical markers of coagulation.

James Streisand, director of medical affairs for Genzyme Transgenics, said a single dose of rhATIII "maintained 100 percent or greater than normal levels over the course of the bypass, so you don't need to run an infusion. That was important."

The relevance of the coagulation markers is "a little more complicated," Streisand said, noting that it could have meaning in cases where post-CPB patients develop a condition sometimes known as "pump head," characterized by depression, low appetite and cognitive deficits.

"We're not saying that by inhibiting some of these coagulation factors that we can necessarily show pump head will decline, but there's a possibility for that," Streisand said.

Although not life-threatening, the condition "is still something that can limit the functionality of the patient," he said. "We didn't power our studies for that, but it would be interesting to look at."

Groet said rhATIII may also help maintain hemostasis, by keeping normal coagulation parameters over the course of the bypass, but Streisand said that, too, needs to be explored further.

No other company is developing a recombinant version of ATIII, but plasma-derived ATIII already is on the market, Groet said, adding that it's being tested in sepsis by Centeon, a joint venture between the now-merged Rhone-Poulenc Rorer Inc. and Hoechst AG, which are pooling the resources of their respective subsidiaries: Behringwerke AG, of Marburg, Germany, and Armour Pharmaceutical Co., of Collegeville, Pa. (See BioWorld Today, Feb. 27, 1996, p. 1.)

Genzyme Transgenics also said Monday that the company signed a deal with Alexion Pharmaceuticals Inc., of New Haven, Conn., to produce a recombinant protein using the former's transgenic manufacturing system. The firms could enter into supply agreements for clinical and commercial production, but detailed terms were not disclosed.

Genzyme Transgenics' stock (NASDAQ:GZTC) closed Monday at $16.125, up $2.187, and Genzyme General's shares (NASDAQ:GENZ) ended the day at $48.875, up 93.7 cents. Alexion's stock (NASDAQ:ALXN) closed at $33.125, up 12.5 cents.

In other news at the H&Q conference:

Amylin Pharmaceuticals Inc., of San Diego, said results of additional analyses from a Phase II study show that AC2993 (synthetic exendin-4) suppressed the post-meal rise in triglyceride concentrations reducing the cardiovascular risk factor in people with Type 2 diabetes.

Incyte Pharmaceuticals Inc., of Palo Alto, Calif., and Bayer Corp., of Berkeley, Calif., entered into an agreement whereby Incyte will provide Bayer with access to Incyte's LifeSeq Gold database for therapeutic protein discovery. Bayer will have access to Incyte's patent portfolio, and Incyte could receive future milestone payments and royalties on sales of products developed with Incyte technology and information. Financial terms were not disclosed.

Inflazyme Pharmaceuticals Ltd., of Vancouver, British Columbia, said it identified a new series of potent, orally bioavailable inhibitors of the enzyme phosphodiesterase-4, which appear to be without the potential for emesis, or vomiting. A lead molecule of the series, IPL4088, also has demonstrated efficacy in in vivo models of asthma and inflammatory bowel disease.