By Karen Pihl-Carey

Recombinant human relaxin achieved statistical significance in its primary endpoint in a Phase II trial, poising Connetics Corp. for a biologics license application filing in 2001.

The Palo Alto, Calif.-based company needs only to wait for results from its pivotal Phase II/III trial. If those results support the Phase II findings, the company will move forward with the BLA, said Greg Vontz, executive vice president and chief commercial officer at Connetics.

"Probably, the trial will close out in late fall this year. We hope to see data in the fourth quarter. So we're close to the big event," Vontz told BioWorld Today.

The Phase II results were published Tuesday in the Annals of Internal Medicine. The trial involved 68 patients with stable, moderate to severe diffuse scleroderma of less than five years of duration. They received either a placebo or doses of 25 micrograms per kilogram or 100 m5/kg of relaxin, which was administered daily by continuous subcutaneous infusion over 24 weeks. The primary endpoint was the improvement of skin scores, which were measured with the Modified Rodnan Skin Score.

"Basically, it gives a measurement of the patient's thickness of the skin," Vontz said. "There is a very direct correlation between skin scores and quality of life."

Patients treated with the 25 m5/kg dose demonstrated statistically significant improvement in skin score at four weeks (p=.021), 12 weeks (p<.001) and 24 weeks (p=.040), compared with the placebo group. Patients on the 100 m5/kg dose did not show a statistically significant improvement, which is consistent with the in vitro dose response, the company said.

"Not only did we have a positive primary endpoint in our Phase II trial," Vontz said, "but we also had very positive trends in terms of lung function and oral aperture."

The trial also showed positive trends in other secondary parameters, such as hand extension, and measures of disability parameters, such as eating, gripping, reaching and personal hygiene. Adverse events included menometrorrhagia, reversible anemia and site irritation and local infection.

The pivotal scleroderma trial began in February 1999 and just recently completed enrollment with 239 patients. The company is conducting a six-month follow-up for the patients before releasing any results. The design of the trial was identical to the Phase II trial, except it involved more patients. (See BioWorld Today, Feb. 24, 1999, p. 1.)

Connetics holds exclusive rights to relaxin in the U.S. and plans to sell and market the product on its own, Vontz said.

Scleroderma affects up to 100,000 Americans, most of them women of childbearing age. Fibrosis - or scarring - of skin and internal organs causes disfigurement and disability, with 50 percent of patients surviving as long as 10 years. There are no effective disease-modifying treatments.

Relaxin, formerly called ConXn, is a naturally occurring hormone that promotes vasodilation and angiogenesis and inhibits fibrosis. Aside from the pivotal trial for scleroderma, it also is in a Phase I/II trial to treat infertility. Based on preclinical data, the company expects to soon begin a clinical trial with relaxin to treat peripheral arterial disease and other diseases of ischemia and fibrosis.

Connetics' stock (NASDAQ:CNCT) closed Tuesday at $10, down 31.25 cents.