By Frances Bishopp
Connetics Corp., which currently has four products in clinical trials, reported positive results for ConXn (recombinant human relaxin H2) in Phase II studies for scleroderma.
Connetics, of Palo Alto, Calif., said these data represent the first controlled clinical study to show positive results in the treatment of scleroderma, a life-threatening connective tissue disorder for which there is currently no treatment.
Scleroderma is a result of excessive production of collagen. The disease afflicts approximately 300,000 patients in the U.S. alone, 80 percent of whom are women.
In its most severe form (which affects some 60,000 patients) the disease results in hardening of the skin and internal organs. A is fatal in 50 to 70 percent of cases within five years.
Relaxin is a naturally occurring protein hormone associated with pregnancy, explained Scott Harkonen, senior vice president of product development and operations at Connetics. It helps to prepare a woman for pregnancy by relaxing the ligaments in the pelvic area.
Relaxin decreases the amount of collagen production and increases the collagenase, an enzyme that degrades collagen, Harkonen said. "Because of those effects on collagen," he said, "we've been developing relaxin as an antifibrotic agent, and scleroderma is the quintessential disease of excess fibrosis."
The double-blind, placebo-controlled study involved 64 patients randomized into one of two treatment groups 25 or 100 micrograms per kilogram per day, or placebo. All the patients had severe systemic scleroderma for at least one year, which included involvement of the internal organs.
Patients received a subcutaneous continuous infusion of the drug via a small, portable insulin pump for 24 weeks.
A primary endpoint for the trial was skin hardening and secondary endpoints were lung function and patient and physician global activity assessment or functional score.
In the group receiving a dose of 25 micrograms per kilogram per day, statistical significance was found in skin score improvement, Harkonen said, with a 31 percent reduction in skin scores. Positive trends were seen in all other parameters.
"It was a very consistent effect with all measures of disease activity improving in the low-dose group," Harkonen said. The higher dose, however, had no effect on the treatment group compared to placebo.
Connetics, formerly Connective Therapeutics Inc., licensed ConXn from Genentech Corp., of South San Francisco, in 1993 as one of Connetics' founding products.
Harkonen said a porcine version was available in the U.S. in the 1950s and a study on the hormone as therapy for scleroderma was published in The Journal of the American Medical Association in 1958 concluded it worked.
"The problem was trying to get reproducibly pure protein," Harkonen said, who added the product was eventually withdrawn. It wasn't until the recombinant version became available through Genentech that development continued.
In addition to ConXn, Connetics has a Phase III trial of gamma interferon for atopic dermatitis and a Phase II trial for keloids, a Phase III trial for betamethasone mousse for scalp psoriasis, and a Phase I/II trial for a vaccine for multiple sclerosis.
Connetics' stock (NASDAQ:CNCT) closed Thursday at $7.25, up $0.75. *