By Lisa Seachrist
Connetics Corp. initiated a pivotal Phase II/III study of ConXn (recombinant human relaxin-H2) as a therapy for scleroderma.
The trial will test two dosages of ConXn against placebo in 200 patients with diffuse scleroderma, a life-threatening connective tissue disease. The study will serve as the linchpin of a biologics license application, which Palo Alto, Calif.-based Connetics hopes to complete in early 2001.
"There is a huge need for a drug to treat this disease," said John Higgins, chief financial officer at Connetics. "There really isn't much that works against this disease. The data from our Phase II trial showed that ConXn actually reversed the disease."
Scleroderma is characterized by thickening of the skin as a result of excessive production of collagen. The disease afflicts 300,000 people in the U.S., 80 percent of them women.
As collagen invades the skin, it causes it to harden. Most patients have a localized version of the disease that affects the hands or extremities. In diffuse scleroderma, collagen invades not only the skin, but internal organs as well. Fifty to 70 percent of patients diagnosed with diffuse scleroderma die from pulmonary fibrosis or cardiac fibrosis within five years of diagnosis.
Relaxin is a naturally occurring protein hormone comprised of 52 amino acids. It is associated with pregnancy in that it helps prepare a woman by relaxing the ligaments in the pelvic area.
Relaxin - and ConXn - work by decreasing the amount of collagen produced and increasing the amount of collagenase - an enzyme that breaks down collagen. In effect, the naturally occurring agent and ConXn are antifibrotic agents.
The antifibrotic character of relaxin was first recognized in 1958, when a study of purified porcine relaxin published in the Journal of the American Medical Association concluded relaxin had a positive effect on scleroderma. However, porcine relaxin proved too difficult to reliably purify and it was removed from the market.
Connetics licensed the human recombinant version of relaxin from Genentech Inc., of South San Francisco, in 1993 as one of its founding products.
The pivotal ConXn trial will randomize 200 patients to either a 25 microgram per kilogram per day dose of ConXn, a 10 microgram per kilogram per day dose, or a placebo. ConXn will be delivered via a small portable insulin pump.
Patients will be treated for six months, after which investigators will measure ConXn's effect on skin fibrosis (hardening), vital organ function and global assessment scores by both patients and physicians. The primary endpoint for the trial is an improvement in the Modified Rodnan Skin Score, a measurement of skin thickness at 17 areas of the body.
Trial Expected To Finish In Second Half Of 2000
Higgins pointed out that improvement is a high bar to set for success because scleroderma is a progressive disease and the best that is often expected in such situations is to stop progression. However, Phase II studies of the drug showed the 25 microgram dose provided a statistically significant improvement in disease symptoms.
Higgins said the company expects the trial will take six months to fully enroll and will be completed sometime in second half of 2000.
Connetics recently announced that it had signed a $40 million deal with Medeva plc, of London, to develop and market ConXn in Europe. (See BioWorld Today, Jan. 13, 1999, p. 1).
In April 1998, Connetics signed a $14 million deal with Suntory Ltd., of Osaka, Japan, to develop and sell ConXn for scleroderma in Japan.
Connetics stock (NASDAQ:CNCT) closed Tuesday at $7.875, up 50 cents.