June 30, 2008
Phase II Results for Low-Dose Oral Immune Tolerance Therapy (ARG201) in Systemic Scleroderma Published
arGentis Pharmaceuticals, LLC announced today that the Phase II results using highly purified type 1 bovine collagen orally (now known as ARG201) in the treatment of diffuse cutaneous systemic sclerosis (scleroderma - SSc) have been published in the June issue of Arthritis & Rheumatism, a major peer-reviewed rheumatology research journal. Systemic sclerosis is an autoimmune disease causing widespread fibrosis of the skin and internal organs. ARG201 is an immunotherapy that induces low dose oral immune tolerance in SSc patients causing downregulation of the body's autoimmune response. There are no approved treatments for the underlying cause of SSc, which has a median survival of eleven years (Mayes 2004).
The article entitled, "A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Oral Type I Collagen Treatment in Patients With Diffuse Cutaneous Systemic Sclerosis," reviews the results of the 168-patient, twelve center trial in which patients were administered a precise dose of highly purified type 1 collagen or placebo for 12 months with follow up at 15 months. Two prospectively subpopulations, Early Phase SSc patients (diagnosed for less than or equal to 3 years) and Late Phase SSc patients (diagnosed from 3 to 10 years) were included in the trial due to differences in immunologic function of the two groups. The differences were borne out in the trial results. Late Phase patients had a statistically and clinically significant decrease from baseline in modified-Rodnan Skin Scores (-7.9 units) in the collagen treated patients versus the placebo group (-2.9 units). There was no difference in skin scores in Early Phase patients; although subsequent analysis demonstrated that patients who have been diagnosed as early as 1.75 years diagnosis may benefit from type 1 collagen therapy. The trial also demonstrated a high correlation between Late Phase patients who had significant changes in skin scores and that of other clinical outcomes. There were no adverse events in the trial attributed to the therapy.
Additionally, whether patients had at least 25% improvement in MRSS depended on whether they were Early or Late Phase patients at 12 months (p=0.014) and 15 months (p=0.031). A statistically significant upregulation of IL-10 (p=0.01), a marker for tolerance induction and a potent antifibrotic cytokine, was also seen in treated Late Phase SSc patients at 12 and 15 months.
"This trial delineated both clinically and immunologically the differences between Early Phase and Late Phase diffuse SSc patients," said Arnold E. Postlethwaite, principal investigator. "The reduction in skin scores among the Late Phase patients also demonstrates clinically meaningful improvement for the first time in a large, randomized trial in systemic sclerosis."
ARG201 has been granted orphan status by the U.S. Food and Drug Administration. Phase III trials will begin in the first half of 2009.
About Systemic Sclerosis
Systemic sclerosis (SSc or systemic scleroderma), a type of Scleroderma, is an autoimmune disease causing widespread fibrosis of the skin, lungs and other organs. As SSc progresses, patients suffer increasing difficulties with digestion, breathing, joint pain and often develop pulmonary hypertension. Median survival from diagnosis is eleven years (Mayes, 2004). There are approximately 80,000 SSc patients in the U.S. with similar numbers in the European Union. No therapies are presently available to treat the underlying cause of the disease.
arGentis Pharmaceuticals, LLC is a diversified specialty biopharmaceutical company seeking to license and commercialize therapies with demonstrated proof of concept for chronic diseases. Our pipeline consists of mid- and late-stage platform technologies in both autoimmunity and ophthalmology. ARG201, the company's lead compound for the treatment of systemic sclerosis, will enter Phase III trials in 2009. The ophthalmology pipeline includes three therapies for dry eye syndrome which are uniquely applied to the outer upper and lower eyelids for transdermal delivery to the affected glands.