arGentis Pharmaceuticals, LLC said the US Food and Drug Administration (FDA) has granted orphan drug designation to the company's product candidate ARG201 (native type 1 bovine collagen) for the treatment of diffuse systemic sclerosis, also known as systemic scleroderma (SSc). SSc is a debilitating and fatal autoimmune disease.

Systemic sclerosis (SSc or systemic scleroderma), a type of Scleroderma, is an autoimmune disease where the immune system attacks the body's own type 1 collagen causing 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, 2003). There are approximately 80,000 SSc patients in the US with similar numbers in the European Union. No therapies are presently available to treat the underlying cause of the disease.

The use of orally administered, highly purified native bovine type 1 collagen (CI) for the treatment of SSc was pioneered by Arnold Postlethwaite, M.D., Director of the Division of Connected Tissue Disease at The University of Tennessee Health Science Center and Andrew Kang, M.D., Professor of Medicine in Rheumatology at The University of Tennessee Health Science Center. According to Dr. Postlethwaite, "One of the most widely distributed auto-antigens in SSc is type I collagen (CI), the most abundant protein in the body and a component of all tissues, organs and blood vessels involved in the disease processes of SSc. Immune tolerance is induced by orally introducing type 1 collagen, meaning that the body's immune system, over time, ceases to attack its own type 1 collagen."

ARG201 has completed an NIH-funded, 168-patient, double-blind, placebo-controlled phase II clinical trial with 13 major Rheumatology Centres participating to include Johns Hopkins University, Northwestern University Medical School, UCLA and the University of Tennessee Health Science Center. The trial included patients with the diffuse form of systemic sclerosis. These patients have cutaneous sclerosis over the limbs, trunk, and face with fibrosis of internal organs as well. In addition to the placebo group there were two prospectively defined subgroups in the phase II trial: patients who had been diagnosed for less than three years (early phase) and those diagnosed from three to ten years (late phase). Patients were treated for 12 months with follow up at 15 months. Data from the trial demonstrated a statistically and clinically significant improvement in Modified Rodnan Skin Scores (MRSS), a measure of the change in skin thickening and an FDA-mandated endpoint, at 15 months in late phase patients receiving the treatment versus the placebo group. CI was also shown to be safe and well-tolerated.

Orphan drug designation entitles arGentis Pharmaceuticals to seven years of marketing exclusivity for ARG201 upon regulatory approval, as well as the opportunity to apply for grant funding from the US government to defray costs of clinical trial expenses, tax credits for clinical research expenses and potential waiver of the FDA's application user fee. Orphan status is granted by the FDA to promote the development of new drug therapies for the treatment of diseases that affect fewer than 200,000 individuals in the United States.

"This is a very important milestone in bringing ARG201 to tens of thousands of patients with diffuse systemic sclerosis. We are moving as rapidly as possible to make this a reality," said Tom Davis, CEO, arGentis Pharmaceuticals.

Scleroderma is a disease that causes thickened skin and varying degrees of organ dysfunction resulting from small-vessel vasculopathy and immune-mediated fibrosis. The clinical manifestations of this disease are extremely heterogeneous and depend on the presence and degree of internal organ involvement. Patients may present with a spectrum of illness ranging from localized skin fibrosis only (localized scleroderma) to a systemic disorder (systemic scleroderma or systemic sclerosis) with both cutaneous and internal organ involvement. The latter is the most severe with a median patient survival of 11 years from diagnosis.

arGentis Pharmaceuticals, LLC is a specialty pharmaceutical company which seeks to in-license therapies for chronic diseases with demonstrated proof of concept for further development and commercialisation.