Stepping forward in scleroderma

NORWOOD, Mass.—Corbus Pharmaceuticals Holdings Inc. is gearing up to advance its lead drug candidate, Resunab, thanks to clearance of its Investigational New Drug (IND) application by the U.S. Food and Drug Administration. Corbus announced recently that its IND application is now open, and it is now moving forward to begin a Phase 2 clinical study of Resunab for the treatment of diffuse cutaneous systemic sclerosis (scleroderma).

The Phase 2 trial will be a double-blind, randomized, placebo-controlled study with multiple doses, and will seek to enroll roughly 36 scleroderma patients that will receive daily treatment for three months. An 18-month completion time is expected. The study will evaluate the safety and tolerability of Resunab, as well as its potential impact on clinical outcomes as measured by the combined response index for systemic sclerosis, or CRISS score. The study will also be investigating a number of secondary endpoints to determine any changes in patients' inflammatory status. Corbus expects to begin the study in the second quarter of this year, with plans to submit a Phase 2 protocol under this open IND for the treatment of cystic fibrosis in the same quarter.

“This IND clearance enables us to proceed with our Phase 2 study in scleroderma and represents a major step forward in our clinical development strategy for Resunab,” Dr. Barbara White, chief medical officer of Corbus, commented in a statement. “We look forward to working with our clinical investigators to advance Resunab in this Phase 2 study aimed at establishing safety in this patient population and modifying the outcome of this disease. Based on its novel mechanism of activating the inflammatory resolution pathway, Resunab has the potential to become an important therapy for scleroderma patients as well as for potentially other diseases in which chronic inflammation and fibrosis are present.”

Resunab is a novel, oral specialized pro-resolving mediator drug that binds to the CB2 receptor on immune cells, triggering a process known as inflammatory resolution, which essentially “turns off” chronic inflammation. The drug has shown a favorable safety profile in preclinical and Phase 1 clinical studies, with encouraging potency in preclinical models of inflammation and fibrosis.

As noted on Corbus' website, Resunab has served to “reduce immune-mediated inflammation and tissue injury by acting on and influencing cellular immunity (inducing apoptosis of T-lymphocytes), inhibiting leukocyte migration, reducing cytokines secretion (IL-1β, IL-6 and IL-8), inhibiting matrix metalloproteinase production (MMP-1, -3, -9), reducing pro-inflammatory eicosanoid levels (PGE2, LTB4) and increasing resolving eicosanoid production (PGJ2, LXA4).”

“I am looking forward to investigating Resunab’s potential to address such an important unmet medical need for the estimated 50,000 adults with scleroderma in the U.S. who could benefit from a potentially safe and effective treatment option for their severe, progressive and currently untreatable fibrosis,” said Dr. Robert Spiera, director of the Vasculitis and Scleroderma Program at the Hospital for Special Surgery in New York City. Spiera will be lead investigator for this study.

Scleroderma is a chronic connective tissue disease that is generally classified as an autoimmune rheumatic disease with an unclear etiology. The disease presents in two forms, limited and diffuse; the diffuse cutaneous systemic form is the most severe and affects approximately 50,000 individuals in the United States. Women represent about 80 percent of scleroderma sufferers, and a mid-life onset is most typical. Within this more severe form of the disease, the immune system attacks and damages the skin, which results in the skin thickening rapidly over a large area. This can eventually involve other parts of the body, including the esophagus, gastrointestinal tract, lungs, kidneys, heart and other internal organs, as well as blood vessels, muscles and joints. Pulmonary fibrosis is the leading cause of death related to this disease, and there are no existing effective therapies.

TGF-beta (transforming growth factor beta), a pro-inflammatory and pro-fibrotic cytokine, has been tagged as a key player in the progression of this disease. This protein controls proliferation, differentiation and other functions within cells, and is linked to cancer, asthma, lung fibrosis, heart disease, multiple sclerosis and diabetes, among other diseases. Among the cells that secrete TGF-beta are macrophages, one key type of white blood cell in the immune system; inflammatory stimuli are one of many factors that can trigger the release of TGF-beta.