Bayer HealthCare recently announced the launch of a new clinical trial, the RISE-SSc study, a randomized, double-blind, placebo-controlled Phase II study to investigate the efficacy and safety of riociguat against placebo in patients with diffuse cutaneous systemic sclerosis (dcSSc), the most severe form of systemic sclerosis (SSc). Both Bayer and Merck & Co., Inc., known as MSD outside of the U.S. and Canada, established a strategic collaboration in the field of modulation of soluble guanylate cyclase (sGC) for the development of riociguat in cutaneous systemic sclerosis.

Systemic sclerosis (SSc) is a clinically heterogeneous disorder affecting the connective tissue of the skin, as well as the wall of the blood vessels and internal organs, such as the gastrointestinal tract, lungs, heart, and kidneys. The condition affects between 70 and 400 people per million. In SSc, immune responses are uncontrolled, causing chronic inflammation and concomitant changes in the endothelial cells, leading to the narrowing of the blood vessels. This narrowing causes tissue damage, circulation problems, and high blood pressure. Tissue fibrosis, i.e., the overproduction of collagen and thus excessive formation of connective tissue, contributes significantly to the high morbidity and mortality rates observed in SSc.

SSc can be divided in two main forms according to the extent of skin involvement, i.e. diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc). Both are associated with the involvement of internal organs. However, patients with dcSSc are at a higher risk for organ malfunction. After diagnosis, 15-20% of patients die in the first 5 years. Diffuse cutaneous SSc (dcSSc) affects subjects between 40 and 50 years old and is characterized by vasculopathy and progressive fibrosis of the skin and internal organs, and may lead to death. Both the standard and experimental therapies for dcSSc consist of drugs with immune-suppressive and/or anti-inflammatory effects. For patients with SSc, 35-40% have the diffuse cutaneous form, which is the most lethal rheumatic form of the disease.

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For the RISE-SSc study (Riociguat Safety and Efficacy in patients with diffuse cutaneous Systemic Sclerosis [dcSSc]) 130 patients will be recruited from more than 60 locations in 15 countries. In the study, the researchers will assess if treatment with riociguat for dcSSc over 52 weeks performs better than a placebo. The drug riociguat is a soluble guanylate cyclase (sGC) activator approved under the name Adempas® from Bayer as an oral treatment to target a crucial molecular mechanism essential for the development of pulmonary hypertension (PH). During the study, the researchers will evaluate the outcomes of the effect of riociguat on fibrosis of the skin and the lung, as well as for circulation problems like digital ulcers.

Until now there has been no available therapy able to stop or delay the damage due to the fibrotic process in patients with dcSSc. Both the European Commission and the FDA, in July 2014, granted orphan drug status for riociguat as an oral investigational drug in SSc.