Systemic scleroderma is a systemic autoimmune disease characterized by vasculopathy and fibrosis that hardens the skin and many organs, and the intractable disease designated by the government based on the ” Act on Medical Care for Patients with Intractable Diseases” (Designated intractable diseases No 51). Its etiology is unknown, and there is no curative treatment based on the pathogenesis. Fibrosis associated with systemic scleroderma causes clinical manifestations such as skin hardening and interstitial lung disease. It is estimated that there are more than 30,000 patients in Japan, and 70% of their deaths are due to this disease, and of these, more than 30% are due to interstitial lung disease. Even when interstitial lung disease is not the direct cause of death, it is known that in some patients, it severely restricts daily life in some patients due to severely impaired respiratory function.

Current Treatments and Challenges

Traditionally, the first-line treatment for interstitial lung disease associated with systemic scleroderma has been a combination of steroids and immunosuppressive agents, but their efficacy has been extremely limited. Recently, nintedanib, a drug that suppresses fibrosis, has been covered by insurance. However, its effectiveness is limited to suppressing the progression of interstitial lung disease and cannot restore fibrosis to normal tissue. It is a challenge that no treatment is not established for this disease.

Characteristics of Our Solution

Systemic scleroderma involves inflammation, vascular injury, and fibrosis as its three major clinical conditions, and RS5614 ameliorates these conditions, especially lung injury (fibrosis and inflammation) and has protective effects on lung epithelia, suggesting that RS5614 may ameliorate interstitial lung disease associated with systemic scleroderma.

In collaboration with Tohoku University, we evaluated the effects of RS5614 in a non-clinical pharmacological study using a mouse model of systemic scleroderma that is widely recognized as fibrosis model in skin and lung. The results showed that RS5614 markedly suppressed lung fibrosis in this model, and the higher the dose of RS5614, the greater the effect. RS5614 was more effective than the active control drug nintedanib. These results suggest that RS5614 is effective in the treatment of interstitial lung disease associated with systemic scleroderma, and that its efficacy is superior to that of the existing drug nintedanib.

An exploratory phase II study (investigator-initiated clinical trial) to confirm the efficacy and safety of RS5614 in interstitial lung disease associated with systemic scleroderma has being conducted at several medical institutions in Japan, including Tohoku University Hospital.