Amgen Astellas BioPharma K.K. (Headquarters, Tokyo; President and Representative Director: Steve Sugino, “Amgen Astellas”) and Astellas Pharma Inc. (Headquarters, Tokyo; President and CEO: Kenji Yasukawa, Ph.D., “Astellas”) today announced that Amgen Astellas filed an application for supplemental indication in Japan for Repatha® SC Injection 140 mg (evolocumab (recombinant), “Repatha®”) in treating hypercholesterolemic patients with statin intolerance.

Patients with hypercholesterolemia are primarily treated with HMG-CoA reductase inhibitors (statins). However, certain patients in Japan have been shown to have statin intolerance, with an inability to continue with an effective dose of statins due to muscle-related side effects. If a patient is statin intolerant, their statin dosage is decreased or discontinued, and treatment with other non-statin drugs is considered. 

“The population of hypercholesterolemic and statin-intolerant patients in Japan is currently unknown” says Koji Kajinami  M.D., Ph.D., Professor of the Department of Cardiology, Kanazawa Medical University, “however, we face a clear challenge in treating such patients who cannot continue taking statins due to muscle-related side effects. Even with statins, LDL-cholesterol (LDL-C) levels can be difficult to control in many patients. When discontinuing statin therapy, we must use other drugs to achieve similar or better LDL-C levels. There is a need for new non-statin LDL-lowering alternatives.”

The application for supplemental indication was filed on the basis of the outcomes of the Phase 3 randomized study Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-4 (GAUSS-4) enrolling statin intolerant Japanese subjects. In GAUSS-4, results were statistically significant for the co-primary endpoints of percent change in LDL-C from baseline at the mean of weeks 10 and 12, and at week 12.

Jointly developed by Amgen Astellas and Astellas, Repatha® is a human IgG2 monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver's ability to remove LDL-C, or “bad” cholesterol, from the blood. 1, 2 Repatha was approved for the indication of familial hypercholesterolemia or hypercholesterolemia (only in patients with high risk of cardiovascular events and who do not adequately respond to HMG-CoA reductase inhibitors) in January 2016 and was launched in April of the same year in Japan. Additionally, in the drug price revision in April, the premium for true clinical utility (5% premium) was applied to Repatha® on the basis of the FOURIER study results.

Currently, Repatha® carries a precaution to administer as an adjunct to statin therapy. The present application for supplemental indication was filed to provide the alternative of Repatha® monotherapy in patients who are statin-intolerant. 

Amgen Astellas and Astellas are hopeful that the application for supplemental indications will lead to the provision of new treatment alternatives for statin intolerant hypercholesterolemia patients and will contribute further to the treatment of hypercholesterolemia.