FDA Approves Eculizumab to Treat Atypical Hemolytic Uremic Syndrome

Under its priority review program used “for an expedited six-month review of drugs that may offer major advances in treatment or that provide a treatment when no adequate therapy exists,” the FDA approved Soliris (eculizumab) to treat pediatric and adult patients with the “ultra-rare, life-threatening, genetic disease,” atypical hemolytic uremic syndrome (aHUS). The early deaths in patients with aHUS is due to “chronic uncontrolled activation of the complement system, resulting in the formation of blood clots in small blood vessels throughout the body;” thrombotic microangiopathy. Treating patients with Soliris will inhibit complement-mediated TMA by specifically targeting “uncontrolled complement activation.” Initially approved in 2007 to treat paroxysmal nocturnal hemoglobinuria, Soliris is the first approved treatment for aHUS.

Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said, “This approval underscores how an increased understanding of the biology of a disease and of how a drug interacts with that process can expedite drug development.”

In order to measure Soliris’ effectiveness, researchers evaluated the drug through two single-arm clinical trials in adult and pediatric patients with atypical hemolytic uremic syndrome. Common side effects included hypertension, diarrhea, headaches, anemia, vomiting, nausea, upper respiratory and urinary tract infections, and a decrease in white blood cells. However, upon reviewing the results, the researchers found that there was a “favorable improvement in kidney function, including elimination of the requirement for dialysis in several patients with aHUS that did not respond to plasma therapy.”

“In clinical trials, Soliris markedly decreased the TMA process, which is responsible for thrombosis, renal impairment, seizures, and angina in patients with aHUS,” said Craig B. Langman, MD, The Isaac A Abt MD Professor of Kidney Diseases, Head of Kidney Diseases, Feinberg School of Medicine, Northwestern University. “This is the first time I have seen a therapy with such a dramatic benefit, including restored kidney function. Soliris can change the course of aHUS and make a remarkable difference for patients with this life-threatening disease.”

It is important for physician to note that the new Soliris indication “is being approved with an extension of the Risk Evaluation and Mitigation Strategy (REMS)” based on its risk of life-threatening meningococcal infections.

Should a physician be interested in prescribing Soliris, he or she “must enroll in a registration program and provide a medication guide to patients who receive the drug.”

“The FDA approval of Soliris in aHUS marks the most important advance that has been made for patients and families with this disease,” said Larry Greenbaum, MD, PhD, Director of Pediatric Nephrology at Emory University and Children’s Healthcare of Atlanta.