Rare Daily Staff

The U.S. Food and Drug Administration has granted marketing approval to Alexion Pharmaceuticals for its long-acting C5 complement inhibitor Ultomiris for the treatment of atypical hemolytic uremic syndrome in adult and pediatric (one month of age and older) patients.

The approval expands the uses of Ultomiris, which was first approved in January to treat paroxysmal nocturnal hemoglobinuria, a rare blood disorder.  

Atypical hemolytic uremic syndrome (aHUS) is a severe and chronic ultra-rare disease that can cause progressive damage to vital organs, predominantly the kidneys, leading to kidney failure and premature death. Ultomiris works by inhibiting the complement-mediated thrombotic microangiopathy that leads to kidney destruction.

Ultomiris is a monoclonal antibody that works to quiet the immune response. It works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. The terminal complement cascade, when activated in an uncontrolled manner, plays a role in severe ultra-rare disorders like aHUS.

“The primary approach to treatment is to prevent the body from attacking itself, through the inhibition of uncontrolled complement activation, referred to as C5 inhibition,” said Spero Cataland, professor of clinical internal medicine, Wexner Medical Center, The Ohio State University College of Medicine. “Clinical study results showed adult and pediatric patients had complete C5 inhibition following the first dose of Ultomiris. C5 inhibition was sustained over time with only six or seven infusions a year in adults—and that is important to consider for my patients.”

The FDA approval is based on data from two global, single-arm open-label studies of Ultomiris – one in adults and one in children – with aHUS. The pediatric study is ongoing and a total of 14 out of 16 children were enrolled and included in the interim analysis. In the initial 26-week treatment periods, 54 percent of adults and 71 percent (interim data) of children demonstrated complete Thrombotic Microangiopathy (TMA) Response.

Ultomiris will carry a black box warning because some patients treated with the drug experienced life-threatening meningococcal infections and sepsis.

Alexion has been looking to increase Ultomiris’ approved uses as its flagship product Soliris faces the loss of market exclusivity and increased competition. According to Wall Street analysts, Ultomiris is more convenient for patients, who need to be infused only once every eight weeks, compared to every two weeks for those taking Soliris. It is also more potent and slightly cheaper. 

Alexion is currently testing Ultomiris in other rare disorders including neuromyelitis optica spectrum disorder (NMOSD) and generalized myasthenia gravis.

Photo: Spero Cataland, professor of clinical internal medicine, Wexner Medical Center, The Ohio State University College of Medicine

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