Alexion Receives EU Approval for Ultomiris for aHUS

The European Commission has granted marketing approval to Alexion Pharmaceuticals for its long-acting C5 complement inhibitor Ultomiris for the treatment of atypical hemolytic uremic syndrome.

The approval of Ultomiris is for use in adult and pediatric patients with a body weight of 10 kg or above who are complement inhibitor treatment-naïve or have received and are responsive to Soliris (eculizumab) for at least three months.

The approval expands the uses of Ultomiris, which was first approved to treat paroxysmal nocturnal hemoglibinuria, 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 is a monoclonal antibody that 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, causes the thrombotic microangiopathy that leads to kidney destruction and plays a role in severe ultra-rare disorders like aHUS.

“The consequences of aHUS are severe and potentially life-threatening, creating significant challenges and uncertainty for patients and their families. The goal of aHUS treatment is to prevent the body from attacking itself through the inhibition of uncontrolled C5 complement activation – a part of the body’s immune system,” said Hermann Haller, professor in the Clinic for Nephrology, University Hannover, Germany. “Clinical study results showed that both adults and children with aHUS had immediate and complete C5 inhibition following the first dose of Ultomiris sustained for up to eight weeks. In addition to having demonstrated clinically meaningful benefits in people with aHUS, Ultomiris provides greater freedom with significantly fewer infusions per year.”

The European Commission approval is based on data from two global, single-arm open-label studies of Ultomiris – one in adults and one in children—with aHUS. Both studies are ongoing. A total of 18 out of 21 complement inhibitor treatment-naïve children and 56 out of 58 complement inhibitor treatment-naïve adults were enrolled and included in the interim analysis. In the initial 26-week treatment periods, 54 percent of adults and 77.8 percent (interim data) of children demonstrated complete Thrombotic Microangiopathy (TMA) response.

Although serious meningococcal infections have occurred in patients treated with Ultomiris, no meningococcal infections occurred in the 89 patients receiving treatment in the aHUS study. To minimize the risk for patients, specific risk-mitigation plans, including a Risk Management Plan, have been established.

Ultomiris was approved to treat aHUS in adults and children in the United States in October 2019, and is currently under review by Japanese regulators.  It is also approved for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) in the U.S and Japan, and in the EU as a treatment for adult patients with PNH with hemolysis with clinical symptoms indicative of high disease activity and also for adult patients who are clinically stable after having been treated with eculizumab for at least the past six months.

“Today’s marketing authorization marks an important step in our efforts to establish Ultomiris as the new standard of care for the aHUS patient community,” said John Orloff, execute vice president and head of R&D at Alexion.

Alexion has been looking to increase the uses of Ultomiris as its flagship product Soliris faces the loss of market exclusivity and increased competition. 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, at least in the United States.

Photo: John Orloff, execute vice president and head of R&D at Alexion

Author: Rare Daily Staff