Alexion bags Ultomiris EU approval for paroxysmal nocturnal hemoglobinuria

Ultomiris EU approval : Alexion Pharmaceuticals has secured approval from the European Commission (EC) for its C5 complement inhibitor Ultomiris (ravulizumab) for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in adults.

The Ultomiris EU approval is for patients with PNH with hemolysis with clinical symptoms that indicate high disease activity, and also for adult patients who are clinically stable following treatment with Soliris (eculizumab) for at least the past six months.

Considered to be an ultra-rare and severe disease, PNH if left untreated, can result in a wide variety of debilitating symptoms and complications such as thrombosis, which occurs when a blood clot forms inside a blood vessel and slows or prevents the flow of blood via the circulatory system.

According to Alexion Pharmaceuticals, Ultomiris (ravulizumab) is the first and only long-acting C5 inhibitor that is administered to patients every eight weeks. The C5 complement inhibitor functions by blocking the C5 protein in the terminal complement cascade, which is a part of the immune system.

When activated in an uncontrolled manner, the terminal complement cascade, plays a role in severe ultra-rare disorders such as PNH, including atypical hemolytic uremic syndrome (aHUS), anti-aquaporin-4 (AQP4) auto-antibody-positive neuromyelitis optica spectrum disorder (NMOSD), and anti-acetylcholine receptor (AchR) antibody-positive myasthenia gravis (MG).

Alexion secures Ultomiris EU approval for paroxysmal nocturnal hemoglobinuria. Photo: courtesy of Business Wire.

Commenting on Ultomiris EU approval, Dr. Alexander Roth – Department of Hematology, West German Cancer Center at University Hospital Essen in Germany, said: “More than a decade after SOLIRIS was approved, Ultomiris provides a major step forward in the treatment of PNH.

“Now PNH patients can experience greater freedom in their lives with significantly fewer infusions per year without any compromise on efficacy or safety. This has been impressively demonstrated in the largest phase 3 program conducted in PNH so far.”

Basis of Ultomiris EU approval

The Ultomiris EU approval was driven by results from two phase 3 trials in PNH. In these late-stage trials, over 440 patients were enrolled, who were never been treated with a complement inhibitor before, or those had been stable on Soliris.

The efficacy of Ultomiris given to the patients every eight weeks was found to be non-inferior to the efficacy of Soliris administered every two weeks across all 11 primary and secondary endpoints. The safety profile of Ultomiris was identical to that of Soliris.

Additional data proved that Ultomiris delivered immediate and complete C5 inhibition that was maintained for eight weeks between doses, and that the drug eliminated breakthrough hemolysis related to incomplete C5 inhibition.

John Orloff – Executive Vice President and Head of Research & Development at Alexion Pharmaceuticals, commenting on Ultomiris EU approval, said: “We believe Ultomiris will become the new standard of care for patients with PNH by providing immediate and complete C5 inhibition, sustained throughout the eight week dosing interval, and reducing the number of infusions per year from 26 with SOLIRIS to only six or seven with Ultomiris. We are also particularly pleased by the positive data showing patients can successfully transition from SOLIRIS to Ultomiris.”

Ultomiris EU approval follows the December 2018 approval for Ultomiris (ravulizumab-cwvz) by the US Food and Drug Administration (FDA) for the same indication, and the approval from the Japanese Ministry Of Health, Labour And Welfare (MHLW) last month.