EC Approves New Formulation of Alexion’s Ultomiris for Treatment of PNH and aHUS

Rare Daily Staff

The European Commission has approved the new 100 mg/mL intravenous formulation of Alexion Pharmaceuticals Ultomiris for the treatment of two ultra-rare diseases—paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.

Paroxysmal nocturnal hemoglobinuria (PNH) is a blood disorder characterized by complement-mediated destruction of the red blood cells that can cause a wide range of debilitating symptoms and complications, including thrombosis, which can occur throughout the body, and result in organ damage and premature death. Atypical hemolytic uremic syndrome (aHUS) can cause progressive injury to vital organs, primarily the kidneys, via damage to the walls of blood vessels and blood clots. Affecting both adults and children, aHUS patients can present in critical condition, often requiring supportive care, including dialysis, in an intensive care unit. The prognosis of both aHUS and PNH can be poor in many cases, so a timely and accurate diagnosis—in addition to appropriate treatment—is critical to improving patient outcomes.

Ultomiris is the first and only long-acting C5 inhibitor administered to patients every eight weeks or every four weeks for pediatric patients less than 20 kg. Ultomiris 100 mg/mL is an improvement in the treatment experience for patients with aHUS and PNH by reducing average annual infusion times by approximately 60 percent compared to Ultomiris 10 mg/mL, while delivering comparable safety and efficacy. With Ultomiris 100 mg/mL, most patients will spend six hours or less a year receiving treatment.

“Ultomiris has already provided patients with greater flexibility and this new formulation is another step forward in reducing the overall treatment burden,” said Professor Alexander Röth, Department of Hematology and Stem Cell Transplantation, University Hospital Essen, Essen, Germany. “With this new formulation, patients will experience comparable safety and efficacy to the original formulation while spending significantly less time per year receiving treatment, which has the potential to make a meaningful difference in their lives.”

The European Commission approval is based on a comprehensive chemistry, manufacturing and control submission and a supplementary clinical data set showing that the safety, pharmacokinetics and immunogenicity following administration of Ultomiris 10 mg/mL and Ultomiris 100 mg/mL were comparable. Similarly, the data set showed no relevant changes in the efficacy measure of mean lactate dehydrogenase (LDH) levels across the two formulations. The new proposed formulation requires an infusion time of 0.4 to 1.3 hours (25 to 75 minutes) depending on body weight, reducing the infusion time by approximately 60 percent compared with the currently available 10 mg/mL IV formulation, which ranges from 1.3 to 3.3 hours (77 to 194 minutes) depending on body weight.

“The European Commission’s approval of Ultomiris in this new formulation will provide a meaningful benefit to patients’ quality of life,” said John Orloff, executive vice president and head of Research & Development at Alexion.

The U.S. food and Drug Administration approved Ultomiris 100 mg/mL in October 2020, and a regulatory filing is under review in Japan.

Alexion also plans to submit regulatory filings in the U.S. and EU in the third quarter of 2021 for an Ultomiris subcutaneous formulation and device combination for PNH and aHUS that can be self-administered at home, pending completion of the ongoing phase 3 study and collection of 12-month safety data. In addition, the company has seven phase 3 programs that are ongoing or planned that may expand its use for the treatment for rare diseases across hematology, nephrology, neurology, and for the treatment of severe COVID-19.

Photo: John Orloff, executive vice president and head of Research & Development at Alexion