RARE Daily

Japanese Regulators Approve Alexion’s Ultomiris for Ultra-Rare Autoimmune Condition

September 29, 2020

Rare Daily Staff

Japan’s Ministry of Health, Labour and Welfare approved Alexion Pharmaceuticals’ Ultomiris for adults and children living with atypical hemolytic uremic syndrome, an ultra-rare autoimmune disorder.

Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease that can cause progressive injury to vital organs, primarily the kidneys, via damage to the walls of blood vessels and blood clots. aHUS occurs when the complement system—a part of the body’s immune system—over-responds, leading the body to attack its own healthy cells. Timely and accurate diagnosis—in addition to treatment—is critical to improving patient outcomes. Available tests can help distinguish aHUS from other hemolytic diseases with similar symptoms.

Ultomiris is the first and only long-acting C5 complement inhibitor. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. Ultomiris is administered intravenously every eight weeks or every four weeks for pediatric patients less than 20 kg, following a loading dose. Ultomiris is approved in Japan as a treatment for adults with paroxysmal nocturnal hemoglobinuria (PNH).

The approval is based on data from two ongoing, global, single-arm open-label studies of Ultomiris – one in adults and one in children. 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.

Efficacy evaluation of Complete TMA Response was defined by normalization of hematologic parameters (platelet count and LDH) and improved kidney function. In the initial 26-week treatment periods, 54 percent of adults and 77.8 percent (interim data) of children demonstrated Complete TMA Response. Treatment with Ultomiris resulted in normalization of platelet count in 84 percent of adults and 94 percent of children, normalization of LDH (marker of hemolysis) in 77 percent of adults and 90 percent of children, and improved kidney function in 59 percent of adults and 83 percent (interim data) of children (for patients on dialysis at enrollment, baseline was established after they had come off dialysis).

In the 52-week follow-up period, 4 additional adult patients and 3 pediatric patients had a Complete TMA Response that was confirmed after the 26-week Initial Evaluation Period resulting in an overall Complete TMA Response of 61 percent in adults and 94 percent in children (interim data). A second cohort of 10 pediatric patients who were being treated with Alexion’s older C5 inhibitor Soliris were included in the pediatric study, demonstrating that switching to Ultomiris maintained disease control as evidenced by stable hematologic and renal parameters, with no apparent impact on safety.

The most frequently observed adverse reactions reported in these studies were upper respiratory tract infection, diarrhea, nausea, fatigue, headache, nasopharyngitis, and pyrexia. Serious meningococcal infections have occurred in patients treated with Ultomiris, however in aHUS studies, no meningococcal infections occurred in the 89 patients receiving treatment with Ultomiris. To minimize the risk for patients, specific risk-mitigation plans, including a Risk Management Plan, have been established for Ultomiris.

“Ultomiris extended dosing interval offers patients more flexibility and time to focus on living their lives beyond their disease while also reducing the burden on healthcare systems, hospitals and providers, which are all under a tremendous amount of stress in the current environment,” said John Orloff, executive vice president and head of research & development at Alexion.

Photo: John Orloff, executive vice president and head of research & development at Alexion


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