The U.S. Food and Drug Adminstration (FDA) has approved Ultomiris (ravulizumab-cwvz) to treat adults and children (> 1 month of age) with atypical hemolytic uremic syndrome (aHUS).
aHUS is an ultra-rare disease, characterized by inflammation and the formation of blood clots in small blood vessels (thrombotic microangiopathy [TMA]) mediated by chronic, uncontrolled activation of the complement system. If left untreated, significant proportions of adults (56%) and children (29%) will progress to end-stage renal disease (ESRD) or die, if left untreated.
Ultomiris is a long-acting C5 complement inhibitor that is administered intravenously every 8weeks or every 84 weeks for pediatric patients less than 20 kg, following a loading dose. The drug is also approved to treat paroxysmal nocturnal hemoglobinuria (PNH).
The developers of Ultomiris, Alexion Pharmaceuticals, also developed Soliris (eculizumab), a shorter acting complement inhibitor that is also approved to treat aHUS, PHS, myasthenia gravis, and neuromyelitis optica spectrum disorder. It requires weekly or bimonthly infusion.
The approval of Ultomiris is based on two single-arm open-label studies – one in adults and one in children. Treatment with Ultomiris resulted in reduced thrombocytopenia in 84% of adults and 93% of children, reduced hemolysis in 77% of adults and 86% of children, and improved kidney function in 59% of adults and 79% (interim data) of children.
The most frequently observed adverse reactions were upper respiratory tract infection, diarrhea, nausea, vomiting, headache, hypertension and pyrexia. Serious meningococcal infections have occurred in patients treated with Ultomiris and specific risk-mitigation plans, including a REMS, have been established for the drug