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EU Expands Indication for AstraZeneca's C5 Protein Inhibitor Ultomiris

NEW YORK – The European Commission has approved AstraZeneca's Ultomiris (ravulizumab) as a treatment for a rare autoimmune disease in the EU, the company said Wednesday.

Ultomiris was developed by Alexion, a pharmaceutical company focused on rare diseases that AstraZeneca acquired in 2021. The drug is already approved in the EU, US, and Japan for certain adults with generalized myasthenia gravis and paroxysmal nocturnal hemoglobinuria.

European regulators have now also approved Ultomiris for adults with anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD), a rare autoimmune disease in which the body's immune system attacks healthy cells and tissues in the central nervous system. About three-quarters of people with NMOSD produce antibodies that bind to the protein aquaporin-4, inappropriately activating part of the immune system known as the complement system.

Ultomiris, an intravenously administered therapy that inhibits the C5 protein, is administered to NMOSD patients every eight weeks after an initial loading dose.

The EC approved Ultomiris based on results from a global Phase III trial, which enrolled 58 patients with a confirmed NMOSD diagnosis and a positive anti-AQP4 antibody test. In the trial, Ultomiris met the primary endpoint of time to first on-trial relapse, with no relapses observed among patients with a median treatment duration of 73 weeks. Outcomes in the Ultomiris arm were compared to an external placebo arm from a pivotal Phase III clinical trial of Soliris (eculizumab), another monoclonal antibody for NMOSD developed by Alexion. Twenty of 47 patients in the external placebo arm reported adjudicated relapses. 

According to the firm, a direct placebo comparator was not possible due to ethical reasons since there are other available and effective treatment options for NMOSD. Soliris, which is approved in the EU and US, has a shorter dosing interval than Ultomiris, at once every two weeks.

The most common adverse events in the trial testing Ultomiris were COVID-19, headache, back pain, arthralgia, and urinary tract infection, although all COVID-19 cases were considered to be unrelated to the drug, according to AstraZeneca.

Regulators in other countries including in the US and Japan are reviewing AztraZeneca's submissions seeking approval for Ultomiris in NMOSD.