Ultomiris recommended for approval in Europe to treat NMOSD adults
CHMP offers positive opinion for its use in those with anti-AQP4 antibodies
A European Medicines Agency (EMA) committee has recommended that Ultomiris (ravulizumab) be approved to treat adults with neuromyelitis optica spectrum disorder (NMOSD) who are positive for antibodies against aquaporin-4 (AQP4).
The recommendation, from the EMA’s Committee for Medicinal Products for Human Use (CHMP), will now be reviewed by the European Commission (EC), which has final say on approvals for therapies in the European Union. The EC usually abides by CHMP recommendations, though it is not required to do so.
“Today’s positive opinion advances our commitment to transform outcomes for patients with rare neurological diseases and reflects the exceptional efficacy of [Ultomiris] in reducing the risk of life-altering relapses in NMOSD,” Marc Dunoyer, CEO of AstraZeneca’s subsidiary Alexion, AstraZeneca Rare Disease, said in a press release. Alexion Pharmaceuticals, before its acquisition by AstraZeneca, was the developer of Ultomiris.
“We look forward to the European Commission decision as we work to make Ultomiris available to people living with NMOSD in the EU and around the world,” Dunoyer added.
Regulatory applications seeking the therapy’s approval for NMOSD also are being reviewed by health authorities in the U.S. and Japan.
Recommendation based on positive Phase 3 trial data
In NMOSD, the immune system produces antibodies that wrongly attack and damage healthy cells in the nervous system. The most common target of these self-reactive antibodies is AQP4, a water channel protein present at the surface of neuron-supporting cells called astrocytes.
Ultomiris is designed to block the activation of a group of immune proteins called the complement cascade that play a central role in the disease-driving autoimmune attack. It specifically targets a complement protein called C5.
The therapy, administered directly into the bloodstream, works in essentially the same way as Soliris (eculizumab), a treatment approved in the EU and elsewhere for NMOSD patients with anti-AQP4 antibodies.
Both Ultomiris and Soliris were developed by Alexion. The newer therapy is engineered to be more stable in the body than Soliris, to require less frequent infusions. Specifically, after a loading dose, Ultomiris is given once every eight weeks, compared with the every-other-week regimen of Soliris.
“For patients with [AQP4-NMOSD], Ultomiris, the first and only long-acting C5 complement inhibitor, may have the potential to eliminate relapses, while also offering a convenient treatment schedule of infusions every eight weeks,” Dunoyer said.
The second-generation therapy is already widely approved to treat other disorders driven by complement cascade overactivation, including generalized myasthenia gravis, atypical hemolytic uremic syndrome, and paroxysmal nocturnal hemoglobinuria.
The sustained relapse risk reduction observed in the CHAMPION-NMOSD Phase [3] trial supports the critical role this long-acting C5 complement inhibitor may have for the NMOSD community.
The CHMP’s positive opinion on Ultomiris was based on data from a Phase 3 clinical trial called CHAMPION-NMOSD (NCT04201262), which tested the therapy in 58 adults with NMOSD and antibodies against AQP4.
Results showed that the rate of NMOSD relapses for Ultomiris-treated patients was markedly lower than that reported for patients given a placebo in an earlier trial of Soliris called PREVENT (NCT01892345). In fact, no patients experienced a relapse while on Ultomiris, with a median follow-up time of about 17 months.
“Even one NMOSD relapse can lead to devastating long-term effects like vision loss, chronic pain and paralysis, which underscores the need for treatment innovations that help prevent relapses and optimise disease management,” said Orhan Aktas, MD, a professor at Heinrich-Heine-University, in Germany.
“The sustained relapse risk reduction observed in the CHAMPION-NMOSD Phase [3] trial supports the critical role this long-acting C5 complement inhibitor may have for the NMOSD community,” Aktas added.
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