FDA approves Ultomiris to treat adults with AQP4-related NMOSD
US approval of Soliris successor follows those in EU, Japan and Canada
The U.S. Food and Drug Administration (FDA) has approved Ultomiris (ravulizumab-cwvz) to treat adults with neuromyelitis optica spectrum disorder (NMOSD) who are positive for antibodies against the aquaporin-4 (AQP4) protein.
About 75% of people with NMOSD produce antibodies that bind to AQP4, according to the therapy’s developer, Alexion Pharmaceuticals, now a subsidiary of AstraZeneca known as Alexion, AstraZeneca Rare Disease.
Ultomiris is the successor of Soliris (eculizumab), an older NMOSD-approved therapy also developed by Alexion.
Both therapies, administered directly into the bloodstream, work by blocking the activity of a complement protein called C5. The complement cascade is a group of proteins with a central role in the autoimmune attack that drives NMOSD. But while Soliris is given every other week, Ultomiris is administered every other month due to its long-acting effects, which may help to ease the treatment burden for patients.
“Alexion has been at the forefront of innovation in NMOSD, striving to offer patients a future without fear of life-altering or even fatal relapses,” Marc Dunoyer, CEO of Alexion, said in a company press release.
“Building on the established efficacy of C5 [blocking] for people living with [anti-AQP4] NMOSD, we are proud to deliver a transformative, long-acting treatment option that has the potential to eliminate relapses with a convenient dosing schedule every eight weeks,” Dunoyer said.
Restricted program in place for Ultomiris due to meningococcal infection risk
Ultomiris’ approval for AQP4-related NMOSD comes within a year of similar regulatory decisions in the European Union, Japan, and most recently Canada. These approvals were based mainly on data from a Phase 3 clinical trial called CHAMPION-NMOSD (NCT04201262).
That study tested Ultomiris in 58 adults with AQP4-related NMOSD, and results showed none of the patients experienced a relapse over a median treatment duration of 1.5 years. Relapses, also called flares or attacks, are marked by a sudden increase in symptom severity and/or the appearance of new symptoms.
Given that relapses can lead to progressive and permanent disability, preventing relapses is the “primary goal” in NMOSD treatment, according to Sean J. Pittock, MD, director of the Mayo Clinic’s center for multiple sclerosis and autoimmune neurology, and the lead investigator on the trial.
With [this] FDA approval, patients now have the option of a long-acting C5 inhibitor treatment.
The most common side effects of Ultomiris seen in NMOSD patients during the trial included COVID-19 infection, headache, back pain, urinary tract infection, and joint pain.
“C5 inhibition has been proven to offer efficacy in reducing the risk of NMOSD relapses by blocking the complement system, a part of the immune system, from attacking healthy cells in the spinal cord, optic nerve and brain,” Pittock said.
“With [this] FDA approval, patients now have the option of a long-acting C5 inhibitor treatment,” Pittock said.
Ultomiris already is available in the U.S. for treating other diseases driven by the complement system, including myasthenia gravis and paroxysmal nocturnal hemoglobinuria.
However, because the immunosuppressing therapy can increase the risk of meningococcal infections — a type of bacterial infection in the brain that can be life-threatening — it is only available through a restricted program called Ultomiris REMS.
The restricted program aims to improve monitoring so that if meningococcal infections occur they can be identified and addressed quickly before causing serious problems.
As a condition of its approval of Ultomiris for NMOSD, the FDA previously required that this program be modified to include an extra step of validating patients’ meningococcal vaccination status or administration of preventive antibiotics before treatment.
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