FDA approves Ultomiris for neuromyelitis optica spectrum disorder

Issue: May 25, 2024

ByAlex Young

Fact checked byChristine Klimanskis, ELS

Key takeaways:

Ultomiris is a C5 complement inhibitor for neuromyelitis optica spectrum disorder.
Trial patients did not experience any relapses over a median treatment duration of 73 weeks.

Perspective from Osama Al Deyabat, MD, Saif AlRyalat, MD, and Andrew G. Lee, MD

The FDA approved Ultomiris for the treatment of adults with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder, according to a press release from Alexion.

The approval was based on positive results from the phase 3 CHAMPION-NMOSD trial that compared Ultomiris (ravulizumab-cwvz), a long-acting C5 complement inhibitor, with an external placebo arm from the pivotal Soliris (eculizumab) PREVENT clinical trial.

Generic FDA News infographic — The FDA approved Ultomiris for the treatment of adults with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder, according to a press release from Alexion.

The primary endpoint was time to first on-trial relapse as confirmed by an independent adjudication committee. There were no relapses observed in patients on Ultomiris with a median treatment duration of 73 weeks.

Additionally, no new safety signals were observed in the trial.

“Building on the established efficacy of C5 inhibition for people living with AQP4 Ab+ 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 8 weeks,” Marc Dunoyer, CEO of Alexion, said in the release.

Perspective

Osama Al Deyabat, MD, Saif AlRyalat, MD, and Andrew G. Lee, MD

You can have good, you can have it fast, you can have it cheap — pick two.

New FDA-approved biologics including monoclonal antibodies have dramatically changed the landscape for treatment in neuromyelitis optica spectrum disorder (NMOSD). Recently, ravulizumab has joined the armamentarium for the devastating autoimmune antibody-mediated disorder NMOSD. Prevention of recurrence is critical in NMOSD as even a single attack of optic neuritis or myelitis can lead to blindness or paralysis, respectively.

Since 2019, three monoclonal antibodies targeting different molecules — satralizumab (interleukin-6), inebilizumab (CD19) and eculizumab (C5) — in the NMOSD pathway were approved. Eculizumab targets the downstream C5 common complement pathway and demonstrated rapid and effective disease control in the PREVENT trial. Administered intravenously once every 2 weeks, eculizumab was associated with a 94.2% reduction in NMOSD relapse risk compared with placebo. However, its main drawbacks were the cost and frequent dosing requirements. The recently approved new drug ravulizumab may address some of the challenges without compromising efficacy, as it can be administered once every 8 weeks after the loading dose. In the CHAMPION-NMOSD trial, an open-label study comparing ravulizumab patients with external controls from the PREVENT trial, no relapses occurred over a median duration of 73 weeks. In addition to safety and efficacy, however, the other issue with ravulizumab, as with all these newer biologics, is the relatively high cost of therapy.

As newer, safer and more effective treatment options become available for NMOSD, there is continued hope for patients with this potentially devastating neurologic disorder. Continued research in drug design (eg, glycoengineering) and optimization of dose, route and frequency of administration are needed so that these agents can be better, faster and cheaper.