FDA Approves First Drug for Neuromyelitis Optica

Deborah Brauser

June 27, 2019

The US Food and Drug Administration (FDA) has approved the humanized monoclonal antibody eculizumab (Soliris, Alexion Pharmaceuticals) for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults who test positive for anti-aquaporin-4 (AQP4) autoantibodies, the agency announced in a statement earlier today.

This makes eculizumab the first FDA-approved drug for this indication.

"This approval changes the landscape of therapy for patients with NMOSD," Billy Dunn, MD, director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research, said in a news release.

He added that NMOSD is a "debilitating disease that profoundly impacts patients' lives."

The approval was based in large part on results from the phase 3 multicountry PREVENT trial, which were presented at the recent American Academy of Neurology (AAN) 2019 Annual Meeting and were simultaneously published online in the New England Journal of Medicine.

As reported at the time by Medscape Medical News, 43% of the 143 participants with AQP4 antibody-positive NMOSD who received placebo experienced adjudicated relapses, vs 3% of those who received intravenous eculizumab. For the latter group, annualized relapse rates were also lower.

Asked to comment on the approval, Eddie Patton, MD, neurologist and clinical assistant professor in the Department of Neurology and Neurosurgery, University of Texas, Houston, noted that the drug "gives us a very focused treatment" for patients with NMOSD.

"I can't underscore enough the burden that this disease typically has on patients. So it's exciting to have something that's targeted and has been shown to be more effective, as far as reducing relapses," Patton told Medscape Medical News.

Boxed Warning

Eculizumab is a C5 complement inhibitor.

NMOSD, which is also often referred to as NMO, is a rare, complement-mediated disorder of the central nervous system. It is characterized by relapses that are associated with increasing disability, including blindness and paralysis. The FDA notes that about 4000 to 8000 patients are affected by NMOSD in the United States.

In addition, about 73% of patients with the disorder have anti-AQP4 antibodies. NMOSD primarily affects women.

In PREVENT, 91% of the participants were women; the mean age at initial receipt of the drug was 44.3 years. The trial was conducted at sites in 18 countries.

Over 48 weeks, treatment with eculizumab reduced the number of NMOSD relapses by 94% compared with placebo treatment.

The most commonly reported adverse events in the trial were upper respiratory infection, nasopharyngitis, diarrhea, and back pain.

The drug "has a boxed warning to alert health care professionals and patients that life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris, and that such infections may become rapidly life-threatening or fatal if not recognized and treated early," the FDA noted in its release.

In addition, caution should be used when administering the drug to patients who have any other infection, the agency added.

Of note, no cases of meningococcal infection were observed in the PREVENT trial.

More Options Coming?

Eculizumab will be available only through a risk evaluation and mitigation strategy program and "must be dispensed with the FDA-approved patient Medication Guide," the FDA said.

The agency granted priority review of eculizumab for NMOSD in February. Filing is currently under review in the European Union and is expected to occur in Japan later this year.

"Having an approved therapy for this condition is the culmination of extensive work we have engaged in with drug companies to expedite the development and approval of safe and effective treatments for patients with NMOSD, and we remain committed to these efforts for other rare diseases," Dunn said.

The drug was previously approved by the FDA for treating paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, and generalized myasthenia gravis.

"Today's approval represents an important milestone for the NMOSD community," Victoria Jackson, cofounder of the Guthy-Jackson Charitable Foundation, a nonprofit organization dedicated to NMOSD, said in a release from Alexion.

"The FDA approval of Soliris is the beginning of a new era for these NMOSD patients as we continue on our mission to cure this life-threatening disease," Jackson added.

Commenting on the PREVENT results at the AAN meeting, Asaff Harel, MD, a neurologist specializing in neuroimmunology at the Northwell Multiple Sclerosis Center at Lenox Hill Hospital, New York City, told Medscape Medical News that preventing relapses "is paramount" for these patients.

"I think having a medication that is approved by the FDA for [neuromyelitis optica] would be powerful," he added.

Harel noted that a few other treatments for this indication are currently in the pipeline. "I think we're going to see more and more options, which will lead to better control of the condition overall," he said.

Patton is on the speaker's bureau for Alexion. Harel has disclosed no relevant financial relationships.

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