鶹ý

First NMO Treatment Approved

— Two others for neuromyelitis optica spectrum disorder also in the works

Last Updated November 11, 2019
MedpageToday

WASHINGTON -- The first treatment for neuromyelitis optica spectrum disorder (NMOSD), a relapsing autoimmune inflammatory condition, received FDA approval Thursday.

Eculizumab (Soliris), an injectable drug, was approved for NMOSD adults who are anti-aquaporin-4 (AQP4) antibody positive, the .

"Soliris provides the first FDA-approved treatment for neuromyelitis optica spectrum disorder, a debilitating disease that profoundly impacts patients' lives," said Billy Dunn, MD, director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research, in the agency's statement.

NMOSD, a disorder characterized by recurrent optic neuritis and myelitis that once was seen as a form of multiple sclerosis (MS), has a prevalence of 0.5 to 10 persons per 100,000, predominantly women. About 65%-88% of NMOSD patients produce antibodies that target the water-channel protein AQP4. Binding of AQP4-IgG antibodies to central nervous system cells is thought to trigger NMOSD attacks.

Eculizumab's effectiveness was seen in the randomized clinical trial of 143 NMOSD patients who had antibodies against AQP4 (anti-AQP4 positive). Compared with placebo, eculizumab by 94% over the 48-week trial. The drug also reduced the need for hospitalizations and the need for treatment of acute attacks with corticosteroids and plasma exchange.

"Untreated, this disease is devastating for patients," said Sean Pittock, MD, of the Mayo Clinic in Rochester, Minnesota, who presented PREVENT results at the American Academy of Neurology (AAN) annual meeting in May. "It can result in blindness or paraplegia in about half of patients within about 5 to 10 years."

Unlike MS, disability in NMOSD is due to attacks, not disease progression between attacks, and each attack leads to more damage. "If we can stop attacks, we can stop disability in this disease," Pittock told 鶹ý.

Because it blocks the terminal complement system, eculizumab increases the risk of meningococcal infection. The drug, which was previously approved to treat several diseases including generalized myasthenia gravis, carries a .

In PREVENT, all patients received meningococcal vaccination, and no cases of meningitis were reported. Higher rates of upper respiratory infection and headache were seen in the eculizumab-treated group, and one patient who had received concomitant azathioprine (Azasan) died from infectious pleural effusion after 108 weeks in the trial. Other adverse reactions reported by patients in the NMOSD clinical trial were colds, diarrhea, back pain, dizziness, influenza, joint pain, sore throat, and contusion.

Eculizumab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Prescribers must enroll in the REMS program, counsel patients about the risk of meningococcal infection, provide the patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccines. The drug must be dispensed with the FDA-approved patient Medication Guide.

Two other drugs being studied for NMOSD also had phase III data presented at the AAN meeting. In , AQP4-IgG positive patients treated with inebilizumab (MEDI-551) had a 77% reduction of relapse risk over placebo. And in , treatment with satralizumab (SA237) led to a 79% risk reduction of relapses vs placebo among the subgroup of patients who were AQP4-IgG positive.