FDA Approves Eculizumab for Neuromyelitis Optica Spectrum Disorder

Officials with the FDA today approved eculizumab (Soliris, Alexion Pharmaceuticals) for the treatment of neuromyelitis optica spectrum disorder (NMOSD), a rare autoimmune disease, in adults who are anti-aquaporin-4 (AQP4) antibody positive, according to a press release.

This approval follows an expedited 6-month priority review from the agency.

NMOSD is a severe, rare autoimmune condition that attacks the central nervous system without warning, resulting in relapses that can cause progressive and irreversible damage to the brain, optic nerve, and spinal cord. In the United States, African Americans are disproportionately affected by NMOSD and are more likely to experience more frequent and more severe attacks. NMOSD is often confused with other neurological illnesses, such as multiple sclerosis, which can lead to delays in diagnosis and treatment that can worsen disease progression.

With this approval, eculizumab is the first and only FDA-approved therapy indicated for the treatment of NMOSD.

Approximately 73% of patients with NMOSD have AQP4 auto-antibodies, according to Alexion. In patients with anti-AQP4 antibody-positive NMOSD, the body’s own immune system can turn against itself to produce auto-antibodies against AQP4. When these anti-AQP4 auto-antibodies bind, it activates the complement cascade, a part of the immune system. Activation of the complement cascade plays a role in severe and ultra-rare disorders, such as AQP4-positive NMOSD. Eculizumab, a complement inhibitor, works by inhibiting the C5 protein in the terminal part of the complement cascade.

In the phase 3 randomized, double-blind placebo controlled PREVENT trial, patients with NMOSD who were anti-AQP4 antibody positive were treated with eculizumab or a placebo. At 48 weeks, 98% of patients treated with eculizumab were relapse free compared with 63% of patients who received a placebo, according to the study.

Similarly, through 144 weeks, 96% of patients treated with eculizumab were relapse free compared with 45% of patients treated with a placebo. Those treated with eculizumab experienced similar improvement in time to first adjudicated on-trial relapse with or without concomitant treatment.

Among the patients treated solely with eculizumab without receiving other immunosuppressive therapies, 100% were relapse free at 144 weeks compared with 20% in the placebo group.

The most common adverse effects reported in the study that were associated with eculizumab were upper respiratory tract infection (29%), nasopharyngitis (21%), diarrhea (16%), back pain (15%), and dizziness (15%).

“In NMOSD, disease progression is driven by attacks, and so preventing future relapses is the primary goal of treatment,” John Orloff, MD, executive vice president and head of research and development at Alexion, said in a statement. “Today, for the first time, adults living with anti-AQP4 antibody-positive NMOSD have an approved treatment to reduce the risk of an unpredictable relapse — or attack.”

Reference

Alexion Receives FDA Approval Of Soliris (Eculizumab) For The Treatment of Adults With Neuromyelitis Optica Spectrum Disorder (NMOSD) Who Are Anti-Aquaporin-4 (AQP4) Antibody Positive [news release]. Alexion. https://news.alexion.com/press-release/product-news/alexion-receives-fda-approval-soliris-eculizumab-treatment-adults-neuromy. Accessed June 27, 2019.