FDA Approves Eculizumab for Treatment of Neuromyelitis Optica Spectrum Disorders

The Food and Drug Administration (FDA) has approved eculizumab (Soliris; Alexion, Boston, MA) for treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4 (anti-AQP4) antibody positive. Approximately 73% of people with NMOSD are AQP4 positive. 

Of people with anti-AQP4-postive NMOSD, 96% of those who were treated with eculizumab (n = 96) were relapse free for 144 weeks (almost 3 years) compared with 45% of those treated with placebo (n = 47). People treated with eculizumab had similar improvements in time to first relapse whether or not they were receiving other treatments. Of those whose only immunosuppressive treatment was eculizumab (n = 21), no relapse occurred over the 144 weeks, whereas 80% of those treated with placebo and no other immunosuppressive treatment (n = 13) did experience relapse. 

“NMOSD is a serious disease with devastating consequences,” said Michael Levy, MD, PhD, a consultant to Alexion and Associate Professor of Neurology at Massachusetts General Hospital in Boston. “Each attack can result in potentially irreversible consequences—causing blindness or losing the ability to walk—so preventing relapse is the primary goal of treatment. With the approval of Soliris, there is now for the first time an FDA-approved treatment available to NMOSD patients to help reduce the risk of relapse.”

“Today's approval represents an important milestone for the NMOSD community,” said Victoria Jackson, co-founder of the Guthy-Jackson Charitable Foundation (GJCF), a nonprofit organization dedicated to funding research and raising awareness about NMOSD. “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.”

Previously known as Devic’s Disease, NMOSD is often confused with other neurologic illnesses such as multiple sclerosis (MS). Anti-AQPR-positive NMOSD affects African-Americans and women disproportionately and presents with optic neuritis, blindness, transverse myelitis, or paralysis. When anti-AQP4 auto-antibodies activates complement, neuroinflammation, demyelination and neuron death occur. Eculizumab is a first-in-class complement inhibitor of C5 protein in the terminal part of the complement cascade. 

Eculizumab has previously been approved for the treatment of thrombocytopenia in adults with paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome-related thrombotic microangiopathy in adults and children, and anti-acetylcholine receptor (anti-AChR) antibody positive myasthenia gravis. The safety profile of eculizumab in studies for treatment of NMOSD was consistent with that seen in previous studies, and the most common adverse events were upper respiratory tract infection (29% with eculizumab vs 13% with placebo), nasopharyngitis (21% vs 19%), diarrhea (16% vs 15%), back pain (15% vs 13%) and dizziness (15% vs 13%). Serious adverse events included pneumonia (3 people treated with eculizumab and 1 treated with placebo) and cellulitis, sepsis, and urinary tract infection (2 people treated with eculizumab for each event). One person with a history of comorbid pulmonary disease and active smoking who received both eculizumab and supportive immunosuppressant therapy died from infectious pleural effusion. No cases of meningococcal infection, which has been seen in other studies of eculizumab were observed in the studies for NMOSD.

Eculizumab has a boxed alert for meningococcal infections which have occurred with some fatalities with treatment. The drug is available under a risk evaluation and mitigation strategy, prescribers must be enrolled in this program in order to prescribe eculizumab and must monitor patients for signs of meningococcal infection.