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Eculizumab for Rare CNS Autoimmune Disease
The FDA has approved eculizumab (Soliris, Alexion Pharmaceuticals) injection for intravenous use to treat adults with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive. The central nervous system autoimmune disease mainly affects the optic nerves and spinal cord.
Eculizumab is the first FDA-approved treatment for NMOSD. Individuals with the disease typically have attacks of optic neuritis, which causes eye pain and vision loss, and attacks resulting in transverse myelitis, which can cause numbness, weakness, or paralysis of the arms and legs, and loss of bladder and bowel control. Most attacks occur in clusters, days to months to years apart, followed by partial recovery during periods of remission.
Approximately 50% of patients with NMOSD have permanent visual impairment and paralysis caused by NMOSD attacks. More women than men are affected by NMOSD and African Americans are also at greater risk of the disease. Approximately 4,000 to 8,000 people are believed to be affected by NMOSD in the United States.
NMOSD can be associated with antibodies that bind to a protein called aquaporin-4 (AQP4). Binding of the anti-AQP4 antibody appears to activate other components of the immune system, causing inflammation and damage to the central nervous system.
Eculizumab’s effectiveness was demonstrated in a 48-week clinical study of 143 patients with NMOSD who had antibodies against AQP4 (anti-AQP4 positive) and who were randomized to receive either eculizumab or placebo. Compared with placebo, eculizumab reduced the number of relapses by 94% over the course of the trial. Eculizumab also reduced the need for both hospitalizations and treatment of acute attacks with corticosteroids and plasma exchange.
The drug has a boxed warning indicating that life-threatening and fatal meningococcal infections have occurred in patients treated with eculizumab; such infections may become rapidly life-threatening or fatal if not recognized and treated early. No cases of meningococcal infection were observed in the clinical trial.
Eculizumab is available only through a Risk Evaluation and Mitigation Strategy (REMS). Prescribers must enroll in the REMS program, counsel patients on the risk of meningococcal infection, provide REMS educational materials to patients, and ensure patients are vaccinated with meningococcal vaccine(s).
The most frequently reported adverse reactions in the clinical trial include: upper respiratory infection, nasopharyngitis, diarrhea, back pain, dizziness, influenza, arthralgia, pharyngitis, and contusion.
First approved by the FDA in 2007, eculizumab is indicated for the destruction of red blood cells in adults with paroxysmal nocturnal hemoglobinuria; for adults and children with atypical hemolytic uremic syndrome; and for adults with myasthenia gravis who are anti-acetylcholine receptor antibody positive.
The FDA granted eculizumab an orphan drug designation for its use in NMOSD.
Source: FDA, July 2, 2019