Possible good news for patients with neuromyelitis optica (aka Devic’s syndrome) and for stock holders of Alexion Pharmaceuticals. The drug Soliris (eculizumab) may be a safe and effective treatment for that condition. In an open label pilot study examining the effects of eculizumab in patients with AQP40IgG-positive relapsing neuromylelitis optica spectrum disorder, Sean Pittock and colleagues found eculizumab to be safe and effective.
Their study published in Lancet Neurology examined 14 female patients with confirmed AQP40IgG-positive relapsing neuromylelitis optica. The study was conducted at 2 Mayo Clinic Centers (Rochester MN and Scottsdale AZ). After 12 months of treatment with eculizumab, the median number of attacks per year fell from 3 (range, 2-4) before treatment to 0 (0-1) during treatment (p<0.0001). An attack was defined as a new worsening of neurological function (visual loss, limb weakness or sensorysymptoms, and bladder or bowel dysfunction) lasting for more than 24 hours and not attributable to an identifiable cause. In addition, the study reported that no patient had worsened disability by any outcome measure while the drug was given and it appeared to be well tolerated [e.g., Median EDSS score improved from 4.3 (range 1.0–8.0) pretreatment to 3.5 (0-8.0) during treatment (mean difference –0.7 [95% CI –1.2 to –0.2]; p=0.0078). Two patients improved by two points and three improved by one point on the Hauser ambulation index; no change was recorded for the other patients. Visual acuity had improved in at least one eye by one point in four patients, and by two points in one patient;no change was recorded for the other patients].
Interestingly, 12 of the patients were followed-up one year after being taken off the drug. During that second year, 9 attacks in 5 patients were reported.
Neuromyelitis optica is a severe inflammatory CNS disorder that results in inflammation of the eye nerves (optic neuritis) and the spinal cord (myelitis). This can lead to blindness in one or both eyes, weakness or paralysis in the legs or arms, painful spasms, loss of sensation, and bladder or bowel dysfunction from spinal cord damage. These attacks may be reversible, but can be severe enough to cause permanent visual loss and problems with walking. For many years, neuromyelitis optica was thought to be a severe variant of multiple sclerosis but the two are now considered two distinct conditions. Most patients (70%) with neuromyelitis optica have an antibody (AQP40IgG) that is not found in people with multiple scelerosis. The antibody is used as a biomarker and is also believed to be involved in the disease’s expression.
Alexion Pharmaceutical’s eculizimab has orphan drug indications for two rare diseases – paroxysmal nocturnal hemoglobinuria (PNH) and atypical Hemolytic Uremic Syndrome (aHUS). Alexion is not stopping there. They are sponsoring numerous ultra rare disease programs with eculizumab, including neuromyelitis optica. Eculizumab is monoclonal IgG antibody that may disrupt the AQP4-IgG believed to be involved in disease expression. The trial by Pittock et al was funded by Alexion.
In an editorial in The Lancet Neurology, Dr. Friedemann Paul of NeuroCure Clinical Research Center and Department of Neurology, Clinical and Experimental Multiple Sclerosis Research Center, Charité University Medicine Berlin, noted that while the study is small and its open label design limits the conclusions that can be made, Dr. Paul stated that the study provides two important lessons, “First, the clinical experience with eculizumab supports basic research data, suggesting that complement activation is key to the damage cascade of neuromyelitis optica. Second, understanding of the mechanisms in neuromyelitis optica immunopathogenesis is a prerequisite for disease specific treatments. Overall, this laudable approach by Pittock and colleagues shows translational medicine at its best and will probably fuel the search for improved treatments for neuromyelitis optica.”
At present, there is no indicated treatment for neuromyelitis optica and clinicians usually treat an initial attack of neuromyelitis optica with a combination of a corticosteroid drug to stop the attack, and an immunosuppressive drug for prevention of subsequent attacks.