Alexion and independent investigators are studying eculizumab as a potential treatment for patients with rare and serious neurologic disorders, including myasthenia gravis (MG) and neuromyelitis optica (NMO).
Myasthenia gravis is a rare, debilitating neurological disorder caused by uncontrolled complement activation resulting from auto-antibodies that recognize a specific target in the nerve-muscle junction. This causes tissue damage and interference with signaling between nerve and muscle fibers.1,4 Patients with myasthenia gravis initially experience weakness in their ocular (eye) muscles, and the disease typically progresses to the more severe and generalized form to include head, spinal, limb and respiratory muscles. Symptoms can include drooping eyelid, blurred vision, slurred speech, difficulty chewing or swallowing, weakness in the arms and legs and difficulty breathing.
There is no known cure for myasthenia gravis.2 Common treatments include medications (anticholinesterase agents, corticosteroids, immunosuppressive agents or cytotoxic therapy), thymectomy (surgical removal of the thymus gland) and plasma exchange.2,3 In a Phase 2 Alexion-sponsored study in patients with severe and refractory generalized myasthenia gravis, an ultra-rare and debilitating form of the disease, eculizumab demonstrated a strong clinical signal for meaningful disease improvement. Based on these encouraging results Alexion is now planning a larger, prospective placebo-controlled study in patients with severe and refractory myasthenia gravis.
Neuromyelitis Optica (NMO)
NMO is syndrome of the central nervous system (CNS) in which immune system cells and antibodies attack and destroy myelin, a fatty substance that surrounds nerve fibers and helps nerve signals move from cell to cell. As a result, patients with NMO develop optic neuritis, which causes eye pain and vision loss, and transverse myelitis, which causes weakness, numbness, and sometimes paralysis of the arms and legs, as well as sensory disturbances and loss of bladder and bowel control. Despite currently available treatment – including a corticosteroid drug to stop NMO attacks and an immunosuppressive drug to prevent subsequent attacks –most patients with NMO experience an unpredictable, relapsing course of disease with cumulative disability.5
Eculizumab is currently being evaluated in an investigator-initiated Phase 2 trial in patients with NMO.
- Conti-Fine BM, Milani M, Kaminski HJ. Myasthenia gravis: past, present, and future. J Clin Invest 2006 Nov;116(11):2843-54.
- Myasthenia Gravis Foundation of America, Inc. (MGFA) Website. Treatment for MG. June 2010. Available at http://www.myasthenia.org/WhatisMG/TreatmentforMG.aspx. Accessed on September 7, 2011.
- Garcia-Carrasco M, Escarcega RO, Fuentes-Alexandro S, Riebeling C, Cervera R. Therapeutic options in autoimmune myasthenia gravis. Autoimmun Rev 2007 Jun;6(6):373-8.
- Tüzün E, Huda R, Christadoss P. Complement and cytokine based therapeutic strategies in myasthenia gravis, J Autoimmunity 2011 May 31 [Epub ahead of print].
- National Institute of Neurological Disorders and Stroke. National Institutes of Health. NINDS Neuromyelitis Optica Information Page. Available at http://www.ninds.nih.gov/disorders/neuromyelitis_optica/neuromyelitis_optica.htm. Accessed April 19, 2011.
- Veldman A, et al. Successful treatment of molybdenum cofactor deficiency type A with cPMP Pediatrics. 2010 May;125(5):e1249-54.