The Food and Drug Administration has really been buckling down this year, and rightfully so, demanding more evidence of success and deeper understanding of potential safety risks of new manufactured medications. Merck KGaA in Germany is no different, and today the giant announced today that their new drug application (NDA) for Cladribine Tablets, used to treat relapsing-remitting multiple sclerosis (MS) is to this point, denied approval in the United States. Cladribine Tablets were approved in Russia in July 2010 and in Australia in September 2010 as a treatment of relapsing-remitting MS and are under regulatory review in other countries.
Relapsing/Remitting Multiple Sclerosis (RRMS) is one of four internationally recognized forms of Multiple Sclerosis.
RRMS is characterized by relapses (also known as exacerbations) during which time new symptoms can appear and old ones resurface or worsen. The relapses are followed by periods of remission, during which time the person fully or partially recovers from the deficits acquired during the relapse.
Relapses can last for days, weeks or months and recovery can be slow and gradual or almost instantaneous. The vast majority of people presenting with Multiple Sclerosis are first diagnosed with relapsing/remitting. This is typically when they are in their twenties or thirties, though diagnoses much earlier or later are known. Twice as many women as men present with this variety.
The FDA has requested that Merck provide an improved understanding of safety risks and the overall benefit-risk profile either through additional analyses or by additional studies.
Fereydoun Firouz, President and CEO of Merck’s U.S. subsidiary EMD Serono, Inc commented:
“Our commitment to transform the way people living with MS approach their therapy options remains steadfast. We look forward to working with the FDA to address the safety issues in its letter and will continue to move toward identifying a potential path that provides patients and physicians the opportunity to have access to Cladribine Tablets in the treatment of MS.”
Cladribine is a small molecule that may interfere with the behavior and the proliferation of certain white blood cells, particularly lymphocytes, which are thought to be involved in the pathological process of MS.
During relapses, myelin, a protective insulating sheath around the nerve fibers (neurons) in the white matter regions of the central nervous system (CNS), is damaged in an inflammatory response by the body’s own immune system. This causes a wide variety of neurological symptoms that vary considerably depending on which areas of the CNS are damaged.
Immediately after a relapse, the inflammatory response dies down and a special type of glial cell in the CNS (called an oligodendrocyte) sponsors remyelination, a process whereby the myelin sheath around the axon is repaired. It is this remyelination that is responsible for the remission.
Approximately 50% of patients with RRMS convert to Secondary Progressive Multiple Sclerosis (SPMS) within 10 years of disease onset. After 30 years, this figure rises to 90%.
Medical staff would usually define a relapse as an episode of neurological symptoms that happens at least 30 days after any previous episode began. This episode lasts at least 24 hours. Other possible causes for the appearance of these symptoms also have to be ruled out before deciding it is an MS relapse. Other causes could include infection or something else that raises the body’s temperature and makes symptoms worse.
Sources: The Multiple Sclerosis Society and The Merck Group
Written by Sy Kraft, B.A.