Currently, people with multiple sclerosis only have injectable medicine to choose from as a treatment for their disease. But an oral medication for MS is moving forward in a series of clinical trials co-sponsored by two pharmaceutical companies.
Oral Nucleoside Analog Scrutinized
The drug is an oral form of cladribine (KLA-druh-bene) known as Mylinax®, a type of nucleoside analog designed to interfere with the production and behavior of certain white blood cells—mostly lymphocytes—that are involved in the origins and progression of multiple sclerosis.
Mylinax® is about to be tested in a Phase III clinical trial, typically the final phase in a series of trials performed prior to a manufacturer's request for approval to the Food and Drug Administration.
"With the initiation of the Phase III program of Mylinax®, we are getting closer to realizing our objective to bring the first oral disease-modifying treatment to people with multiple sclerosis," said Ernesto Bertarelli, CEO of Serono, one of two manufacturers that reached an agreement to develop the medication.
A Series of Positive Outcomes
Previous clinical trials of injectable cladrabine showed positive effects of the drug.1-4 In one trial by doctors at the University of Western Ontario in Canada,3 159 patients with primary and secondary progressive MS were given two doses of cladrabine or an intervention with no therapeutic value known as placebo for a year. The researchers then assessed the results by taking magnetic resonance imaging (MRI) scans of each patient every 6 months during the study. MRI scans allow doctors to measure brain lesions that occur in MS.
While disability between all patients did not change on average, after the study, the researchers noted that both doses of cladribine were more effective than the placebo in terms of reducing the number and volume of brain lesions.
In an earlier, smaller trial from the Scripps Research Institute in La Jolla, California,4 doctors also compared the efficacy of cladrabine to placebo in a group of 51 patients who received treatment over 4 months.
The researchers evaluated the condition of each patient's cerebrospinal fluid and MRI results at 6 and 12 months of treatment. As in the study from Canada, they found patients taking cladrabine had better outcomes than those on placebo. Only one patient had significant toxicity to the drug, but recovered within several months.
"We are very pleased to have reached this important milestone in the development of Mylinax® as a novel therapy for multiple sclerosis," said Phillip Frost, chairman and CEO of IVAX Corporation, which is launching the new trial in conjunction with Serono.
A Disease of Demyelination
Multiple sclerosis is a common disease of the central nervous system, which makes up the brain and spinal cord. Essentially, it is an inflammatory demyelinating (deh-MYE-eh-lin-ay-ting) disease; that is, it is characterized by an abnormal immune system attack against myelin in the central nervous system. Myelin is a fatty material that insulates nerves, much like the covering of an electrical wire, which allows the nerve to transmit impulses rapidly. It is the speed and efficiency with which these impulses are conducted that permits smooth, rapid and coordinated movements to be accomplished with little conscious effort.5
In MS, the loss of myelin results in disruption in the ability of these nerves to conduct their electrical impulses to and from the brain. This is manifested as the symptoms seen in MS.
1. Niezgoda A, Losy J, Mehta PD. Effect of cladribine treatment on beta-2 microglobulin and soluble intercellular adhesion molecule 1 (ICAM-1) in patients with multiple sclerosis. Folia Morphol (Warsz) 2001 Aug;60(3):225-8.
2. Janiec K, Wajgt A, Kondera-Anasz Z. Effect of immunosuppressive cladribine treatment on serum leukocytes system in two-year clinical trial in patients with chronic progressive multiple sclerosis. Med Sci Monit 2001 Jan-Feb;7(1):93-8.
3. Rice GP, Filippi M, Comi G. Cladribine and progressive MS: clinical and MRI outcomes of a multicenter controlled trial. Cladribine MRI Study Group. Neurology 2000 Mar 14;54(5):1145-55.
4. Sipe JC, Romine JS, Koziol JA, McMillan R, Zyroff J, Beutler E. Cladrabine in treatment of chronic progressive multiple sclerosis. Lancet 1994 Jul 2;344(8914):9-13.
5. Multiple Sclerosis International Federation. What is MS? Available at: http://www.msif.org/en/ms_the_disease/what_is_ms.html. Accessed January 21, 2005.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
