A new treatment for multiple sclerosis (MS) reduces MRI disease activity* and is well-tolerated in patients with the relapse-remitting form of the condition. The treatment is also oral and thus offers advantages to patients over conventional injected treatments. The promising results from this phase II study are reported in an Article in this week's edition of The Lancet.
MS is an immune-mediated disease of the central nervous system, affecting predominantly 'white matter'- ie, the tissues in the brain and the other parts of the nervous system which transmit messages between 'gray matter' where nerve bodies are found. Drugs available at the moment focus on the inflammatory aspects of MS, which predominate in the relapse-remitting form of the disease. These drugs include glatiramer acetate, interferon β, natalizumab, and mitoxantrone, and all are injectable, Thus the availability of an oral agent could be a major advantage for patients in terms of convenience. Professor Giancarlo Comi, Institute of Experimental Neurology, University Vita-Salute, Milan, Italy and colleagues did a randomised phase II trial to test the efficacy, safety, and tolerability of two doses of laquinimod versus placebo.
The trial involved 51 centres in nine countries, and patients were eligible if they had had one or more relapses in the year before entry and at least one gadolinium enhancing (GdE) lesion** on screening MRI. A total of 306 patients aged 18-50 years were enrolled, with 102 randomly assigned to placebo, 98 to laquinimod 0.3mg daily, and 106 to laquinimod 0.6mg daily. Brain MRI scans and clinical assessments were done four weeks before the trial started, at the start (baseline), then every four weeks for nine months. Numbers of GdE lesions were measured at weeks ,12, 16, 20, 24, 28, 32 and 36.
The researchers found that, compared with placebo, laqunimod 0.6 mg per day showed a 40.4% reduction of the mean number of GdE lesions over the last four scans compared with baseline, while laquinimod 0.3 mg per day showed no statistically significant effects vs placebo. Both doses of laquinimod were well tolerated, with only two serious but reversable adverse events connected with the drug, but with no clinical consequences. Two patients stopped treatment as one had persistent elevations in liver enzymes, while another had inherited thrombophilia and experienced an event of Budd-Chiari syndrome -- a partial blockage of the venous outflow from the liver.
The authors conclude: "Overall, the efficacy and safety profile emerging from this and from a previous phase II clinical trial, in combination with the oral route of administration, make laquinimod a promising therapeutic opportunity for patients with relapse remitting multiple sclerosis. The benefits and risks of laquinimod treatment are now being further assessed in a large-scale phase III trial."
In an accompanying Comment, Dr B Mark Keegan and Dr Brian G Weinshenker, Department of Neurology, Mayo Clinic, Rochester, MN, USA, say laquinimod will need to go through head-to-head trials with other multiple sclerosis drugs to demonstrate superiority or at least equivalence. They add that, as for any new drug, safety is paramount and safety issues will need to be carefully monitored since serious adverse events are commonly not evident until phase III studies are started or sometimes until after approval.
Notes to editors:
*The higher the disease activity in MS as measured by Magnetic Resonance Imaging (MRI) is, the higher the chances are for the patients to experience relapses and eventually to accumulate neurological disability
**gadolinium enhancing lesions: a marker of the inflammatory activity of multiple sclerosis
Professor Giancarlo Comi, Institute of Experimental Neurology, University Vita-Salute, Milan, Italy T) +39 02 26432990 / +39 02 26433087 E) g.comi@hsr.it
Dr B Mark Keegan and Dr Brian G Weinshenker, Department of Neurology, Mayo Clinic, Rochester, MN, USA contact by e-mail only E) keegan.bmark@mayo.edu
http://multimedia.thelancet.com/pdf/press/multiplesclerosis.pdf
Journal
The Lancet