Laquinimod – new promising treatment of multiple sclerosis
Laquinimod is a once-daily novel oral immunomodulatory agent developed as a disease modifying treatment for multiple sclerosis, MS, which Active Biotech has licensed to Teva Pharmaceutical Industries Ltd. (2004). Teva also performs a Phase II study of laquinimod in Crohn's disease.
Multiple sclerosis
Multiple sclerosis (MS) is a chronic, progressive disease affecting the central nervous system. The disease affects the central nervous system (the brain and spinal cord). The symptoms are caused by the body’s own immune system attacking and damaging the myelin sheaths surrounding nerve fibers. This causes inflammation within the central nervous system causing the patient to suffer relapses and disease progression. The etiology of the disease is unknown, but is assumed to depend, like other autoimmune diseases, on both genetic and environmental factors.
There are various forms of MS, the most common is relapsing remitting MS ("RRMS"). It is characterized by unexpected recurring relapses that can last from a few days to a few weeks and are followed by complete or partial remission. In approximately 80 percent of all patients, the disease begins as RRMS but most develop after some ten or so years into secondary progressive MS (“SPMS”), which is characterized by a gradually increasing degree of disability, without the recovery periods.
MS primarily affects young and middle-aged people. The disease often first appears when the patient is between 20 and 50 years old, and the number of women affected is twice as high as the number of men. A total of about two million people throughout the world suffer from MS. The disease is more common in the northern hemisphere. The Nordic region, the British Isles and North America are regarded as high-risk areas.
There are currently three types of drugs for the treatment of MS: interferons, glatiramer acetate and natalizumab. The drugs reduce the number of relapses and are therefore all approved for treatment of MS patients with relapses. The total market for MS pharmaceuticals amounted to USD 8.8 billion in 2008 (Therapeutic Categories Outlook, Cowen & Co, March 2009). Since MS patients must be on medication throughout their lifetime, an oral treatment creates a substantial advantage compared with existing products on the market, all of which must be injected.
Crohn's disease
Crohn's disease is a chronic inflammatory condition that affects the gastrointestinal tract. The symptoms of Crohn's disease can vary significantly among afflicted individuals. The main gastrointestinal symptoms are abdominal pain, diarrhea, vomiting, or weight loss. Crohn's disease can also cause complications outside of the gastrointestinal tract such as skin rashes, arthritis, and inflammation of the eye.
The precise cause of Crohn's disease is not known. The disease occurs when the immune system attacks the gastrointestinal tract and for this reason, Crohn's disease is considered to be an autoimmune disease. This autoimmune activity produces inflammation in the gastrointestinal tract, and therefore Crohn's disease is classified as an inflammatory bowel disease, IBD.
Ongoing research
The Allegro study (assessment of oral laquinimod in preventing progression of multiple sclerosis), which is a global, pivotal, double-blind, Phase III study designed to evaluate the efficacy, safety and tolerability of laquinimod versus placebo in the treatment of RRMS, has been in progress since November 2007. The Allegro study was fully recruited in November 2008 encompassing 1,000 patients. The treatment administered is a 0.6 mg tablet of laquinimod once a day or placebo. The study is scheduled to continue for 24 months with the possibility to extend to 30 months.
A second pivotal Phase III study, Bravo (benefit-risk assessment of Avonex® and laquinimod), which is a global, multi-center, randomized, placebo-controlled 24 months study with parallel groups, was initiated in April 2008. The study will compare the effect of once-daily orally administered laquinimod 0.6 mg with placebo and also provide risk-benefit data in relation to treatment with a product presently established in the market and administered by injection (Avonex®). The Bravo study was fully recruited in June 2009 encompassing 1,200 patients. For further information about the Bravo study, please visit www.tevaclinicaltrials.com/hcp/bravo_info.aspx.
Detailed information regarding the Phase III studies is published on www.TevaClinicalTrials.com and www.clinicaltrials.gov.
Current results
In February 2009, oral laquinimod received a Fast Track designation from the U.S. Food and Drug Administration (FDA). Drugs designated for Fast Track are intended for the treatment of a serious or life-threatening condition and have demonstrated the potential to address unmet medical needs. Fast Track designation can potentially facilitate development and expedite the review process. This may allow laquinimod to enter the market as soon as late 2011.
In June 2008, data published in the medical journal The Lancet showed that the treatment using tablet-form laquinimod significantly reduced disease activity in the central nervous system of RRMS patients by 60% (median), measured with magnetic resonance imaging (MRI), compared with placebo, and was well-tolerated. Most of the patients who participated in the study are continuing to receive treatment with laquinimod in an open extension study. The article, entitled “Effect of Laquinimod on MRI-monitored disease activity in patients with RRMS: a multicenter, randomized, double-blind, placebo-controlled phase IIb study,” was published in The Lancet Volume 371, Issue 9630.