Laquinimod
Laquinimod is an experimental new drug treatment for people with relapsing remitting multiple sclerosis (MS) that is taken by mouth.
Other names: ABR-215062
In development for: Relapsing remitting multiple sclerosis (MS)
Status: Phase III
Last updated: June 2011
How does it work?
Laquinimod affects the levels of certain cytokines (substances released by immune cells) and reduces the passage of immune cellls into the brain and spinal cord. Laboratory investigations have suggested it may have both neuroprotective and anti-inflammatory actions.
How is it given?
Laquinimod is taken orally as tablets.
Clinical studies
A phase II study of oral laquinimod (0.3mg) concluded that it was well tolerated and effective in suppressing development of active MRI lesions in 209 people with relapsing remitting MS. Treatment over six months resulted in a 44% decrease in MRI disease activity. People with disease activity at the start of the study showed a decrease of 52%1.
In a second phase II study of 306 people with relapsing remitting MS, laquinimod was given at two different doses (0.3 and 0.6mg) for nine months. The higher dose (0.6 mg per day) significantly reduced the number of active lesions seen in scans from month six onwards. The lower dose (0.3 mg) was not effective2.
Upon completion of these phase II studies, participants were enrolled into a 36-week extension study during which all study participants received a daily dose of oral laquinimod of either 0.3mg or 0.6mg. An average 52% reduction in the number of active lesions on MRI was seen in the group who were switched from placebo to either the 0.3mg or 0.6mg dose of laquinimod in the extension study, while the reduction in the average number of active lesions seen in the groups receiving laquinimod in both the initial study and the extension study, was sustained at around 40%3.
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ALLEGRO (Safety and Efficacy of Orally Administered Laquinimod for Treatment of Relapsing Remitting Multiple Sclerosis)
In the phase III trial ALLEGRO, over 1100 people with relapsing remitting MS in 24 countries received a daily oral dose of 0.6mg laquinimod or a placebo (dummy pill) for two years. Those on laquinimod showed a 23% reduction in annual relapse rate, a 36% decrease in disability progression and a 33% reduction in brain atrophy. Laquinimod appeared to be safe and well tolerated with few adverse events.
Further clinical trials
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BRAVO (Laquinimod Double Blind Placebo Controlled Study in RRMS Patients With a Rater Blinded Reference Arm of Interferon β-1a (Avonex)
ALLEGRO extension study
BRAVO extension study
This phase III study is comparing laquinimod 0.6mg with interferon beta 1a (Avonex) and placebo over a two year period (1332 participants). Relapse rate will be the primary measure of this study.
The study is due to finish in November 2011.
Further details of this study.
Participants completing the ALLEGRO trial were given the opportunity to continue treatment in this extension study.
Estimated completion date November 2012.
Further details of this study.
Participants completing the BRAVO trial were given the opportunity to continue treatment in this extension study.
Estimated completion date June 2013.
Further details of this study.
Side effects and contraindications
Side effects reported in the study by Comi et al included increased liver enzymes levels and in one case a more serious side effect resulting from a blood clot in the vein leading from the liver.
References
- Polman C et al.
Treatment with laquinimod reduces development of active MRI lesions in relapsing MS.
Neurology 2005;64(6):987-991.
abstract - Comi G et al.
Effect of laquinimod on MRI-monitored disease activity in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study.
Lancet 2008; 371:2085-2092
abstract - Comi G, Abramsky O, Arbizu T, et al.
Oral laquinimod in patients with relapsing-remitting multiple sclerosis: 36-week double-blind active extension of the multi-centre, randomized, double-blind, parallel-group placebo-controlled study.
Mult Scler. 2010 Nov;16(11):1360-6.
abstract