Laquinimod, the experimental multiple sclerosis (MS) treatment, is generally well-tolerated but produces only nominally significant effects on clinical relapses and magnetic resonance imaging (MRI) outcomes, according to the results of the CONCERTO clinical trial that aimed to evaluate the safety, efficacy, and tolerability of the treatment in patients with relapsing-remitting MS (RRMS).
Laquinimod is a novel small molecule for the treatment of MS that targets the adaptive immune response by selectively activating the aryl hydrocarbon receptor.
Studies in animal models have shown that laquinimod can decrease microglial and astrocytic reactivity and increase levels of brain-derived neurotrophic factor (BDNF).
Two previous phase 3 clinical trials showed that 0.6 mg of laquinimod had a moderate effect on relapse rates and MRI endpoints, compared to placebo.
Read more about multiple sclerosis treatment
In the CONCERTO trial, 2199 patients with RRMS, aged 18 to 55 years, were treated with either 0.6 mg or 1.2 mg per day of laquinimod or a placebo for a maximum of 2 years. However, the 1.2 mg dose was discontinued due to cardiovascular events in January 2016.
The primary endpoint of the trial was the time to disease progression confirmed after at least 3 months of treatment.
In a paper reporting the trial results in the Multiple Sclerosis Journal, Giancarlo Comi, MD, and his coauthors stated, “CONCERTO did not meet the primary endpoint.” They added, “Secondary endpoint P values were nominal and non-inferential.”
The results also demonstrated that 0.6 mg of laquinimod was associated with a 40% reduction in percent brain volume change from baseline at 15 months, compared to placebo. The times to first relapse and annualized relapse rate were also lower.
The researchers noted that laquinimod likely has a unique mechanism of action and biological effect on immune cells that are not available in the RRMS therapeutic landscape. However, they concluded that even though the study confirmed the efficacy of laquinimod in preventing the accumulation of irreversible nervous tissue damage, these positive effects were not associated with a significant risk reduction in confirmed disability progression.
Comi G, Dadon Y, Sasson N, et al. CONCERTO: a randomized, placebo-controlled trial of oral laquinimod in relapsing-remitting multiple sclerosis. Mult Scler. Published online August 11, 2021. doi:10.1177/13524585211032803
The efficacy, safety, and tolerability of laquinimod in participants with relapsing remitting multiple sclerosis (RRMS) (CONCERTO). ClinicalTrials.gov. October 16, 2012. Updated May 4, 2020. Accessed August 12, 2021.