#AANAM – Laquinimod Reduces Brain Atrophy in Early Huntington’s, Study Shows

Experimental immunotherapy laquinimod reduced brain atrophy in the caudate nucleus, one of the most affected brain areas in Huntington’s disease, and other cerebral regions but it did not improve motor function in recently diagnosed patients, LEGATO-HD study findings show.

Results from the trial were recently discussed at the 2019 American Academy of Neurology’s (AAN) Annual Meeting in Philadelphia. The oral presentation, “The Efficacy and Safety Results of Laquinimod as a Treatment for Huntington Disease (LEGATO-HD),” was given by Ralf Reilmann, MD, PhD, global coordinating principal investigator of the study.

Laquinimod is an oral active modulator of the immune system that works by changing immune cells’ behavior in order to reduce inflammation in the central nervous system. The therapy was developed by Active Biotech and Teva Pharmaceutical Industries.

Previous studies have demonstrated that the candidate molecule could regulate brain-related inflammatory pathways involved in the underlying mechanisms of Huntington’s disease.

The Phase 2 LEGATO-HD study (NCT02215616) was designed to evaluate laquinimod’s efficacy and safety in patients with early Huntington’s disease. Researchers evaluated the impact of treatment with distinct doses of laquinimod — 0.5, 1.0, and 1.5 mg — administrated once daily for 12 months, and compared it with a placebo.

The study’s primary goal was to assess changes in patients’ motor function before and after starting the treatment, as determined by the Unified Huntington’s Disease Rating Scale Total Motor Score (UHDRS-TMS). Researchers also evaluated effects of the treatment on brain atrophy as a secondary efficacy measure.

Results from other clinical trials in multiple sclerosis raised some safety concerns about the highest tested laquinimod dose. Teva Pharmaceutical Industries subsequently decided to discontinue treatment with the 1.5 mg dose, but continued clinical development of the investigational therapy with the two other dosages.

Preliminary LEGATO-HD reports noted that laquinimod was unable to meet its primary objective of improving motor function in Huntington’s disease patients after 12 months. More recent complete analysis of the trial data confirmed that indeed the investigational immunotherapy could not effectively improve patients’ motor function, but it still had a positive effect on patients’ hand tap speed.

Further analyses also demonstrated that the percentage of volume loss in the caudate nucleus — the brain area most affected in Huntington’s — was significantly reduced in patients treated with 1.0 mg of laquinimod compared to those treated with a placebo. This suggests that the immunotherapy may hold the potential to slow down disease progression.

“While laquinimod treatment resulted in reduced volume losses in caudate and other brain regions for early Huntington’s disease patients, there was no evidence of improved rater-dependent clinical outcomes in the LEGATO-HD study,” researchers stated.

In general, the therapy was well-tolerated and found to be safe, with no additional safety concerns being detected.

The LEGATO-HD trial was sponsored by Teva in collaboration with the Huntington Study Group and the European Huntington’s Disease Network.