Laquinimod does not improve motor scores in Huntington disease

The immunomodulator laquinimod failed to meet its primary endpoint of improving rater-dependent clinical outcomes at 1 year in patients with early Huntington disease in the LEGATO-HD study. It did, however, result in reduced volume loss in the caudate nucleus and other brain regions [1].

Laquinimod had previously been shown to modulate CNS-resident inflammatory pathways involved in the pathology of Huntington disease. The 52-week phase 2 study LEGATO-HD compared once daily 0.5, 1.0, and 1.5 mg laquinimod to placebo. The 1.5 mg arm was discontinued in 2016 as a precautionary safety measure, due to cardiovascular safety concerns in MS studies with laquinimod 1.2 and 1.5 mg doses. The study's primary endpoint was change in the Unified Huntington’s Disease Rating Scale Total Motor Score (UHDRS-TMS).

There was no significant change from baseline in UHDRS-TMS (P=0.49). The secondary endpoint of percent change in caudate volume loss at week 52 was met (P=0.0002). There were also treatment effect differences between the laquinimod and placebo group for all MRI exploratory measures. No treatment effects were observed in rater-dependent clinical outcome measures. A treatment effect was suggested by certain Quantitative (Q)-Motor rater-independent assessments, e.g. of tap speed inter-onset-interval of the hands. Laquinimod was well-tolerated and there were no new safety signals.

1. Reilmann R, et al. AAN 2019, S16.007.



Posted on 30 July, 201925 March, 2024