Conference Coverage

Laquinimod may not improve motor function in Huntington’s disease



– Laquinimod appears not to improve motor function or clinical outcomes in patients with Huntington’s disease, according to a study presented at the annual meeting of the American Academy of Neurology. However, the drug reduced brain volume loss in the caudate and other regions.

Laquinimod is an investigational immunomodulatory drug that prevents inflammation and neurodegeneration in the CNS. The treatment was studied as a therapy for multiple sclerosis (MS), but development for this indication has been stopped. Researchers have observed that laquinimod modulates inflammatory pathways that are involved in Huntington’s disease pathology.

Ralf Reilmann, MD, PhD, founder of the George Huntington Institute and chair of the Huntington unit at the University of Münster (Germany), and colleagues conducted the phase 2 LEGATO-HD study at 48 sites in 10 countries to examine the efficacy and safety of laquinimod in patients with early Huntington’s disease. Participants were randomized in double-blind fashion to daily placebo or 0.5-mg, 1.0-mg, or 1.5-mg doses of laquinimod for 52 weeks. After the initiation of this trial, studies of the drug in MS indicated that the 1.5-mg dose was associated with cardiovascular risks, and Dr. Reilmann and his colleagues discontinued the 1.5-mg arm of their trial as a precaution.

The primary endpoint of LEGATO-HD was the change from baseline in the Unified Huntington’s Disease Rating Scale (UHDRS)–Total Motor Score (TMS). The secondary endpoint was the percent change in caudate volume at week 52 for the 1.0-mg dose group, compared with controls. The investigators also examined exploratory endpoints such as changes in MRI volume measures and Quantitative Motor, Clinician Interview-Based Impression of Change plus caregiver input, UHDRS–Total Functional Capacity and UHDRS–Functional Assessment scores. Adverse event reporting and clinical and laboratory examinations constituted the safety measures.

Dr. Reilmann and colleagues found no difference between the treated patients and controls in UHDRS-TMS. However, they did observe less caudate volume loss in the laquinimod group, compared with controls. All MRI exploratory measures also favored laquinimod. The researchers found no treatment effects of laquinimod in rater-dependent clinical outcome measures. Laquinimod was well tolerated, and the study yielded no new safety findings.

Dr. Reilmann has received research support from Teva, which supported the LEGATO-HD trial and in 2018 sold development and commercial rights for laquinimod to Active Biotech. He has received research support from a variety of other pharmaceutical companies and organizations, including the CHDI Foundation and the European Huntington Disease Network.

SOURCE: Reilmann R et al. AAN 2019, Abstract S16.007.

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