Leriglitazone not effective in slowing disease in men with adrenomyeloneuropathy

Although well-tolerated with few adverse events, treatment with leriglitazone did not slow disease progression in men with adrenomyeloneuropathy compared with placebo, per a study published in Lancet Neurology.

“Although a few drug therapies have been tested in small numbers of patients with adrenoleukodystrophy, no effective disease-modifying medication is available,” Wolfgang Köhler, MD, of the department of neurology at University of Leipzig Medical Center in Germany, and colleagues wrote.

Researchers evaluated the safety and efficacy of leriglitazone in preventing disease progression in men with adrenomyeloneuropathy by conducting the ADVANCE study, a 96-week, randomized, double-blind, placebo-controlled, phase 2/3 trial at 10 hospitals throughout Europe and the United States.

Between Dec. 8, 2017, and Oct. 16, 2018, they screened 136 individuals aged 18 to 65 years, who were ambulatory and diagnosed with adrenomyeloneuropathy but lacking gadolinium-enhancing lesions indicative of disease progression. From that cohort, 116 participants were randomly assigned on a 2:1 basis to receive daily oral suspensions of leriglitazone (starting at 150 mg, then increased or decreased between baseline and week 12 to achieve plasma concentrations of 200 g/mL per hour) or placebo.

The primary outcome of interest was change from baseline to week 96 in the distance recorded in the Six-Minute Walk Test.

Of 116 participants who were randomized, 62 of 77 receiving leriglitazone and 34 of 39 given placebo completed treatment. Researchers reported no between-group difference in the primary endpoint (mean change from baseline, leriglitazone = –27.7 m; placebo = –30.3 m; least-squares mean difference = –1.2 m; 95% CI, –22.6 to 20.2).

Further, the total distance walked in the Six-Minute Walk Test was similar between treatment groups at baseline, while mean total distance walked decreased in both groups from baseline to week 96.

Treatment emergent adverse events for leriglitazone and placebo groups were similar and included weight gain (54 of 77 vs. nine of 39 patients, respectively) and peripheral edema (49 of 77 vs. seven of 39). Serious treatment-emergent adverse events were reported in 14 of 77 patients on leriglitazone and 10 of 39 on placebo, but no deaths were reported.

“Although the primary endpoint was not met, leriglitazone showed evidence of beneficial effects on several study parameters,” Köhler and colleagues wrote. “We believe that our findings show a favorable benefit-risk profile for leriglitazone, which might offer a promising therapy for patients with adrenomyeloneuropathy and cerebral adrenoleukodystrophy.”