For a study, it was determined that there were currently no authorized therapies for pantothenate kinase-associated neurodegeneration (PKAN). The Fosmetpantotenate Replacement Therapy pivotal study investigated whether fosmetpantotenate medication improves PKAN symptoms and slows disease progression. Over a 24-week double-blind period, this randomized, double-blind, placebo-controlled multicenter research compared fosmetpantotenate, 300 mg oral dosage three times a day, to placebo. Patients with pathogenic PANK2 mutations, aged 6 to 65 years, with a PKAN-Activities of Daily Living (PKAN-ADL) score of 6 were recruited. Patients were randomly assigned to active (fosmetpantotenate) or placebo medication based on their weight and age. In PKAN-ADL, the primary effectiveness outcome was changed from baseline at week 24.

About 84 participants were randomized between July 23, 2017, and December 18, 2018 (fosmetpantotenate: n=41; placebo: n=43); all 84 patients were included in the analysis. Nearly 6 patients in the placebo group stopped taking their medication; two experienced increasing dystonia, two had poor compliance, and two died of PKAN sequelae (aspiration during feeding and disease progression with respiratory failure, respectively). At baseline, the PKAN-ADL mean (standard deviation) scores for the fosmetpantotenate and placebo groups were 28.2 (11.4) and 27.4 (11.5), respectively, and at week 24, they were 26.9 (12.5) and 24.5 (11.8), respectively. At week 24, the difference between fosmetpantotenate and placebo in the least square mean (95% CI) was -0.09 (-1.69 to 1.51; P=0.9115). Treatment-emergent severe adverse events were equally common in the fosmetpantotenate (8/41; 19.5%) and placebo (6/43; 14.0%) groups.

Treatment with fosmetpantotenate was safe, however, it did not improve function in PKAN patients as measured by the PKAN-ADL.