Duchenne muscular dystrophy (DMD) is a progressive muscular disease characterized by chronic cycles of inflammatory and necrotic processes. Prostaglandin D2 (PGD2) is produced by hematopoietic PGD synthase (HPGDS), which is pathologically implicated in muscle necrosis.

A new study published in the Annals of Clinical and Translational Neurology assessed the efficacy and safety of the novel selective HPGDS inhibitor, TAS-205, with exploratory measures in male DMD patients aged ≥5 years.

This was a randomized, double-blinded, placebo-controlled, early phase-2 trial that enrolled 36 patients—of whom 35 were analyzed for safety. Patients were randomized in the ratio 1:1:1 to receive either low-dose TAS-205 (6.67-13.33 mg/kg/dose); high-dose TAS-205 (13.33-26.67 mg/kg/dose); or placebo. The primary endpoint was change from baseline in a 6-minute walking distance (6MWD) at week-24.

The findings showed that the mean (standard error) changes from baseline to week-24 in 6MWD were -17.0 (17.6) m in the placebo group; -3.5 (20.3) m in the TAS-205 low-dose group; and -7.5 (11.2) m in the TAS-205 high-dose group. The mean difference from the placebo group was 13.5 (-43.3 to 70.2) m in the TAS-205 low-dose group and 9.5 (-33.3 to 52.4) m in the TAS-205 high-dose group. No obvious differences were noted in the incidences of adverse events between the treatment groups. Additionally, no adverse drug reactions specific to TAS-205 treatment were reported.

From the results, it was inferred that the HPGDS inhibitor TAS-205 showed a favorable safety profile in DMD patients.

Source: Annals of Clinical and Translational Neurology. 2020 Feb;7(2):181-190. doi: 10.1002/acn3.50978.