OBJECTIVES : To describe the landscape of DMD therapeutic development and critically explore the reasons for compound attrition in the different stages of drug development, from phase 1 to phase 4.

METHODS : All DMD clinical trials registered in the WHO International Clinical Trials Search Portal, from inception to Dec 2020 were screened and analyzed. Two authors independently selected and extracted data. Success rate in a trial phase was calculated as the number of compounds that progressed to the next trial phase divided by the number of compounds in that phase. The overall success rate was calculated as the ratio between the number of compounds that receive regulatory approval and the total number of compounds.

RESULTS : Two eighty-five trials assessing 86 compounds and sixty-four non-pharmacological interventions (devices and cell therapies) were identified. One trial was identified under Phase 0. Ninety-one (31.9%) were phase 1 trials, 103 (36.1%) phase 2, 63 (22.1%) phase 3, and 10 (3.5%) phase 4. One hundred and fifty-two trials (53.3%) received industry sponsorship. The most frequently studied compounds were Ataluren, Drisapersen, Eteplirsen and Tadalafil. The success rate was 41 % from phase 1 to phase 2, 28.3% from phase 2 to phase 3, and 26.6% from phase 3 and 4 to approval. The overall success rate was 4.6%.

CONCLUSIONS : Although DMD is a rare condition, 285 trials were identified in a comprehensive clinical trial registry. We found a very low trial success rate. There is a significant gap between drug discovery and development success rates that warrants improvement and careful appraisal of this life-threatening disease.