Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, hereditary neuromuscular disease characterized by muscle atrophy, weakness, contraction fasciculation, and bulbar involvement. Although the causative gene, androgen receptor, has been identified, the development of novel therapeutics for SBMA is incomplete. In this study, the efficacy and safety of leuprorelin acetate administration for patients with SBMA, using the pooled data of two randomized-controlled trials, was studied.
Two randomized double-blinded studies (JASMITT-06DB and JASMITT-11DB) were done as multicentric, investigator-initiated clinical trials in Japan. In both studies, eligible patients were randomly assigned 1:1 to receive leuprorelin acetate administration once per 12 weeks for 48 weeks. The primary endpoint was the longitudinal change of pharyngeal barium residues from the baseline data measured with videofluorographic swallowing analyses. The pooled analysis plan was decided upon after the 06B study was finished and before the 11DB study began.
The primary endpoint difference between the leuprorelin group and the placebo group was pharyngeal barium residue after initial swallowing, − 4.12% (95% CI, − 8.40–0.15; p = 0.058). The primary endpoint of this study does not reach significant results, although inter-group differences of pharyngeal barium residues after the initial swallowing indicated that leuprorelin acetate may be effective at each assessment point in both study groups.
The efficacy of leuprorelin acetate for patients with SBMA was statistically similar in two randomized-controlled trials, and suggested that leuprorelin acetate may be effective and safe. Further investigations are needed to clarify the promising efficacy of the drug.
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This study is funded by Large Scale Clinical Trial Network Project, which is subsidised by the Japan Ministry of Health, Labour and Welfare and supported by Health and Labour Sciences Research Grants, Japan. Study drugs were provided by Takeda Pharmaceuticals. We thank all patients and their families for participating in this study. JASMITT study group: Principle investigator in 06 DB trial, H Sasaki, M Aoki, I Nakano, S Ito, H Mizusawa, To Yamamoto, K Hasegawa, H Miyajima, G Sobue, N Kanda, K Nakajima, A tsujino, M Uchino, Principle investigator in 11DB trial, M Morita, K Kanai, Ta Yamamoto, H Mizusawa, To Yamamoto, and G Sobue.
Conflicts of interest
MK and GS have received honoraria from Takeda Pharmaceuticals. All other authors have no conflicts of interest.
Members of the group “JASMITT study group” are listed in Acknowledgements section.
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Hashizume, A., Katsuno, M., Suzuki, K. et al. Efficacy and safety of leuprorelin acetate for subjects with spinal and bulbar muscular atrophy: pooled analyses of two randomized-controlled trials. J Neurol 266, 1211–1221 (2019). https://doi.org/10.1007/s00415-019-09251-x
- Spinal and bulbar muscular atrophy
- Clinical trial
- Leuprorelin acetate
- Motor neuron disease
- Disease-modifying therapy