To evaluate the clinical implications of MiToS in FORTITUDE-ALS, a phase 2 study of reldesemtiv in ALS.

MiToS stages are based upon loss of independence in swallowing, walking/self-care, communicating, and breathing.

Patients were classified into MiToS stages and time of transitioning from baseline stage to later stages (TTLS) and the proportion of patients who transitioned from baseline stage to later stages (PPLS) were calculated.

TTLS [n/average days (SD)] was from stage 0 to stage 1 and 2[reldesemtiv: stage 1: 5/17.2(6.65), stage 2: 2/71.5(20.51): placebo: stage 1: 3/15.3(0.58), stage 2: 2/16.0(1.41)], stage 1 to stage 2 and 3[reldesemtiv: stage 2: 40/43.1(28.39), stage 3: 11/61.5(27.65): placebo: stage 2: 16/40.8(26.09), stage 3: 4/36.0(32.63)], stage 2 to stage 3 and 4[reldesemtiv: stage 3: 37/38.0(28.17), stage 4: 8/62.3(24.71): placebo: stage 3: 11/36.2(26.22), stage 4: 5/57.8(40.01)] and stage 3 to stage 4 [reldesemtiv: stage 4: 24/44.4(26.52): placebo: stage 4: 10/47.7(28.18)].

PPLS[n(%)] who transitioned from stage 0 to stage 1 and 2 were [reldesemtiv:4(44.4%), placebo:5(83.3%)],[reldesemtiv:1(11.1%), placebo:0(0.0%)]; stage 1 to stage 2,3,4 and 5 [reldesemtiv:32(25.4%), placebo:8(18.2%],[reldesemtiv:6(4.8%), placebo:3(6.8%)],[reldesemtiv:2(1.6%), placebo:0(0.0%)],[reldesemtiv:0(0.0%), placebo:1(2.3%)]; stage 2 to stage 3 and 4[reldesemtiv:27(30.7%), placebo:8(28.6%],[reldesemtiv:6(6.8%), placebo:3(10.7%)] and stage 3 to stage 4[reldesemtiv:15(24.2%), placebo:9(45.%)]. Overall the rate of patients progressed to a later stage in the reldesemtiv and placebo were 30.5% (93/305) and 36.6% (37/101) respectively.

Reldesemtiv group had longer transition time and smaller transition rate compared to placebo.

This post-hoc analysis showed TTLS and PPLS using MiToS staging in a 12-week study of reldesemtiv and suggests it may be a useful outcome measure to use in ALS trials as a measure of treatment effect between groups.