G.O.27

SA-ER was investigated in a Phase 2 randomized, double-blind, placebo-controlled 48week study evaluating dose, PK and clinical efficacy. 47 subjects were originally enrolled and randomized to receive either placebo, 3g or 6g of SA-ER/day. After 24weeks, placebo patients crossed to either 3g or 6g dose/day for an additional 24weeks. After a variable extension period at 6g, all 46 continuing subjects and 13 newly enrolled naive subjects were treated with a 50:50 combination of SA-ER plus SA at a dose of12 g per day to assess whether a higher dose and serum SA level would have better efficacy. Study assessments included PK, muscle strength by hand-held dynamometry [(HHD) composites of upper extremity (UEC), lower extremity (LEC)], other clinical endpoints, patient reported outcomes (PRO) and safety. Muscle strength assessments by HHD at 24weeks showed that the UEC in the 6g group was significantly greater than placebo (+2.33kg, p =0.04). At 48weeks after placebo subjects crossed over, the combined 6g group was significantly superior than the combined 3g group (+3.44kg, p =0.0033) and the difference was larger in the predefined >200m baseline 6MWT walking group (+4.70kg, p ; p =0.087), mobility ( p =0.087) and UE scores ( p =0.096) in the combined 6g vs. the combined 3g group by ANCOVA. Clinical endpoints related to walking (e.g. 6 MWT) did not reveal significant changes. The impact of an increased dose of 12g in the 46 continuing and in 13 naive HIBM subjects will be presented. SA-ER appeared to be well tolerated with no serious adverse events observed at 3 or 6g/day. These data suggest that the SA-ER 6g dose is having a clinically meaningful effect stabilizing UEC muscle strength.