Myasthenia Gravis generalised

December 3, 2012

Cytokinetics issued results from a phase IIa trial of tirasemtiv for the treatment of generalized myasthenia gravis (MG). This double-blind, randomized, three-period crossover, placebo-controlled study, CY 4023, enrolled 32 patients with generalized MG. Subjects received separate, single doses of tirasemtiv 250mg, tirasemtiv 500mg and placebo in random order approximately one week apart. Since the study was a hypothesis-generating trial, no single primary efficacy endpoint was pre-specified. Results showed that six hours after dosing, improvements (decreases) in the Quantitative MG score (QMG) were related to the tirasemtiv dose in a statistical significant manner (-0.49 QMG points per 250mg; p=0.02). Decreases in certain components of the QMG and their relationships to dose were statistically significant or borderline significant. Also at six hours after dosing, increases in the percent predicted forced vital capacity were statistically significantly related to the dose level of tirasemtiv (2.2% per 250mg; p=0.04), as were the individual comparisons of each dose level of tirasemtiv versus placebo. The drug was well tolerated. The most frequent adverse event was dizziness. Cytokinetics has initiated a phase IIb trial of tirasemtiv in patients with ALS. Tirasemtiv has also been granted Orphan Drug designation and Fast Track status by the FDA.

September 19, 2011

Alexion released results from a phase II trial of eculizumab for severe and refractory generalized myasthenia gravis. This randomized, double-blind, placebo-controlled, cross-over study enrolled 14 subjects who had moderate to severe muscle weakness despite treatment with immunosuppressants. The subjects were randomized to eculizumab in the first treatment period (16 weeks) followed by placebo in the second treatment period (16 weeks), or the reverse treatment sequence. The primary endpoint was to demonstrate the clinical benefit of eculizumab in improving Quantitative Myasthenia Gravis disease severity score (QMG score) relative to placebo. In the first treatment period 86% of the eculizumab arm compared to 57% of the placebo arm achieved a three-point reduction in their QMG score after 16 weeks of treatment. This improvement was achieved more rapidly for eculizumab compared to placebo (p≡0.078). The overall change in mean QMG total score from baseline to the last visit of the study was significantly improved more than four points with eculizumab compared to placebo (p≡0.0144). Eculizumab appeared well-tolerated.

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