Dystrophin remains top DMD surrogate endpoint, but other metrics on the rise
Thanks to flaws in PTC Therapeutics Inc.’s trials, the recent FDA advisory committee meeting to discuss Translarna ataluren did nothing to clarify what level of dystrophin expression would be necessary to support an accelerated approval for Duchenne muscular dystrophy.
The chance to determine what level of dystrophin expression will correlate with improvements in function will likely come in 2019, when Sarepta Therapeutics Inc. reports data from two Phase III studies for three of its exon-skipping compounds.
The Phase III ESSENCE trial is testing golodirsen, a phosphorodiamidate morpholino oligomer (PMO) targeting exon 53, and casimersen, a PMO targeting exon 45. Sarepta also expects data from the confirmatory trial of Exondys 51 eteplirsen.
Meanwhile, several companies and academic groups are using experimental surrogate endpoints that could provide supportive data for therapies that work by other mechanisms, and for dystrophin-inducing therapies when it is unclear whether the quantity of dystrophin a drug candidate produces is reasonably likely to predict a clinical benefit.
Once qualified by regulators, these new endpoints could join or replace dystrophin as acceptable primary surrogate endpoints.
On Oct. 4, Catabasis Pharmaceuticals Inc. presented data on one of these endpoints that correlated with function. The Phase II MoveDMD trial showed edasalonexent significantly improved muscle inflammation as measured by MRI of lower leg muscle (p<0.05). The therapy also