Santhera flunks DMD phase 3, prompting restructuring and withdrawal of approval application 

Santhera Pharmaceuticals has stopped a phase 3 trial of Duchenne muscular dystrophy (DMD) drug idebenone after it failed an interim analysis. The setback prompted Santhera to outline plans to pull a filing for approval and restructure around a second asset that it secured global rights to last month.

Last year, Santhera refiled for European Medicines Agency (EMA) approval of idebenone on the strength of data from a phase 3 trial that linked the synthetic short-chain benzoquinone to a slowdown in the loss of respiratory function. The application followed an earlier, drawn-out effort to get idebenone to market in DMD that ended with an EMA rejection in 2017 and a failed appeal early the following year.

Santhera initiated a second phase 3 trial, SIDEROS, to support a filing for approval in the U.S.. That trial has brought the whole idebenone program crashing down and forced Santhera to shift its focus.

SIDEROS randomized 255 DMD patients taking glucocorticoid steroids to receive idebenone tablets or placebo. The phase 3 trial was designed to show whether idebenone delays the loss of respiratory function. 

Santhera is yet to share data from the trial, but the results were bad enough to lead it to immediately cull the program. An interim analysis by the data and safety monitoring board found the study was very unlikely to succeed, leading Santhera to stop dosing in the trial and start wrapping up follow-up evaluations. The action marks the end of the global development program for idebenone.

With the trial triggering the end of Santhera’s efforts to get idebenone to market, management plans to restructure the business to reflect its new focus. Santhera is yet to share details of what that will mean for its employees but has sketched out the operations that will survive the restructuring.

The Santhera that will emerge from the restructuring will be focused on vamorolone in DMD and lonodelestat in lung diseases such as cystic fibrosis. Vamorolone, a nonhormonal steroid modulator that Santhera exercised its option on last month, is in a pivotal phase 3 trial that is due to deliver top-line data in the second quarter of 2021. Lonodelestat is in phase 1b in cystic fibrosis.

Santhera will continue preclinical work on its discovery-stage gene therapy project but the removal of idebenone from the pipeline has delayed its need for commercial capabilities. Before seeing the interim data, Santhera was gearing up to bring idebenone to market in Europe in the first quarter of 2021. 

Shares in Santhera fell more than 30% in the wake of the news.