Despite putting up encouraging early data, Summit Therapeutics' Duchenne muscular dystrophy (DMD) drug missed its primary and secondary endpoints in a phase 2 trial, leading the biotech to drop the program and focus its energies behind its antibiotic pipeline.
Summit's shares plunged 78% in premarket trading.
DMD is caused by mutations in the dystrophin gene that stop the production of the stabilizing protein dystrophin. Without it, muscle fibers weaken and eventually die. Ezutromid is designed to treat DMD by boosting levels of utrophin to compensate for patients' missing dystrophin. Summit co-founder Kay Davies said in January that it had the potential to become a universal, disease-modifying treatment for DMD, a progressive disease that does not have a cure.
Of the 40 boys with DMD enrolled in the phase 2 trial, 38 completed it through the 48-week mark. Summit reported 24-week data in January, showing that ezutromid decreased muscle damage and increased utrophin levels—the study's secondary endpoints. But come 48 weeks, the drug did not meet these endpoints, nor did it meet the primary endpoint: the change from baseline in magnetic resonance parameters related to the leg muscles.
"These data come as a great disappointment to us and to all those living with DMD," said Summit CEO Glyn Edwards in a statement. "While we believe utrophin modulation could still have a place in the treatment of DMD, it is clear that ezutromid is not providing a benefit for patients. We therefore feel that our resources are better focussed on the development of our promising pipeline of new mechanism antibiotics."
Summit expects to start phase 3 trials testing its lead asset, ridinilazole, against C. diff infection in the first quarter of 2019. It is terminating the ezutromid program and plans to implement "cost reduction measures."
The disappointment comes nearly two years after Sarepta paid Summit $40 million up front to get the rights to ezutromid and the rest of Summit's utrophin modulator pipeline in Europe, Turkey and the Commonwealth of Independent States. Summit stood to receive up to $522 million in milestones and royalties, including $22 million upon the initiation of the phase 2 trial.
While this is a blow for Sarepta, the Duchenne-focused biotech has been on the up and up. Just last week, Sarepta presented very early data from a phase 1/2 clinical trial of a potentially curative gene therapy. Biopsies taken from the first three patients dosed with the treatment showed they had "robust levels" of microdystrophin, producing 38% of the protein compared to normal. All three patients also showed "significant decreases" in their level of serum creatine kinase, a biomarker linked to muscle damage caused by DMD. Sarepta's stock leapt 50% on the news.
Sarepta's first Duchenne drug, Exondys 51, scored FDA approval back in 2016 but is only effective in a small subset of patients whose disease is amenable to exon skipping. Sarepta is working on a number of prospects that could be more widely usable, as well as those that could become one-time, curative therapies. These include a next-generation, peptide-conjugated version of the technology Exondys 51 is based on, as well as gene therapies.