PhaseOut DMD (NCT02858362) aims to provide proof-of-concept for ezutromid through measuring certain endpoints related to muscle structure, health and function. The trial could potentially provide valuable insight into utrophin modulation as a potential disease-modifying treatment for DMD, regardless of the underlying dystrophin mutation.
DMD is a progressive muscle-wasting disease caused by genetic mutations in the gene that encodes dystrophin, a protein crucial to the healthy functioning of muscles. Utrophin protein is functionally and structurally similar to dystrophin.
In previous studies, the continued expression of utrophin was shown to improve muscle performance. Summit is now investigating the potential of this approach to slow or even stop the progression of DMD. Utrophin modulation may also complement other therapeutic approaches for DMD.
Ezutromid, Summit’s lead utrophin modulator, is an orally administered, small molecule that has been granted orphan drug status by both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The FDA has also granted ezutromid its fast-track and rare pediatric disease designation status.
In the Phase 2 trial, Summit enrolled 40 patients in the United States and Great Britain. As part of the 48-week trial, each patient undergoes one biopsy at baseline and another at either 24 or 48 weeks. The British pharmaceutical firm expects a report of the 24-week biopsy results from about 20 patients during the first quarter of 2018, as well as a report of 24-week magnetic resonance imaging (MRI) and functional data from all 40 patients. It expects top-line data by the third quarter of 2018.
“Completing enrollment in PhaseOut DMD is a major step in the development of ezutromid as we seek to understand if this utrophin modulator has positive effects on muscle structure leading to changes in muscle health and function in patients with DMD,” David Roblin, Summit’s chief operating officer and president of research and development, said in a press release. “Utrophin modulation has potential as a universal treatment option for patients with DMD.”
With the dosing of the trial’s last patient, Summit also triggered a $22 million milestone payment, as part of the company’s license and collaboration agreement with Sarepta Therapeutics of Cambridge, Massachusetts.