Summit Therapeutics unveils encouraging early data for Duchenne drug

Duchenne muscular dystrophy
Summit's drug, ezutromid, is designed to raise utrophin levels to make up for the lack of dystrophin in patients with Duchenne muscular dystrophy. (CDC)

Summit Therapeutics reported 24-week data showing its Duchenne muscular dystrophy drug ezutromid boosted utrophin levels and decreased muscle damage in a phase 2 trial.

DMD is caused by mutations in the dystrophin gene, which codes for a protein of the same name. Without this stabilizing protein, muscle fibers eventually weaken and die. There is no cure for DMD and current therapies focus on managing the disease, which includes maintaining comfort and muscle function.

Summit’s ezutromid is designed to boost levels of the protein utrophin to compensate for the lack of dystrophin in patients with DMD. The approach has been shown to ward off disease progression in preclinical models. If it is successful in humans, ezutromid could become a universal, disease-modifying treatment for DMD, said Kay Davies FRS, a professor at the University of Oxford and a cofounder of Summit, in a statement.

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At 24 weeks, treatment with ezutromid led to a “meaningful” reduction in muscle damage, measured in a 23% decrease in mean developmental myosin—a biomarker of muscle damage—in a muscle biopsy compared to baseline. Two-thirds, or 14 out of 22, patients experienced a decrease in developmental myosin. And the mean level of utrophin jumped 7% compared to baseline.

“The significant reduction in muscle damage coupled with the increase in utrophin expression […] is very encouraging as it suggests ezutromid may slow the relentless cycle of muscle fibre degeneration and regeneration that is a hallmark of DMD,” said Francesco Muntoni, director of the Dubowitz Neuromuscular Centre, at the UCL Institute of Child Health and Great Ormond Street Hospital for Children in London, in the statement. “These favourable interim results are certainly a step forward in the development of utrophin modulation as a treatment approach for this fatal disease in all patients with DMD.”

Summit expects to report topline data in the third quarter.

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In October 2016, Summit inked a licensing deal with Sarepta, which bagged an FDA nod for Exondys 51, a Duchenne drug indicated for a narrow band of patients.

Under the agreement, potentially worth more than $584 million, Summit handed Sarepta the rights to its utrophin modulator pipeline in Europe, Turkey and the Commonwealth of Independent States. Sarepta also has the option to license the Latin American rights to the assets.

In addition to Exondys 51, which is indicated for about 13% of patients with DMD whose dystrophin mutation is amenable to exon 51 skipping, Sarepta is working on the next-generation drug golodirsen. The Summit deal, as well as one with France’s Genetheon, are part of Sarepta’s quest to bring forth a broader treatment for DMD.