Entrada Therapeutics On Track For New DMD Study in the U.K.

There is a significant unmet medical need for people living with Duchenne muscular dystrophy (DMD), which is why Entrada Therapeutics has come up with a new study hoping to bring some help.

The company announced it has been cleared in the U.K. to start a Phase 1/2 clinical trial of ENTR-601-44, at increasing doses, in patients with a mutation in the DMD-related gene amenable to exon 44 skipping.

ELEVATE-44-201 is a global, two-part, randomized, double-blind placebo-controlled Phase 1/2 study evaluating the safety, tolerability and effectiveness of ENTR-601-44 in approximately 24 ambulatory patients with DMD who are exon 44 skipping amenable.

Dipal Doshi

“Part A is a multiple ascending dose study designed to evaluate the safety, pharmacokinetics and pharmacodynamics, including exon skipping and dystrophin production,” Dipal Doshi, Entrada Therapeutics’ CEO, told MHE. Dosing will be administered every six weeks, with the planned doses across three cohorts anticipated to range from 6 milligrams per kilogram of bodyweight up to 18 milligrams,

Part B of the study is designed to further evaluate the optimal dose established in Part A for safety and efficacy, including patient reported outcomes and quality of life measures.

Entrada, a Boston-based company is on track to initiate ELEVATE-44-201 in second quarter of this year.

the FDA put a clinical hold on Entrada’s ENTR-601-44 trials in 2022, and the company announced in 2023 that it had been extended.

“In anticipation of regulatory clearance, our clinical development, clinical operations and patient advocacy teams have been working diligently to prepare sites and clinical study materials to ensure an efficient start to this study,” Doshi said. “The approval in the UK is part of our global strategy and regulatory discussions are ongoing in additional geographies.”

The Medicines and Healthcare Products Regulatory Agency (MHRA) authorization follows the completion of a Phase 1 clinical study that evaluated the safety and tolerability of a single dose of ENTR-601-44 in a healthy volunteer.

“This study demonstrated ENTR-601-44 was generally well-tolerated in healthy volunteers with no serious adverse events, no drug-related adverse events and no clinically significant changes or trends noted in vital signs, electrocardiograms, physical exams or laboratory assessments,” Doshi said. “The study also demonstrated significant plasma concentration, muscle concentration and exon skipping.”

Information about ELEVATE-44-201 will be available on multiple public clinical trial registries, including Clinicaltrials.gov, the UK ISRCTN, and the EU Clinical Trials Information System in the coming months.

“Our team has also been actively preparing patient focus materials, including a trial website, that will go live in conjunction with enrollment,” Doshi said. “Additionally, at Entrada, we work shoulder to shoulder with patient advocacy organizations—constantly uncovering ways that we can improve treatments and expand access faster than by working alone.”

DMD is a genetic disease caused by mutations of the dystrophin gene, located on chromosome Xp21. Mutations in the dystrophin gene cause diseases known as dystrophinopathies, which which include DMD and less well-known Becker muscular dystrophy. The dystrophin gene mutations result in a limited production of the dystrophin protein, which is critical to healthy muscle tissue. The disease usually becomes apparent when children are toddlers. Progressive weakness and muscle wasting caused by degenerating muscle fibers begins in the upper legs and pelvis before spreading into the upper arms.

DMD is inherited as an X-linked recessive manner, so boys are more frequently affected than girls. Research has shown a range of incidences, from 1 case per 3,500 live male births to 1 in approximately 5,000.

Entrada says on its website that there are 41,000 people in the U.S. and Europe living with the DMD.