ENTR-601-44 trial for DMD adults amenable to exon 44 skipping OK’d
ELEVATE-44-102 is expected to enroll about 32 adults with DMD
The U.S. Food and Drug Administration (FDA) has given Entrada Therapeutics permission to launch a Phase 1b clinical trial to test ENTR-601-44, the company’s experimental exon-skipping therapy, in adults with Duchenne muscular dystrophy (DMD) who carry a mutation that’s amenable to exon 44 skipping.
Entrada had sought the FDA’s OK to start the trial in 2022, but the agency put the application on hold later that year. The FDA has now lifted its hold and given the go-ahead for the trial, called ELEVATE-44-102, to launch.
“Given the strength of our safety and target engagement data from our Phase 1 clinical study and the profound unmet need in adults living with Duchenne, we are pleased to have obtained FDA clearance for the ELEVATE-44-102 study,” Dipal Doshi, CEO of Entrada, said in a company press release.
ELEVATE-44-102 is expected to enroll about 32 adults with DMD who are amenable to exon 44 skipping, according to the company. The study is expected to include patients who can walk and those who can’t.
“The study will help assess the potential of ENTR-601-44 in both nonambulatory and ambulatory adult patients who are unfortunately often left out of clinical studies due to the advanced stage of their disease,” Doshi said. “Nearly half of those living with Duchenne who are amenable to exon 44 skipping are adults. ELEVATE-44-102 will provide clinical experience from this important population for our growing data package in support of what we believe will be a best-in-class therapy.”
What is ENTR-601-44 expected to do in DMD?
The study’s participants will be randomly assigned to ENTR-601-44, given every six weeks at doses ranging from 0.16 mg/kg up to 1.28 mg/kg, or a placebo. Its main goal will be to assess the therapy’s safety and tolerability.
Entrada said enrollment should start in the first half of 2026. Once the placebo-controlled part of the trial is done, participants may have the option to continue into an open-label extension where they all could receive long-term treatment with ENTR-601-44.
DMD is caused by mutations in the DMD gene, which provides instructions to make dystrophin, a protein that normally helps prevent muscle damage. In DMD, mutations in the DMD gene lead to virtually no dystrophin being made, resulting in muscle cells accumulating damage over time, driving disease symptoms.
Like other protein-coding genes, the DMD gene is composed of sections called exons, many of which come together to form the gene, not unlike how different words are put together to make a sentence. The goal of exon-skipping therapy is to get cells to skip over one or more specific exons when the gene is used to make dystrophin, thus letting cells make a shorter but functional version of the protein that can help prevent muscle damage.
ENTR-601-44 is intended to facilitate skipping exon 44 of the DMD gene. The therapy has been tested in a Phase 1 study of healthy volunteers and the results indicated ENTR-601-44 promoted exon skipping as designed, according to Entrada.
Clearance for the U.S. study comes a few weeks after regulators in the U.K. cleared a Phase 1/2 study called ELEVATE-44-201, which plans to test ENTR-601-44 in DMD patients who can walk and are amenable to exon 44 skipping.
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