Despite Entrada Therapeutics' efforts to persuade the FDA with additional information, the regulatory agency has rejected the company's attempts to lift the nearly yearlong clinical hold on its leading Duchenne muscular dystrophy (DMD) candidate.
The drug, an endosomal escape vehicle-conjugated phosphorodiamidate morpholino oligomer called ENTR-601-44, was placed on hold by the agency back in December 2022 while it asked the biotech to gather “additional information.” Entrada today revealed that to meet this request, it had submitted information to the FDA that helped get a phase 1 trial of ENTR-601-44 off the ground in the U.K. in September.
Clearly, the FDA is less persuadable than its British equivalents, as the agency informed the company that it has “declined to lift the clinical hold,” Entrada said today.
“We are disappointed that the U.S. clinical hold has not been lifted, especially given the strength of the data package submitted to the FDA,” Entrada CEO Dipal Doshi said in the release. “We will re-engage the FDA to discuss next steps in due course.”
The roadblock in the U.S. hasn’t stopped the company’s ambitions to develop ENTR-601-44 as a DMD treatment for people with exon 44 skippable mutations elsewhere. The first and second cohorts of healthy volunteers in the phase 1 study in the U.K. have now been dosed, and a readout is expected in the second half of 2024, Entrada pointed out in this morning’s release.
“In parallel with the phase 1 clinical trial, we continue to plan for the global development of ENTR-601-44 which will include clinical trials in patients with Duchenne who are exon 44 skipping amenable,” Doshi said.
Entrada also has plans to get two other prospective DMD treatments into the clinic in coming years: ENTR-601-45 for patients who are exon 45 skipping amenable and ENTR-601-50 for those who are exon 50 skipping amenable.
Just weeks before the FDA’s hold was initiated last year, Vertex paid Entrada $224 million upfront for a preclinical candidate for another muscle disorder called myotonic dystrophy type 1.