FDA Places Clinical Hold on Entrada’s IND for Duchenne Muscular Dystrophy


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The FDA placed a clinical hold on the Investigational New Drug application for Entrada Therapeutics’ Duchenne muscular dystrophy (DMD) candidate, ENTR-601-44.  

Boston-based Entrada announced Tuesday it received a clinical hold notice from the regulatory agency. No reason was provided, but Entrada noted the FDA will provide an official letter within 30 days.  

BioSpace reached out to Entrada for additional details.

Investors responded negatively to news. Shares of Entrada Therapeutics fell more than 32% in premarket trading to $13.50. The stock closed Monday at $19.89.

ENTR-601-44, an exon 44 skipping oligonucleotide, is Entrada’s most-advanced product candidate. It was developed with the company's Endosomal Escape Vehicle (EEV) platform.

ENTR-601-44 is designed to address the underlying genetic cause of DMD by allowing muscle cells to produce functional dystrophin. Entrada estimates ENRE-601-44 will benefit 7.5% of DMD patients who are considered exon 44 skipping amenable.

Dipal Doshi, president and chief executive officer of Entrada, said the company will address the FDA’s concerns regarding the IND. Doshi noted there are no approved therapies for DMD patients with exon 44 skippable mutations.

“We are eager to resolve this hold and continue down the treatment development pathway,” he said in a brief statement.

DMD is an X-linked degenerative neuromuscular disorder that causes severe progressive muscle loss and premature death. It is estimated the disease affects one in 3,500 male births. There are approximately 30,000 DMD patients in the U.S. and EU.

DMD is associated with specific errors in the gene that codes for dystrophin, a protein that plays a key structural role in muscle fiber function. Muscles lacking dystrophin are more susceptible to damage.  

Currently, there are five therapies approved by the FDA for various forms of the muscle-wasting disorder. Three of those therapies, Emflaza, Vyondys 53 and Viltepso, were developed by Sarepta Therapeutics. Sarepta is reportedly on the cusp of adding a fourth DMD therapeutic to its portfolio.

In November, the FDA accepted Sarepta’s Biologics License Application for SRP-9001 (delandistrogene moxeparvovec), an investigational gene therapy for DMD. Sarepta is developing the gene therapy in partnership with Roche.

Other companies developing DMD therapies include REGENXBIO, PTC Therapeutics, Caritas Therapeutics and Pfizer.

The clinical hold announcement comes weeks after Entrada and Vertex Pharmaceuticals forged a collaboration to develop intracellular EEV therapeutics. The partnership centers on Entrada’s pre-clinical myotonic dystrophy type 1 (DM1) therapeutic, ENTR-701, which is designed to address the underlying cause of the disease.

Vertex is also developing a gene therapy for DMD. In 2019, the company acquired Exonics Therapeutics, which was developing CRISPR-Cas9-based therapies that can correct exon mutations.

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