FDA Removes Hold on Duchenne Muscular Dystrophy Drug
After two years the FDA has lifted the clinical hold on Entrada Therapeutics’ Duchenne muscular dystrophy drug.
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Following a more than two-year-long hold, Entrada Therapeutics can get its Duchenne muscular dystrophy (DMD) candidate back on track. The company announced on Monday that the US Food and Drug Administration (FDA) had lifted its clinical hold on ENTR-601-44, which is set to enter a Phase 1b study in the US in 2026.
ENTR-601-44 is an investigational therapy for the potential treatment of people living with DMD who are exon 44 skipping amenable. The therapy is being evaluated for its potential to “skip” over the faulty section of the RNA transcript for dystrophin and allow for the translation of a slightly shortened but still functional form of the protein. The drug utilizes the company's Endosomal Escape Vehicle (EEV™) technology capable of delivering therapeutic agent-conjugated cargo intracellularly, in this instance that cargo is a phosphorodiamidate morpholino oligomer.
What is Duchenne muscular dystrophy (DMD)?
DMD is a rare disease that is caused by mutations in the DMD gene, which lead to inadequate dystrophin production. Lack of functional dystrophin leads to progressive loss of muscle function throughout the body, which can cause heart or respiratory complications that contribute to high mortality rates.
The FDA placed ENTR-601-44 on clinical hold in late 2022, preventing the company from starting a planned healthy volunteer study in the US. The FDA placed the hold while it asked the biotech to gather “additional information.”
Now, the wait is finally over, with Entrada confirming it has received the green light from the FDA to launch the ELEVATE-44-102 study.
The randomized, double-blind placebo-controlled Phase 1b study will evaluate the safety and tolerability of ENTR-601-44 in approximately 32 non-ambulatory and ambulatory adult patients with DMD who are exon 44 skipping amenable.
Despite the initial roadblock in the US, the drug has already been studied in healthy volunteers in the UK with no drug-related adverse events reported. The UK Medicines and Healthcare Products Regulatory Agency has now authorized a Phase 1/2 clinical study of the drug which is expected to begin in the second quarter of this year.
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Subscribe for FREE“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 Therapeutics said in a press release.
DMD is a rare disease with an estimated prevalence of 5.3 cases per 100,000 males. While there is currently no cure for DMD, several treatment options focus on improving the quality of life and slowing the progression of symptoms associated with the disease. Exon skipping agents have emerged as promising candidates with clinical advantages over traditional therapies, such as corticosteroids.
Entrada Therapeutics is not the only company pursuing exon 44 skipping therapies for DMD. NS Pharma, a subsidiary of Nippon Shinyaku, is conducting a Phase 2 study of NS-089/NCNP-02, an antisense oligonucleotide expected to be a therapeutic drug for Duchenne patients who have dystrophin gene mutations amenable to exon 44 skipping.
Other therapies under investigation include ELEVIDYS, an adeno-associated virus-based gene therapy for the treatment of ambulatory pediatric patients aged 4 through 5 years with DMD and confirmed mutation in the DMD gene. The therapy developed by Sarepta Therapeutics received FDA accelerated approval in 2023.
