Entrada Therapeutics reported positive Phase 1/2 Cohort 1 data for ENTR-601-44 in Duchenne muscular dystrophy, showing favorable safety, increased dystrophin production, and statistically significant improvement in Time to Rise velocity in the ELEVATE-44-201 study (NCT07037862).
Written By: Farha Farheen, PharmD
Reviewed By: Pharmacally Editorial Team
Entrada Therapeutics reported positive topline results from Cohort 1 of the Phase 1/2 ELEVATE-44-201 study (NCT07037862) evaluating ENTR-601-44 in ambulatory patients with Duchenne muscular dystrophy (DMD) amenable to exon 44 skipping. The investigational therapy met the study’s primary objective, demonstrating favorable safety and tolerability alongside early functional improvement and dystrophin production.
The placebo-controlled multiple ascending dose study enrolled ambulatory participants aged four to 20 years with confirmed exon 44 skipping amenable DMD mutations. In Cohort 1, eight participants aged six to 17 years were randomized 3:1 to receive three intravenous doses of ENTR-601-44 at 6 mg/kg or placebo.
Treated participants showed a 2.36% increase in dystrophin over a 4.0% baseline and a 2.31% increase in exon skipping over a 2.66% baseline. The study also demonstrated statistically significant improvement in Time to Rise (TTR) velocity versus placebo in a post hoc analysis (p<0.05). Entrada reported a mean TTR velocity change versus placebo of 0.115, approximately 3.5 times above the minimal clinically important difference threshold of 0.023.
Safety findings showed all treatment-emergent adverse events were mild to moderate, with no serious adverse events, deaths, or discontinuations reported. Headache was the most common adverse event. Kidney function markers, including eGFR, cystatin C, and magnesium, remained within normal ranges and comparable to placebo. All participants have transitioned into the open-label Phase 2 portion of the study.
Entrada also observed lower plasma exposure in pediatric participants compared with healthy adult volunteers and adult nonhuman primates. The company said the findings were consistent with recently generated juvenile nonhuman primate data and informed updated pharmacokinetic modeling for Cohort 2, which is evaluating a higher 12 mg/kg dose.
Chief Executive Officer Dipal Doshi said the results demonstrated favorable safety and clinically meaningful early functional benefit, while updated pharmacokinetic insights strengthened confidence in Cohort 2. President of R&D Natarajan Sethuraman, PhD, highlighted the company’s delivery platform and its potential role in muscle repair through satellite cell access.
Dr. Laurent Servais, Professor of Paediatric Neuromuscular Diseases at the University of Oxford and principal investigator of the study, said the Cohort 1 findings were encouraging and underscored the need for targeted Duchenne therapies capable of improving both short- and long-term functional outcomes. He added that he looks forward to upcoming Cohort 2 data.
ENTR-601-44 is an investigational exon 44 skipping therapy designed for people with Duchenne muscular dystrophy caused by mutations amenable to exon 44 skipping, representing about 8% of the global Duchenne population. The therapy aims to restore functional dystrophin production by targeting the underlying genetic defect.
Entrada expects to report data from the Cohort 1 open-label extension and Cohort 2 by year-end 2026.
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About the Writer
Farha Farheen, Pharm.D (LinkedIn), is a pharmacy professional with a strong interest in pharmacovigilance and clinical research. She has completed her Doctor of Pharmacy (Pharm.D) along with her internship as a Clinical Pharmacist. She has hands-on experience in adverse drug reaction (ADR) reporting, safety data documentation, and pharmacovigilance workflows, and is proficient in using VigiFlow. She is also a patent holder for an antibacterial formulation enriched with bioactive substances, granted by the German Patent and Trademark Office.