FDA Lifts Clinical Hold on Entrada's DMD Drug, Paving Way for Phase 1b Study

Entrada Therapeutics has received clearance from the U.S. Food and Drug Administration (FDA) to proceed with its phase 1b study of ENTR-601-44, a potential treatment for Duchenne muscular dystrophy (DMD). This decision marks the end of a more than two-year-long clinical hold, signaling a significant milestone for the company and potential hope for DMD patients.

Entrada's ENTR-601-44: A Long-Awaited Green Light

ENTR-601-44, an endosomal escape vehicle-conjugated phosphorodiamidate morpholino oligomer, targets DMD patients with mutations amenable to exon 44 skipping. The FDA initially placed the drug on hold in December 2022, requesting additional information from Entrada. Despite submitting a supplementary data package in November 2023, the company faced continued regulatory hurdles.

Now, with the FDA's approval, Entrada can launch the ELEVATE-44-102 study, expected to commence in the first half of 2026. This phase 1b trial will evaluate ENTR-601-44 in adult DMD patients, including both ambulatory and non-ambulatory individuals.

Entrada CEO Dipal Doshi expressed optimism about the development, stating, "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."

Advancing DMD Treatment Landscape

While ENTR-601-44 faced regulatory challenges in the U.S., other companies made significant strides in DMD treatment:

1. Sarepta Therapeutics secured FDA approval for its DMD gene therapy, Elevidys, in 2023.
2. RegenXBio is progressing its gene therapy candidate into late-stage testing.
3. PTC Therapeutics and Santhera have FDA-approved daily corticosteroids for DMD patients aged 2 and older.
4. Italfarmaco's Duzyvat became the first FDA-approved nonsteroidal drug for DMD patients 6 and older in 2023.
5. Cumberland Pharmaceuticals recently reported positive phase 2 results for its active thromboxane receptor antagonist in DMD.

These developments underscore the dynamic nature of DMD research and the potential for multiple treatment options to address this devastating genetic disorder.

Looking Ahead: ELEVATE-44-102 and Beyond

As Entrada prepares to initiate the ELEVATE-44-102 study in the U.S., the company is simultaneously moving forward with a phase 1 trial of ENTR-601-44 in the United Kingdom. This dual-pronged approach may accelerate the drug's development timeline and provide valuable data from diverse patient populations.

The inclusion of both ambulatory and non-ambulatory adult patients in the ELEVATE-44-102 study addresses a critical gap in DMD clinical research. As Doshi noted, these patients are "unfortunately often left out of clinical studies due to the advanced stage of their disease."

With the FDA hold lifted and multiple companies advancing DMD treatments, the pharmaceutical industry continues to make strides in addressing the unmet needs of patients living with this challenging condition.