FDA removes clinical hold on Entrada’s Duchenne therapy

Entrada Therapeutics can plough on with the development of its Duchenne muscular dystrophy (DMD) therapy, ENTR-601-44, now that the US Food and Drug Administration (FDA) has lifted a two-year clinical hold.

The company can now initiate a Phase Ib study evaluating the investigational exon 44 skipping therapy in adults with a confirmed DMD gene mutation, in the US. Adult DMD patients are often excluded from clinical trials due to disease progression, said Entrada’s CEO Dipal Doshi. Entrada estimates that nearly half of those with DMD who are eligible for exon 44 skipping therapy are adults.

The FDA placed a clinical hold on ENTR-601-44 in December 2022, requesting additional information from Entrada. Although the company submitted the requested data in 2023, the agency declined to lift the hold in November of that year.

The UK Medicines and Healthcare products Regulatory Agency (MHRA) was more lenient, accepting Entrada’s data and authorising a Phase I study in August 2023. This trial, conducted in 33 healthy volunteers, evaluated safety, tolerability, and pharmacokinetics. The results showed no serious adverse events and demonstrated significant plasma and muscle concentrations of the drug, along with exon skipping activity.

Following these results, the MHRA approved the Phase I/II ELEVATE-44-102 study in the UK this month. This study will evaluate ENTR-601-44 in both healthy volunteers and patients with DMD, with enrolment expected to begin in Q2 2025.

The Phase Ib trial in the US will enrol approximately 32 ambulatory and non-ambulatory adults with specific mutations amenable to exon 44 skipping. Entrada plans to begin enrolling patients in H1 2026, with patients dosed every six weeks across four cohorts. Entrada said that participants may also be eligible to enter an open-label extension study for further assessment of safety, efficacy, and tolerability over an extended period.

Duchenne muscular dystrophy is a rare, progressive genetic disorder caused by mutations in the DMD gene, which encodes for the dystrophin protein. The absence of functional dystrophin leads to muscle weakness, loss of mobility, and life-threatening heart and respiratory complications. DMD usually affects boys in early childhood, and people with the condition may only live into their 20s or 30s.

The market for DMD therapies is expected to grow significantly over the next decade. According to GlobalData’s Pharma Intelligence Center, sales across the seven major markets (US, France, Germany, Italy, Spain, the UK, and Japan) are projected to rise from $2.3bn in 2023 to $5.2bn by 2033.

This expansion is primarily driven by the recent approvals of innovative therapies, notably Roche/Sarepta Therapeutics’ Elevidys (delandistrogene moxeparvovec) and Santhera Pharmaceuticals’ Agamree (vamorolone), said Asiyah Nawab, a healthcare analyst at GlobalData.

GlobalData is the parent company of Pharmaceutical Technology.

Source:
https://www.pharmaceutical-technology.com/news/fda-removes-clinical-hold-on-entradas-duchenne-therapy/?cf-view

PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.

Related News

Related Services