Dynacure Gets Green Light in Europe to Begin Clinical Trial of Antisense Therapy for CNM

Rare Daily Staff

Photo: Stephane van Rooijen, CEO of Dynacure

Dynacure said the European Medicines and Healthcare products Regulatory Agency has approved its clinical trial application for DYN101, an experimental antisense therapy for the treatment of a group of rare muscle disorders known as centronuclear myopathies.

Centronuclear myopathy (CNM) is an umbrella term for a group of disorders affecting skeletal muscle tissue with variable inheritance, all of which are associated with poor prognosis. The severity of the disease differs from case to case, ranging from slightly debilitating to fatal. Most often, CNM will be present at birth, however, symptoms can manifest at any stage in life. A child born with either of these conditions will most likely show signs of low muscle tone. Most of the time, these babies will also struggle with the ability to suck, swallow, and breathe on their own.

DYN101 is an investigational antisense oligonucleotide using Ionis Pharmaceuticals’ proprietary antisense technology. It is designed to modulate the expression of dynamin 2 (DNM2) for the treatment of CNM. In preclinical animal studies, prevention and reversion of the disease was observed with a clear dose-dependent improvement in whole body strength and mice survival.

The development plan for DYN101 was designed to be very broad and it is the only known program being investigated for most CNM populations. In addition to investigating DYN101 for CNM, Dynacure expects to expand its use and explore additional indications where the overexpression of DNM2 is a disease-driving factor.

Dynacure expects to initiate its first human study in the second half of 2019. The study, Unite-CNM, is a European multicenter, ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of DYN101 in approximately 18 patients greater than 16 years of age with two forms of CNM, XLCNM, or ADCNM.

While the phase 1 / 2 study will primarily focus on finding an optimal dose of the drug via safety, tolerability and target attainment after 12 weeks of treatment, multiple domains of efficacy will also be assessed in an exploratory analysis, which include muscular function, respiratory function, and muscle strength. After completing the Unite-CNM study, Dynacure expects to investigate a potential registration-directed phase 2 / 3 study (all age groups) that would include European and U.S. sites.

“This is the first regulatory approval for a clinical trial of DYN101, representing a promising advancement for patients suffering from most forms of centronuclear and myotubular myopathies,” said Stephane van Rooijen, CEO of Dynacure. “With antisense, we believe there is an opportunity to reimagine the treatment of rare muscle-related disorders where no viable therapy exists.”