DYNE-251 for DMD, DYNE-101 for DM1 showing safety in early trials

Phase 1/2 studies, both enrolling patients, include open-label extensions

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

The words

DYNE-251, an experimental treatment for Duchenne muscular dystrophy (DMD), is being well tolerated by patients in an ongoing clinical trial, according to the therapy’s developer, Dyne Therapeutics.

Dyne also reported positive safety data from an ongoing trial of DYNE-101, the company’s investigational therapy for myotonic dystrophy type 1 (DM1).

“To date, the safety profile in the clinic has been favorable for DYNE-101 and DYNE-251 and has supported dose escalation to a combined nine cohorts across both trials,” Joshua Brumm, president and CEO of Dyne, said in a company press release.

Initial findings into each treatment’s potential effectiveness are expected early next year, Brumm added.

Recommended Reading
An illustration shows multiple hands giving a thumbs up sign within a black circle.

FDA approves vamorolone, now Agamree, for DMD patients 2 and older

Muscular dystrophy clinical trials enrolling patients at sites worldwide

DMD is caused by mutations in the gene that encodes dystrophin, a protein that helps cushion muscle cells against damage. DYNE-251 is an exon-skipping treatment designed to mask a section of this gene called exon 51, which may facilitate the production of functional dystrophin protein in about 13% of DMD patients.

Dyne is running a Phase 1/2 clinical trial called DELIVER (NCT05524883), testing DYNE-251 in boys with DMD ages 4 to 16 who have mutations amenable to exon 51 skipping. The trial has completed enrollment of five cohorts. In each of these groups, a few patients are being given placebo, while the others are being treated with DYNE-251 at doses ranging from 0.7 mg/kg to 10 mg/kg, given by infusion into the bloodstream every four weeks.

So far more than 175 doses of DYNE-251 have been given in DELIVER, and safety data have been positive — no one has experienced anemia or quit the study. The trial is now recruiting eligible patients at sites across North America, Europe and Australia for a sixth cohort, which will test a higher dose of 20 mg/kg.

Data from this sixth cohort will determine whether a seventh patient group will test a dose of 40 mg/kg.

Another Phase 1/2 clinical trial, ACHIEVE (NCT05481879), is testing DYNE-101 in adults with DM1 ages 18 to 49 at sites across Europe and in New Zealand. This experimental therapy is designed to reduce the production of toxic messenger RNA from the DMPK gene that causes DM1.

ACHIEVE has completed enrollment in two patient groups, testing doses of 1.8 mg/kg given every four weeks, and 3.4 mg/kg given every four weeks or eight weeks.

Safety data from ACHIEVE also have been positive, without any cases of anemia or discontinuations. Participants are now being enrolled in a third cohort testing a 6.8 mg/kg dose. A fourth cohort to test doses up to 10.2 mg/kg is contingent on results from this third group.

Early biomarker and other efficacy data due to be released in January

Both DELIVER and ACHIEVE include an initial placebo-controlled trial portion running about six months, after which patients can enter into open-label extensions where everyone is treated for 24 weeks. So far, all who have completed the placebo-controlled trial phase opted to move into the open-label extension.

Continuing with treatment in a long-term extension study, running for almost two years (96 weeks), then will be offered to patients.

“We’ve made tremendous progress in our ACHIEVE and DELIVER trials with more than 72 patients enrolled and over 300 doses administered thus far,” Brumm said.

“We are moving with great excitement towards reporting initial data … including the important biomarker of splicing and functional outcome of myotonia in DM1 and dystrophin in DMD,” he added. “We look forward to sharing both readouts around the time of the J.P. Morgan Healthcare Conference in early January 2024.”