Preliminary drug trial results give hope to those with a common form of muscular dystrophy

An experimental drug designed to treat one of the most common forms of muscular dystrophy successfully reduced levels of a rogue protein that causes the disease, according to preliminary results of a multi-site clinical trial that includes the University of Kansas Medical Center.

The early results in the Phase 1/2 FORTITUDE trial showed that the drug, dubbed del-brax by manufacturer Avidity Biosciences, decreased the expression of a gene called DUX4 that is usually unexpressed (inactive) in healthy people but makes toxic proteins in the muscle cells of people with facioscapulohumeral muscular dystrophy (FSHD). After four months, del-brax, which is short for delpacibart braxlosiran, reduced levels of DUX4 in the trial participants by an average of more than 50% and levels of DUX4-related proteins by 25%.

“The thing that is special about this trial is that it’s really our first proof of principle about this whole approach,” said Jeffrey Statland, M.D., professor of neurology at KU Medical Center and an investigator on the FORTITUDE trial. “It’s the first molecularly designed, gene-targeted trial that has been specifically designed to go in the muscle and hit this this DUX4 protein and knock it down.”

FSHD, which affects roughly 1 in 20,000 people, weakens and shrinks muscles in the face, shoulders, upper arms and lower legs. It also can also impair other muscles in the body. Currently there are no medications approved by the U.S. Food and Drug Administration for the disease, and FSHD is managed through different therapies. Twenty years ago, there were few drug trials for FSHD. But in 2010, an international group of researchers discovered the genetic basis for the disease, and in doing so identified a molecular target for treatment.

The drug also reduced levels of creatine kinase, which is an indicator of muscle damage. And participants in the trial who received del-brax saw some improvements in muscle strength and function compared with those who received the placebo. They also saw improvements compared with people in the ReSolve natural history study, which follows the progression of the disease over time in the absence of treatment.

Statland cautioned that these results are preliminary, after just four months, and come from a small number of participants. Participants in the study receive treatment or a placebo for nine months, after which there is a three-month follow-up period.

Over the last decade, Statland has focused on preparing the research community for clinical trials for FSHD. He and his mentor, then at the University of Rochester Medical Center, established the FSHD Clinical Trial Research Network. There are now 21 academic medical centers in 10 countries in this network, and KU is the coordinating center.  

“We're really excited about these gene-targeted therapies, and there’s also a trial going on right now for muscle regenerative therapy and a repurposed drug that's in a Phase 3 study,” said Statland. “So for FSHD, we have studies that are in Phases 1-3, all going on at the same time with multiple approaches to therapy. That's what you want to see for drug development for a rare disease.”