AOC 1044 receives FDA orphan drug designation for DMD

The exon 44-skipping therapy was also granted fast track designation

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to AOC 1044, an experimental exon 44-skipping therapy for Duchenne muscular dystrophy (DMD) that’s being developed by Avidity Biosciences.

Orphan drug designation is given to therapies with the potential to treat rare disorders, those that affect fewer than 200,000 people in the U.S. The designation confers certain incentives including a guarantee of seven years of market exclusivity if AOC 1044 is ultimately approved.

The new designation comes just a few months after AOC 1044 won FDA fast track designation, which is designed to speed up the development of therapies with the potential to substantially improve care for serious or life-threatening conditions.

“We are pleased that the FDA has granted both Orphan Drug and Fast Track designation to AOC 1044, highlighting the importance of advancing new treatments for people living with DMD,” Steve Hughes, MD, chief medical officer at Avidity, said in a company press release.

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DMD is caused by mutations in the DMD gene that provides instructions for making the protein dystrophin. This protein normally helps protect muscle cells from wear-and-tear damage; in DMD the dystrophin protein is lacking, which leads to symptoms of progressive muscle damage and weakness.

Within a cell’s DNA, the DMD gene is composed of multiple sections called exons, which are interspersed with other DNA called introns that don’t provide instructions for making protein. When the gene is read to make dystrophin protein, the genetic code is copied into a temporary molecule called pre-messenger RNA, and then each of the exons is spliced together to form the final protein-coding sequence.

Many DMD-causing mutations disrupt the exons’ ability to fit together properly, which prevents any dystrophin protein from getting made. Exon-skipping is a strategy that aims to leave out some exons from the mutated gene when a protein is produced, allowing the rest of the exons to fit together correctly. The ultimate goal is to allow cells to make a shortened, but still functional, version of the dystrophin protein.

AOC 1044 is specifically designed to treat DMD in patients with mutations that are amenable to skipping of exon 44. Although several exon-skipping therapies are currently available in the U.S., none are specifically designed to skip exon 44.

“There are currently no treatment options that target the underlying cause of DMD44. AOC 1044 is designed to specifically skip exon 44 of the dystrophin gene to enable the production of functional dystrophin protein,” Hughes said.

EXPLORE44 clinical trial testing AOC 1044

Avidity is sponsoring a clinical trial called EXPLORE44 (NCT05670730) to test AOC 1044 against a placebo in healthy volunteers and DMD patients with mutations amenable to exon 44 skipping.

The study is open to healthy adults ages 18 to 55, and DMD patients with eligible mutations ages 7 to 27. Enrollment is ongoing at a study site in Texas.

“We look forward to advancing AOC 1044 in clinical development and bringing this very important treatment to patients as quickly and safely as possible,” Hughes said.