Avidity’s FSHD Drug Gains FDA Support for Accelerated Approval Path

Highlights

• The FDA has invited Avidity Biosciences to submit an accelerated approval application for delpacibart braxlosiran in FSHD.
• Delpacibart braxlosiran improved mobility and muscle strength in a Phase I/II trial (FORTITUDE), with no severe side effects.
• Avidity will begin a global Phase III trial (FORWARD) and aims to file a BLA in the second half of 2026.
• The drug targets DUX4 mRNA using an antibody-siRNA delivery mechanism—potentially the first disease-modifying therapy for FSHD.
• The company’s broader pipeline includes therapies for Duchenne and myotonic dystrophies and a major cardiovascular collaboration with Bristol Myers Squibb.

FDA Opens Door for Accelerated Application

Avidity Biosciences has received a green light from the U.S. Food and Drug Administration (FDA) to pursue accelerated approval for its investigational therapy, delpacibart braxlosiran. The San Diego–based biotech company announced on Monday that it aims to submit a biologics license application (BLA) for the drug in the second half of 2026. If approved, the therapy would mark the first disease-modifying treatment for facioscapulohumeral muscular dystrophy (FSHD), a rare genetic muscle disorder.

Avidity’s drug candidate, an antibody-oligonucleotide conjugate, demonstrated significant improvements in mobility and muscle strength in early-stage clinical trials. "Today’s updates are significantly positive for [Avidity]," wrote BMO Capital Markets analysts, emphasizing that the "FDA’s 'endorsement of [delpacibart braxlosiran] AA pathway is a big win."

Positive Clinical Trial Results from FORTITUDE Study

The company shared topline results from its Phase I/II FORTITUDE trial involving patients with FSHD. This form of muscular dystrophy initially weakens muscles in the face and upper body and can eventually affect the entire body. Patients receiving delpacibart braxlosiran showed notable progress in mobility and muscle strength, outperforming the placebo group across assessments such as the 10-meter walk-run test, timed up and go test, and quantitative muscle testing.

Additionally, biomarker analysis revealed a reduction in KHDC1L and creatine kinase levels—both indicators of muscle damage. The trial reported no serious or severe adverse effects, and no participants discontinued due to side effects.

Path Forward: Phase III Trial and Research Presentation

To bolster its regulatory submission, Avidity plans to initiate a global Phase III study titled FORWARD. This confirmatory trial will run alongside an existing registrational study aimed at collecting further biomarker data.

The company will also share more comprehensive findings at the 32nd Annual FSHD Society International Research Congress, scheduled for June 12–13 in Amsterdam.

Mechanism of Action: Targeting the Root Cause

FSHD is triggered by the abnormal expression of a protein known as DUX4. Delpacibart braxlosiran employs a targeted delivery approach using an antibody to engage the transferrin receptor, delivering an siRNA molecule that degrades DUX4 mRNA. This makes delpacibart braxlosiran the first therapeutic designed to address the underlying genetic cause of FSHD, according to Avidity.

Broader Pipeline and Industry Impact

Despite the promising news, Avidity's shares fell over 11% to $32.14 as of 11:17 a.m. ET on Monday. Nevertheless, the company remains a key player in the muscular dystrophy field. Its pipeline includes delpacibart zotadirsen, an exon-skipping therapy for Duchenne muscular dystrophy, which showed a 25% increase in dystrophin production in a Phase I/II trial in August 2024—described by the company as “unprecedented.”

Furthermore, the FDA granted breakthrough therapy designation to Avidity’s treatment for myotonic dystrophy type I in 2024. The company's platform continues to attract substantial investment, including a deal with Bristol Myers Squibb in 2023 worth up to $2.3 billion to explore applications of Avidity’s antibody-oligonucleotide technology in five cardiovascular indications.