Avidity Biosciences' Del-Brax: A Breakthrough in FSHD and the Power of Accelerated Approval

The biotech sector is littered with stories of drugs that show promise in early trials but falter in late-stage studies. But what if a company could bypass some of that risk by leveraging the FDA's accelerated approval pathway? Avidity Biosciences (AVDX) is now at that pivotal juncture with its lead candidate del-Brax, a potential first-in-class treatment for facioscapulohumeral muscular dystrophy (FSHD). With the FDA's accelerated approval pathway now open and a robust clinical trial design, del-Brax could soon become a landmark therapy for a devastating disease that currently has no approved treatments. Here's why investors should pay attention.

The Unmet Need: FSHD's Devastating Toll

FSHD affects approximately 45,000 to 87,000 people in the U.S. and Europe, causing progressive muscle weakness and functional decline. Unlike more well-known muscular dystrophies, FSHD has no approved therapies, leaving patients with no option but to manage symptoms. The disease is driven by the overexpression of the DUX4 protein, which del-Brax targets directly using a novel mechanism: a monoclonal antibody-siRNA conjugate that binds to the transferrin receptor 1 (TfR1) to deliver siRNA into muscle cells, silencing DUX4 mRNA.

Accelerated Approval: The Biomarker Play

The FDA's accelerated approval pathway is a double-edged sword. It allows drugs to be approved based on a surrogate endpoint that is reasonably likely to predict clinical benefit—but requires confirmatory trials post-approval. For del-Brax, the surrogate is KHDC1L, a DUX4-regulated circulating biomarker. Early data from the Phase 1/2 FORTITUDE trial showed reductions of over 50% in DUX4-regulated genes and trends toward functional improvements in muscle strength and mobility.

The key now is validation. Avidity must show that lowering KHDC1L directly correlates with slowing disease progression or improving function. If successful, this biomarker-driven approach could fast-track del-Brax's approval by late 2026, with topline FORTITUDE data expected in Q2 2026. This timeline is critical: the FDA has already signaled openness to the pathway, and the company is preparing a Biologics License Application (BLA) accordingly.

Clinical Momentum: Phase 3 and Beyond

While the FORTITUDE trial focuses on biomarkers, the Phase 3 FORWARD trial is designed to deliver the “real-world” data needed for full FDA approval. Enrolling ~200 patients globally, FORWARD uses functional endpoints like quantitative muscle testing (QMT) and mobility assessments (e.g., the 10-Meter Walk-Run Test). Importantly, the trial is flexible—should biomarker data hold, Avidity can elevate functional measures to primary endpoints, streamlining the path to approval.

The trial's global reach (sites in North America, Europe, and Japan) and open-label extension (FORTITUDE-OLE) for long-term safety/efficacy data also suggest Avidity is thinking strategically about market access and durability. With no competing therapies in late-stage development, del-Brax's first-mover advantage could be substantial.

Risks and Realities

Of course, no drug is without risks. The biggest question mark is whether the FORTITUDE biomarker data will confirm early trends. If KHDC1L reduction doesn't translate to functional benefits, the FDA could demand more data, delaying approval. Additionally, rare-disease trial logistics—like patient recruitment and retention—are ever-present hurdles.

Another wild card: competition. While no direct competitors are in late-stage trials, Avidity's pipeline includes other programs (e.g., del-desiran for myotonic dystrophy), which could distract resources. Still, FSHD's unmet need and del-Brax's mechanism-specific targeting give it a strong edge.

Investment Takeaways

For investors, Avidity's stock (AVDX) represents a high-risk, high-reward play. The FDA's green light on the accelerated pathway has already buoyed sentiment, but the next catalysts are clear:
- Q2 2026: FORTITUDE biomarker data. A miss here could crater the stock.
- H2 2026: BLA submission and potential accelerated approval.

If del-Brax gains accelerated approval, the upside is significant. The FSHD market, though small, is concentrated and desperate for options. Plus, del-Brax's mechanism could open doors to other diseases involving DUX4 or TfR1 pathways.

Final Verdict

Avidity is executing flawlessly on a strategy that combines regulatory agility with a scientifically sound approach. The FDA's accelerated pathway isn't just a shortcut—it's a recognition of del-Brax's potential to transform lives. Investors should monitor FORTITUDE data closely. If the biomarker data holds, AVDX could be a multi-bagger. But remember: this is still a high-stakes race. Proceed with caution, but don't ignore the finish line.

Consider Avidity as a speculative buy for investors with a high risk tolerance, with a target price tied to positive FORTITUDE readouts.