How a Setback Could Shape the Next Era of Gene Therapy

FDA reverses a key vector designation, pushing developers toward tighter data and safer strategies

19 Jul 2025

US regulators are signalling a more demanding framework for future gene therapy development after patient deaths in trials using the rAAVrh74 vector, a shift expected to influence how companies plan studies, assess risk and design new delivery systems.

The inflection point came after the US Food and Drug Administration withdrew federal recognition previously granted to Sarepta Therapeutics for its rAAVrh74 platform. The earlier designation had suggested potential efficiencies across multiple programmes, though the agency emphasised that each product would still require independent review for safety, manufacturing quality and clinical design.

The withdrawal, following fatalities in studies using the same vector, including one in Sarepta’s SRP-9004 trial, has prompted developers to strengthen safety packages and revisit assumptions about platform-wide evidence. Regulators said that future platform decisions would depend on "highly consistent and clearly demonstrated evidence", reinforcing expectations for more rigorous data.

"This serves as a wake-up call," one industry observer said, noting that transparency and detailed clinical information would remain central to future assessments.

Analysts say the implications are likely to unfold over several years. While the FDA has not outlined direct consequences for other companies using similar vectors, developers are expected to incorporate earlier dialogue with regulators, tighter dose-selection strategies and more structured monitoring plans. Some foresee wider adoption of emerging vector engineering methods aimed at reducing immune responses and improving predictability, although such outcomes remain uncertain.

The episode is also shaping investment priorities. Firms are exploring manufacturing technologies that provide greater control over vector quality, as well as collaborative models that allow shared learning across programmes. These efforts aim to position new candidates more securely within an evolving regulatory environment.

Despite the setback, the sector continues to advance programmes targeting rare and common diseases. Developers are adjusting trial designs and expanding preclinical work to align with what many view as a clearer regulatory trajectory.

Industry analysts expect that higher standards will influence the next generation of gene therapies, shaping how platforms are evaluated and how evidence is assembled before late-stage trials. Whether these shifts accelerate approvals or introduce longer development cycles will depend on how effectively companies adapt to the agency's forward-looking expectations.