Trial Termination After High Hopes

On 08 December 2024, Pfizer announced the discontinuation of its Phase III CIFFREO trial evaluating fordadistrogene movaparvovec, a gene therapy for Duchenne muscular dystrophy (DMD). The decision follows an interim analysis showing the therapy failed to meet its primary endpoint of improved motor function, despite successful delivery of the dystrophin gene.

The trial enrolled boys aged 4 to 7 with confirmed DMD mutations. While the therapy was well tolerated, the lack of meaningful clinical improvement led Pfizer to halt further development and redirect resources toward alternative neuromuscular programs.

What Went Wrong?

Fordadistrogene was designed to deliver a shortened version of the dystrophin gene via an AAV9 vector. Although biomarker data confirmed expression of micro-dystrophin, it did not translate into measurable gains in motor performance, as assessed by the North Star Ambulatory Assessment (NSAA).

Experts suggest that timing, variability in disease progression, and limitations in outcome measures may have contributed to the disappointing results. The setback underscores the complexity of treating DMD and the challenges of translating molecular success into functional benefit.

Industry Implications

Pfizer’s withdrawal follows similar struggles faced by other gene therapy developers in DMD, including Sarepta and Solid Biosciences. The field is now pivoting toward combination approaches, improved vector design, and earlier intervention strategies.

Despite the setback, Pfizer reaffirmed its commitment to rare disease research and plans to continue exploring RNA-based therapies and next-generation gene editing for neuromuscular disorders.