FDA Advisory Committee Rejects Capricor's Deramiocel in Duchenne Muscular Dystrophy Cardiomyopathy

FDA Advisory Committee Rejects Capricor's Deramiocel in Duchenne Muscular Dystrophy Cardiomyopathy

On July 29, 2026, the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) voted 9 to 3 that the available clinical evidence does not support the effectiveness of Capricor Therapeutics’ deramiocel (CAP-1002) for the treatment of cardiomyopathy in Duchenne muscular dystrophy (DMD). While the FDA is not bound by the committee's vote, the negative outcome represents a major hurdle for the cell therapy ahead of its scheduled August 22, 2026, regulatory decision deadline.

Following the vote, Capricor’s stock plummeted by over 50%, reaching a new 52-week low and triggering multiple analyst downgrades.

The Statistical Analysis Plan (SAP) Dispute

The advisory committee's rejection was heavily driven by a contentious procedural dispute between the FDA and Capricor regarding the trial's Statistical Analysis Plan (SAP)¹:

• The FDA's Position: FDA reviewers evaluated the Phase 3 HOPE-3 trial data using SAP version 1.1, which was the plan in place when the study began. Under this model, the trial's primary endpoint—the Performance of Upper Limb version 2.0 (PUL 2.0) skeletal muscle measure—showed a mean difference of only 0.66 points (p-value of 0.24), which the FDA characterized as "not a near miss."
• Capricor's Position: Capricor argued that the FDA improperly graded the trial based on SAP 1.1, which CEO Linda Marbán, Ph.D., characterized as an "unsigned, incomplete internal draft." Capricor defended the trial using SAP version 3.0 (finalized before unblinding), under which deramiocel slowed upper limb function decline by 54% versus placebo, achieving a statistically significant p-value of 0.029.

"Fragile" Cardiac Evidence

The committee's voting question was narrowly focused on cardiomyopathy rather than the trial's primary skeletal muscle endpoint. The cardiac endpoint evaluated left ventricular ejection fraction (LVEF). Under SAP 3.0, the LVEF endpoint showed a positive trend but failed to achieve statistical significance (p-value of 0.09).

Furthermore, the FDA flagged that Capricor had changed its LVEF analysis from an absolute-change model to a ranked-change approach the day before the trial was unblinded. While Capricor stated this was a necessary adjustment due to a small cardiac cohort sample size, the FDA and committee members viewed the late change as procedurally suspect and the resulting cardiac evidence as too "fragile" and sensitive to patient inclusion.

A Split with The Lancet

In a striking collision of scientific and regulatory reviews, The Lancet published the peer-reviewed results of the HOPE-3 trial on the exact same day as the advisory committee meeting. The journal's peer reviewers accepted and validated the trial's design, findings, and statistical methodology under SAP 3.0, confirming the 54% slowing of upper limb decline.

If the FDA issues a Complete Response Letter (CRL) on August 22, Capricor's most viable path forward may be to resubmit its application built around skeletal muscle function (PUL 2.0) as the primary evidence of effectiveness, rather than the cardiac endpoints that dominated the CTGTAC meeting.