FDA Rejects Capricor's DMD Cell Therapy, Raising Questions About Regulatory Shifts
The U.S. Food and Drug Administration (FDA) has rejected Capricor Therapeutics' application for deramiocel, a cell therapy aimed at treating cardiomyopathy associated with Duchenne muscular dystrophy (DMD). This decision, which came earlier than expected, has sent shockwaves through the pharmaceutical industry and raised questions about potential shifts in regulatory approaches under new FDA leadership.
Rejection Details and Company Response
In a complete response letter (CRL) issued to Capricor, the FDA cited insufficient evidence to establish deramiocel's effectiveness, stating that the application fell short of the "statutory requirement for substantial evidence of effectiveness." The agency has requested additional clinical data to support the therapy's efficacy.
Capricor CEO Linda Marbán expressed surprise at the decision, stating, "We have followed their guidance throughout the process." The company's shares plummeted by 40% in pre-market trading following the announcement, dropping from $11.40 to $6.79 per share.
The FDA's decision came seven weeks ahead of the scheduled August 30 PDUFA date, catching many industry observers off guard. Capricor plans to resubmit its application, bolstered by upcoming results from the Phase III HOPE-3 trial, expected in the third quarter of this year.
Regulatory Landscape and Industry Implications
The rejection of deramiocel comes amid significant changes in FDA leadership, particularly within the cell and gene therapy division. Recent months have seen the departure of key officials, including Nicole Verdun, the former top regulator of cell and gene therapies at the FDA's Center for Biologics Evaluation and Research (CBER).
These personnel changes have coincided with what appears to be a shift in regulatory approach. The cancellation of a previously scheduled advisory committee meeting for deramiocel by CBER Director Vinay Prasad has fueled speculation about evolving standards for cell and gene therapies.
The FDA's decision on deramiocel follows other recent setbacks in the DMD space. Last month, the agency rejected Edgewise Therapeutics' skeletal myosin blocker sevasemten, citing insufficient data. Additionally, Sarepta Therapeutics reported a second patient death linked to its approved DMD therapy Elevidys, raising concerns about the safety of adeno-associated virus-based gene therapies.
Technical Details and Clinical Data
Deramiocel is composed of allogeneic cardiosphere-derived cells (CDC), a rare subset of heart cells shown to reduce fibrosis and modulate immune response. Capricor's application was supported by data from the Phase II HOPE-2 study, which demonstrated significant improvements in upper-limb strength and performance in treated patients.
Open-label extension data published in June 2024 suggested that deramiocel could maintain these upper-limb benefits beyond three years of treatment and stabilize left ventricular ejection fraction, indicating potential preservation of heart function in DMD patients.
The ongoing Phase III HOPE-3 trial, involving approximately 100 patients, is expected to provide additional data that Capricor believes could address the FDA's concerns. This placebo-controlled study may prove crucial in determining the future of deramiocel and potentially reshaping the regulatory landscape for cell therapies in rare diseases.
References
- Capricor Plunges on FDA Rejection of DMD Cell Therapy
In its complete response letter, the FDA cited insufficient evidence establish deramiocel's effectiveness for cardiomyopathy associated with Duchenne muscular dystrophy. The decision comes after CBER Director Vinay Prasad canceled an advisory committee meeting for the therapy.
- FDA turns back Capricor’s Duchenne cell therapy
The company said it was “surprised” by the decision, which followed the ouster of cell and gene therapy officials from the agency during deramiocel’s review.
- FDA rejects Capricor’s DMD cell therapy, asks for more data
The FDA has rejected Capricor Therapeutics’ filing for approval of a Duchenne muscular dystrophy cell therapy, raising questions about whether the agency's new leadership may be rowing back from some of the flexibility shown by the old regime. Capricor’s share price fell 38% to $7.11 in premarket trading.
Explore Further
What additional clinical data does the FDA require for deramiocel to demonstrate substantial evidence of effectiveness?
How might the recent FDA leadership changes impact the regulatory standards for cell and gene therapies?
What are the potential implications of Capricor's upcoming Phase III HOPE-3 trial results on its future application for deramiocel?
What safety concerns have been raised surrounding adeno-associated virus-based gene therapies, and how do they relate to the current industry challenges?
Who are the main competitors of Capricor in the cell therapy market for treating Duchenne muscular dystrophy, and what clinical evidence supports their therapies?