FDA Activity Recap: July 2025 Features Multiple CRLs, RMAT Designation, and More

Last month, July 2025, the CGTLive^® team was diligently tracking the FDA's activities related to the development of cell and gene therapies for the treatment of rare, complex, and otherwise challenging diseases and disorders.

The agency has continued to ramp up its activities around these therapies as more of them progress through the pipeline in tandem. Last month proved no different, with the FDA issuing complete response letters (CRLs) to Ultragenyx and Capricor Therapeutics and granting regenerative medicine advanced therapy (RMAT) designation to Rocket Pharmaceuticals’ RP-A601. Our team has highlighted these, and several other important actions, below.

Click the read more buttons for more details and information about each update.

FDA Gives Sarepta Green Light to Restart Shipment of DMD Gene Therapy Elevidys to Patients who are Ambulatory

July 30, 2025 — The FDA has recommended that Sarepta Therapeutics remove its voluntary hold on United States shipments of Duchenne muscular dystrophy (DMD) gene therapy delandistrogene moxeparvovec-rokl (marketed as Elevidys) for patients who are ambulatory.

In a press release announcing the recommendation, the FDA also stated that it has concluded its investigation of the death an 8-year-old boy who was treated with Elevidys in Brazil and died on June 7, 2025. The agency stated that it has deemed the boy’s death was not related to the Elevidys product.

Although the hold on shipments for Elevidys was voluntary, the FDA had informally requested that Sarepta suspend all shipments of the gene therapy product earlier in July. Initially, the company made a public statement that it would not be complying with the request, acknowledging that it had previously paused shipments to patients who are nonambulant, but would continue to ship the product to patients who are ambulant. The company justified its decision on the basis of a “comprehensive scientific interpretation of the data” that did not indicate any new or changed safety signals for Elevidys in ambulant patients.

Rocket’s PKP2-Arrhythmogenic Cardiomyopathy Gene Therapy RP-A601 Snags RMAT Designation

July 29, 2025 — Rocket Pharmaceuticals’ RP-A601, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat plakophilin-2 related arrhythmogenic cardiomyopathy (PKP2-ACM), has received RMAT designation from the FDA.

According to Rocket, the RMAT designation was granted based on results from a phase 1 clinical trial (NCT05885412) evaluating RP-A601. Notably, the gene therapy has previously received fast track designation and orphan drug designation (ODD) from the FDA and ODD from the European Commission.

“The FDA’s RMAT designation for RP-A601 represents a meaningful advancement for Rocket and for patients living with PKP2-ACM, a life-threatening genetic heart disease characterized by ventricular arrhythmias and sudden cardiac death,” Kinnari Patel, PharmD, MBA, the president and head of R&D at Rocket Pharmaceuticals, said in a statement. “This marks the fifth RMAT designation in our history and underscores our commitment to developing potentially curative gene therapies for patients with rare and inherited cardiovascular diseases. The early clinical data for RP-A601 are highly encouraging, and we look forward to continued collaboration with the FDA throughout the program’s development.”

FDA Revokes Sarepta’s Platform Technology Designation for Muscular Dystrophy Gene Therapy Vector Following Patient Deaths

July 22, 2025 — Sarepta Therapeutics’ platform technology designation from the FDA for the AAVrh74 viral vector it uses in gene therapy products for multiple muscular dystrophy indications has been revoked by the agency.

The FDA’s decision follows the recent death of a 51-year-old patient who was treated with Sarepta’s investigational gene therapy SRP-9004 for nonambulant limb-girdle muscular dystrophy (LGMD) type 2D/R3, which uses the AAVrh74 serotype, in a phase 1 clinical trial (DISCOVERY; NCT01976091). In its announcement of the revocation, the FDA also made reference to 2 previous deaths that occurred among inpatients who received delandistrogene moxeparvovec-rokl (Elevidys), the company’s marketed AAV vector–based gene therapy for DMD, which also uses the AAVrh74 vector. The agency noted that all 3 deaths seem to have been caused by acute liver failure (ALF).

In addition to revoking the platform technology designation, the FDA also placed clinical holds on all trials currently evaluating SRP-9004 and bidridistrogene xeboparvovec (also known as SRP-9003), which is an investigational gene therapy product in development by Sarepta for LGMD type 2E (also known as β-sarcoglycanopathy), which also uses the AAVrh74 vector. On July 18, the FDA also informally requested that Sarepta pause all shipments of Elevidys in the United States, a request that Sarepta initially stated it would not fulfill until reversing its position on the matter several days later.

Ultragenyx’s MPS IIIA Gene Therapy UX111 Met With CRL

July 14, 2025 — Ultragenyx has received a CRL from the FDA regarding its biologics license application (BLA) for UX111 (ABO-102), an AAV vector-based gene therapy intended to treat mucopolysaccharidosis type IIIA (MPS IIIA, also known as Sanfilippo syndrome).

According to Ultragenyx, the CRL relates to a need for additional chemistry, manufacturing and controls (CMC) information and improvements and observations from inspections of manufacturing facilities that were conducted recently. The company noted its perception that the concerns are related to facilities and processes rather than to the quality of the gene therapy product itself, and that the observations are “readily addressable”. Furthermore, Ultragenyx stated that it plans to work with the agency to address these observations and that it plans to resubmit the BLA thereafter. Once resubmitted, a review period of up to 6 months will take place.

Ultragenyx additionally noted that the FDA indicated that the neurodevelopmental outcome data it received in the original BLA are robust and that no concerns regarding the clinical data or clinical inspections were present in the CRL. The agency also indicated that additional supportive evidence is provided by the biomarker data included in the BLA. Although, the FDA requested that updated clinical data be included in the BLA resubmission.

Capricor’s BLA for DMD Cardiomyopathy Cell Therapy Deramiocel Slammed With CRL

July 11, 2025 — Capricor Therapeutics has received a CRL from the FDA regarding its BLA for Deramiocel (also known as CAP-1002), an investigational allogeneic cardiosphere-derived cell therapy that was under review for the treatment of DMD cardiomyopathy.

In the CRL, the FDA stated that the statutory requirement for “substantial evidence of effectiveness” was not met by the BLA and that more clinical data will be needed. Furthermore, the FDA also drew attention to outstanding parts of the BLA’s CMC section, that were not reviewed by the agency because of the CRL’s timing. Although Capricor stated that most of these CMC items have been addressed previously in its interactions with the agency.

Capricor has stated its intent to resubmit the BLA in the third quarter of this year, with additional data from the phase 3 HOPE-3 clinical trial (NCT05126758). The initial BLA did not include data from this ongoing study, but was instead supported only by data from the completed HOPE-2 clinical trial (NCT03406780) and HOPE-2’s ongoing open-label extension (OLE) study (HOPE-2-OLE; NCT04428476), with data from these studies being compared to an FDA funded natural history dataset. The FDA stated that the review clock will be restarted when the BLA is resubmitted and that the Capricor may request a Type A meeting focused on the way to move forward.