Five Advanced Therapeutics to Watch in 2H 2025

In recent years, the FDA has continued to ramp up its activities around cell therapies, gene therapies, and other advanced therapeutics as more of them progress through the pipeline for the treatment of rare, complex, and otherwise challenging diseases and disorders. The second half of this year is shaping up to continue the trend, with several Prescription Drug User Fee Act (PDUFA) dates already slated for the coming months and other companies having recently submitted biologics license applications (BLAs) to the agency or planning resubmissions in the near-term future. With 2025 having recently hit its midway point, the CGTLive^® team has highlighted 5 notable therapies to keep an eye on as the remainder of the year unfolds.

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PRGN-2012

Indication: Recurrent respiratory papillomatosis

Status: PDUFA set for August 27, 2025

February 25, 2025 - The FDA has accepted the BLA that Precigen submitted for PRGN-2012, a gene therapy product intended to treat recurrent respiratory papillomatosis (RRP) with priority review. The PDUFA action date for the BLA has been set at August 27, 2025, and no advisory committee meeting is currently planned for the BLA.

PRGN-2012 is based on the company’s AdenoVerse platform and is intended to trigger an immune response targeted at cells infected by human papillomavirus (HPV) 6 or HPV 11, thus providing an alternative to the current standard of care for RRP, which typically involves repeated surgical interventions. The BLA for PRGN-2012 is supported by results from a phase 1/2 clinical trial (NCT04724980). The study, which reached its primary completion date on June 5, 2024, enrolled 38 patients in total. It remains active, but is no longer recruiting new patients.

Clemidsogene lanparvovec

Indication: Mucopolysaccharidosis type 2

Status: PDUFA set for November 9, 2025

May 15, 2025 - The FDA has accepted REGENXBIO’s BLA clemidsogene lanparvovec (also known as RGX-121), an investigational adeno-associated virus vector-based gene therapy intended to treat mucopolysaccharidosis type 2 (MPSII, also known as Hunter syndrome). The BLA was accepted for priority review and its PDUFA action date has been set as November 9, 2025.

"Acceptance of the RGX-121 BLA marks an exciting milestone on our path to bring the MPS II patient community a one-time treatment with the potential to address both the neurodevelopmental and systemic effects of Hunter syndrome," Curran M. Simpson, the president and chief executive officer of REGENXBIO, said in a statement. "Supported by positive biomarker data and long-term outcomes, RGX-121 has the potential to be a first-in-class gene therapy that could dramatically transform the MPS II treatment landscape and reduce the significant burden patients and families currently face with weekly enzyme replacement therapy."

Sonpiretigene isteparvovec

Indication: Retinitis pigmentosa

Status: Rolling BLA submitted

July 15, 2025 - Nanoscope Therapeutics has submitted a rolling BLA to the FDA for MCO-010 (sonpiretigene isteparvovec), an investigational ambient-light activatable multi-characteristic opsin (MCO) gene therapy, for the treatment of retinitis pigmentosa (RP).

“We’ve been working on the MCO platform for more than a decade,” Samarendra Mohanty, PhD, the president, chief scientific officer, and cofounder of Nanoscope, said in a statement. “We’ve seen this investigational therapy surpass our expectations in the lab and in patients in clinical trials, and we believe we’re now one step closer to potentially bringing this pioneering therapy to all RP patients.”

The company noted that the first modules of MCO-010's BLA have been submitted to the agency and that full submission is expected to be finished early next year. The gene therapy has previously been granted fast track designation by the FDA, and thus is eligible for priority review.

Deramiocel

Indication: Duchenne muscular dystrophy cardiomyopathy

Status: Received CRL, BLA resubmission planned for Q3 2025

July 11, 2025 - Capricor Therapeutics has received a complete response letter (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 Duchenne muscular dystrophy (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 Chemistry, Manufacturing, and Controls (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.

UX111

Indication: Mucopolysaccharidosis type IIIA

Status: Received CRL, BLA resubmission planned

July 14, 2025 -Ultragenyx has received a CRL from the FDA regarding its BLA for UX111 (ABO-102), an adeno-associated virus (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 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.