FDA Activity Recap: February 2025 Features Multiple BLA Acceptances, RMAT Designations, and More

Last month, February 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 accepting biologics license application (BLA) for Ultragenyx's mucopolysaccharidosis type IIIA (MPS IIIA, also known as Sanfilippo syndrome) gene therapy and issuing regenerative medicine advanced therapy (RMAT) designation to Asklepios BioPharmaceutical (AskBio)'s Parkinson disease (PD) gene therapy. 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 Accepts BLA for Ultragenyx’s MPSIIIA Gene Therapy UX111 With Priority Review

February 19, 2025 — The FDA has accepted the BLA that Ultragenyx submitted for UX111 (ABO-102), an AAV vector-based gene therapy intended to treat mucopolysaccharidosis type IIIA (MPS IIIA, also known as Sanfilippo syndrome), with priority review. The Prescription Drug User Fee Act (PDUFA) action date for the BLA has been set at August 18, 2025, and no advisory committee meeting is currently planned for the BLA.

The company submitted the BLA to the agency in December of last year. Notably, Ultragenyx is seeking accelerated approval for the BLA based on the use of cerebral spinal fluid (CSF) heparan sulfate (HS) data from the phase 1/2/3 Transpher A clinical trial (NCT02716246), which will be used as a surrogate end point. Ultragenyx previously announced earlier in 2024 that it had participated in a meeting with the FDA in which the company and the agency came to an agreement that CSF HS may be used as a surrogate end point for this purpose. In addition to the Transpher A data, the BLA is also supported by long-term safety findings from a separate phase 1/2 clinical trial (NCT04088734). This trial, which was originally launched on September 18, 2019, has been formally terminated, but is continuing to follow up with patients annually until 5 years posttreatment to collect additional safety data.

“Acceptance of the UX111 BLA brings us closer to being able to provide a first-ever treatment for Sanfilippo syndrome type A and, if our application is successful, we’re prepared to launch this therapy for patients and their families,” Emil D. Kakkis, MD, PhD, the chief executive officer and president of Ultragenyx, said in a statement. “By reaching alignment with the agency on a path forward for accelerated approval in neuronopathic MPS diseases, our UX111 program could serve as a step towards advancing drug development across multiple metabolic diseases of the brain.”

FDA Accepts BLA for Precigen’s Recurrent Respiratory Papillomatosis Gene Therapy PRGN-2012 With Priority Review

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.

"The priority review designation is a testament to the FDA's recognition of the significant unmet need for the RRP patient population,” Helen Sabzevari, PhD, the president and chief executive officer of Precigen, said in a statement. “RRP patients have never had an FDA-approved therapy, relying instead on repeated surgeries to alleviate the symptoms of RRP without addressing the underlying disease. Treatment with PRGN-2012 has shown significant, durable clinical benefit. We have patients treated with PRGN-2012 who have been surgery-free for more than 3 years now, bringing hope for an alternative to the cycle of repeated surgeries, which carry immense risk for irreversible damage and significant morbidity. We look forward to working with the FDA over the coming months during their BLA review and hope to introduce the first FDA-approved therapeutic option to the RRP patient population, estimated at more than 27,000 adults in the United States, later this year."

Gradalis' Personalized Immunotherapy Gemogenovatucel-T Receives FDA RMAT Designation

February 5, 2025 — Gradalis' Gemogenovatucel-T (also known as Vigil), an investigational personalized cellular immunotherapy currently being evaluated for the treatment of ovarian cancer, has received RMAT designation from the FDA.

The product is being evaluated in the ongoing randomized, placebo-controlled phase 2b VITAL clinical trial (NCT02346747) in patients with newly diagnosed, advanced stage IIIb/IV ovarian cancer who are homologous recombination proficient (HRP), have a high clonal tumor mutation burden (cTMB-H), and who remain in complete response after debulking surgery and frontline platinum-based doublet chemotherapy. According to the clinicaltrials.gov page, which was most recently updated on January 9, 2025, VITAL is active, but no longer recruiting new patients. It was initiated in February 2015 and has an estimated completion date of December 2025. The total enrollment for the study is listed as 92 patients. According to Gradalis, results from the study showing a statistically significant and clinically meaningful improvement in overall survival (OS) in patients with HRP ovarian cancer and cTMB-H informed the FDA's decision to grant the RMAT designation, which applies specifically to that indication.

“The RMAT designation for Vigil highlights the transformative capacity of our unique immunotherapy to benefit women battling advanced ovarian cancer,” David Shanahan, BS, the chief executive officer of Gradalis, said in a statement. “This important recognition affirms that Vigil has the potential to extend patient survival and may offer a safer, more precise therapeutic approach to a population in urgent need of innovative solutions. We continue to advance our Vigil development efforts as we work to bring this investigational therapy to patients as rapidly as possible.”

AskBio Garners RMAT Designation for Parkinson Disease Gene Therapy AB-1005

February 24, 2025 — Bayer subsidiary AskBio's AB-1005 (AAV2-GDNF), an investigational AAV vector serotype 2 (AAV2)-based gene therapy intended to treat Parkinson disease (PD), has received RMAT designation from the FDA.

The FDA’s decision was based on a review of findings from a phase 1b clinical trial (NCT04167540), which has passed its primary completion date but is continuing to collect long-term follow-up data. Notably, AB-1005 is also now being evaluated for PD in a sham-controlled phase 2 clinical trial (REGENERATE-PD; NCT06285643), which recently began the process of randomly assigning enrolled participants in the United States in January 2025. AskBio anticipates that REGENERATE-PD will open additional sites for enrollment in the US, Germany, Poland, and the United Kingdom before the midway point of 2025.

“The FDA’s decision to grant RMAT designation to AB-1005 is exciting news for people living with PD and their loved ones,” Gustavo Pesquin, MBA, the chief executive officer of AskBio, said in a statement. “This milestone could potentially expedite the development of our important investigational gene therapy program, and it highlights our promising data and the potential of AB-1005 for patients and the medical community. We look forward to working closely with the FDA to accelerate our program.”

United Therapeutics’ Gene-Edited Kidney Xenotranspant UKidney Cleared for US Trial

February 3, 2025 — United Therapeutics’ UKidney, an investigational gene-edited porcine kidney product intended to treat end-stage renal disease (ESRD) via xenotransplant, has received clearance of an investigational new drug (IND) application from the FDA.

In light of the IND clearance, United Therapeutics intends to go forward with plans for a phase 1/2/3 clinical trial (NCT identifier pending) with the intention of supporting a biologics license application for the product. The trial will seek to recruit patients with ESRD who are ineligible for a conventional kidney transplant for medical reasons and patients with ESRD who are on a kidney transplant waitlist, but are unlikely to receive a conventional transplant within 5 years or are unlikely to survive until a human donor kidney is available. The trial is expected to perform its first xenotransplant around the middle of this year.

“Clearance of our IND for this first-ever clinical trial of a xenokidney represents a significant step forward in our relentless mission to expand the availability of transplantable organs,” Leigh Peterson, PhD, the executive vice president of product development and xenotransplantation at United Therapeutics, said in a statement. “Our goal is to increase the availability of transplantable organs to offer a therapeutic alternative to a lifetime on dialysis for a large population of patients who are unlikely to receive an allogeneic kidney transplant.”