FDA Activity Recap: August 2025 Features Papillomatosis Gene Therapy Approval, Eli-Cel Labelling Update, and More

Last month, August 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 approving Precigen’s zopapogene imadenovec-drba for recurrent respiratory papillomatosis (RRP) and lifting its clinical hold on Rocket Pharmaceuticals’ pivotal phase 2 clinical trial (NCT06092034) for RP-A501. 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 Approves Precigen’s Recurrent Respiratory Papillomatosis Gene Therapy Papzimeos

August 26, 2025 — The FDA has approved Precigen’s zopapogene imadenovec-drba (PRGN-2012), a nonreplicating adenoviral vector-based immunotherapy, for treating adults with RRP. The therapy will be marketed under the name Papzimeos.

Papzimeos, which is administered over a 12-week timeframe through 4 subcutaneous injections, 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, providing an alternative to the current standard of care for RRP, which typically involves repeated surgical interventions. The therapy was approved based on the results of a pivotal, open-label phase 1/2 clinical trial (NCT04724980). Notably, the FDA granted Papzimeosa full approval, without a requirement for a confirmatory trial to be conducted, even though Precigen had submitted the biologics license application (BLA) for the therapy via an accelerated approval pathway.

"For more than a century, since RRP was first recognized as a distinct disease, patients have had to rely on repeated surgeries to manage this relentless condition,” Helen Sabzevari, PhD, the president and CEO of Precigen, said in a statement. “Today marks a historic turning point. With the landmark FDA approval of Papzimeos and broad label, all adult RRP patients are now eligible for access to the first and only approved therapy that targets the root cause of the disease. This milestone affirms the power of our AdenoVerse platform and the exceptional capabilities of our team to rapidly advance a wholly novel therapy from discovery to approval considerably faster than industry benchmarks. We are profoundly grateful to the NIH clinicians, the FDA, and—most importantly—the patients and families who made this breakthrough possible. We look forward to swiftly delivering Papzimeos to the RRP community and ushering in a new era of treatment that targets the underlying cause of the disease rather than just managing its symptoms."

FDA Lifts Clinical Hold on Rocket’s Trial for Danon Disease Gene Therapy RP-A501

August 21, 2025 — The FDA has lifted its clinical hold on Rocket Pharmaceuticals’ pivotal phase 2 clinical trial (NCT06092034) evaluating RP-A501, an investigational adeno-associated virus serotype 9 (AAV9) vector-based gene therapy intended to treat Danon disease.

The hold was originally placed on the trial by the FDA on May 23, 2025, following the death of a patient treated in the study. The patient’s death occurred after an acute systemic infection and was associated with an unexpected serious adverse event (SAE) of clinical complications related to a capillary leak syndrome. At the time the hold was announced, a comprehensive root cause analysis was underway, with a focus on a novel immune suppression agent specific to the AAV9 Danon program that had recently been added to the gene therapy’s pretreatment regimen with the intention of reducing complement activation, a phenomenon that had been seen in some participants. Rocket stated that dosing in the trial was paused when it became aware of the SAE.

With regard to the lifting of the hold, Rocket noted that the FDA indicated the company has addressed the issues leading to the clinical hold to its satisfaction. Per the FDA’s authorization for the study’s continuation, a recalibrated dose for the gene therapy, 3.8 x 10¹³ genomic copies/kg, will be used for the next 3 patients to be treated in the study and the patients will be treated in a sequential manner with intervals of 4 weeks or greater between each treatment. Notably, 6 patients have been treated in the phase 2 study so far and RP-A501 has previously been evaluated for Danon disease in a phase 1 clinical trial (NCT03882437).

FDA Bumps Back PDUFA for REGENXBIO's MPS II Gene Therapy RGX-121

August 25, 2025 — The FDA has extended the review timeline for REGENXBIO's BLA for clemidsogene lanparvovec (RGX-121), an investigational AAV vector-based gene therapy intended to treat mucopolysaccharidosis type 2 (MPSII, also known as Hunter syndrome), setting a new Prescription Drug User Fee Act (PDUFA) goal date of February 8, 2026.

The new PDUFA date is several months later than the original PDUFA date of November 9, 2025. REGENXBIO noted that the extended timeline came after the company responded to an FDA information request by submitting longer-term clinical data for all 13 patients treated in the pivotal phase 1/2/3 CAMPSIITE clinical trial (NCT03566043). REGENXBIO pointed out that the updated data are consistent with previously submitted biomarker and neurodevelopmental findings. The new data will be presented at the International Congress of Inborn Errors of Metabolism (ICIEM), which will be held in Kyoto, Japan, from September 2 to 6, 2025.

REGENXBIO also noted that the FDA has conducted a prelicense inspection and bioresearch monitoring information inspection for RGX-121 BLA. The inspection, carried out in August 2025, yielded no observations. Furthermore, the agency has not raised safety concerns during the BLA review.

FDA Updates Labeling for bluebird's Active Cerebral Adrenoleukodystrophy Gene Therapy Eli-Cel to Reflect Risk of Hematologic Malignancy

August 11, 2025 — The FDA is requiring updated labeling for bluebird bio's elivaldogene autotemcel (eli-cel; Skysona), a gene therapy product comp of engineered autologous CD34+ hematopoietic stem cells intended to treat early, active cerebral adrenoleukodystrophy (CALD), to reflect an increased risk of hematologic malignancy following treatment with the product.

Specifically, the agency is requiring updates to the Boxed Warning, Indications and Usage, Warnings and Precautions, and Adverse Reactions – Clinical Trials Experience sections of eli-cel's prescribing information and Medication Guide. With regard to the revised Indications and Usage section, only patients without an available human leukocyte antigen (HLA)–matched donor for allogeneic hematopoietic stem cell (allo-HSC) are eligible to receive eli-cel.

“...Skysona should only be used in CALD patients without suitable alternative treatment options, given the increased risk of hematologic malignancy,” the FDA said in a press release announcing the required labeling changes. “The Limitations of Use section retains language emphasizing careful consideration of appropriateness and timing of treatment.”

FDA Gives Priority Review to BMS’s Supplemental BLA for Liso-Cel in R/R Marginal Zone Lymphoma

August 4, 2025 — Bristol Myers Squibb’s supplemental BLA (sBLA) for marketed autologous CD19-directed CAR T-cell therapy lisocabtagene maraleucel (liso-cel, marketed as Breyanzi) for marginal zone lymphoma (MZL) has been accepted by the FDA with priority review. The Prescription Drug User Fee Act goal date for the sBLA has been set for December 5, 2025.

Specifically, the sBLA is under review for adults with relapsed/refractory (R/R) MZL who have been treated with 2 or more previous lines of systemic therapy. The sBLA is supported by data from the phase 2 TRANSCEND FL clinical trial (NCT04245839).

“While initial therapy for MZL can be effective, multiple relapses over the course of several years are common, leaving patients in need of a new treatment option that can provide high, lasting response rates,” Rosanna Ricafort, the vice president and head of Late Development Program Leadership, Hematology and Cell Therapy, at BMS, said in a statement. “This FDA acceptance brings us one step closer to potentially standardizing CAR T-cell therapy as a treatment option for MZL, while building on our commitment to bring this personalized therapy to as many eligible patients as possible.”