FDA Activity Recap: November 2025 Features SMA Approval, Boxed Warning for Elevidys, and More

Last month, November 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 Novartis’ intrathecally-delivered spinal muscular atrophy gene therapy onasemnogene abeparvovec-brve (also known as OAV101 IT and adding a boxed warning to the prescribing information for Sarepta Therapeutics' Duchenne muscular dystrophy (DMD) gene therapy delandistrogene moxeparvovec-rokl (marketed as Elevidys). 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 Itvisma, a New Intrathecal Route for Novartis’ SMA Gene Therapy

November 25, 2025 — The FDA has approved Novartis’ onasemnogene abeparvovec-brve, an intrathecally-delivered version of the separately marketed gene therapy onasemnogene abeparvovec (Zolgensma), for the treatment of SMA in people 2 years of age and older who have a confirmed mutation in the survival motor neuron 1 (SMN1) gene. It is to be marketed under the name Itvisma.

According to Novartis, it is the first gene replacement therapy to have been approved “for this broad population.” It uses a fixed dose that does not require adjustment for age or weight, and is intended as a 1-time treatment.

“The FDA’s approval of intrathecal onasemnogene abeparvovec is a game-changing advance, expanding the use of transformational gene replacement therapy for SMA across age groups,” John W. Day, MD, PhD, a professor of neurology and pediatrics, the director of the Division of Neuromuscular Medicine at Stanford University School of Medicine, and codirector of Stanford’s Neuro IGNITE Center, said in a statement. “This achievement is not only a significant step forward for SMA – it also signals new possibilities for the broader field of neurological disorders and genetic medicine.”

Sarepta's Elevidys Gets Boxed Warning for ALI and ALF

November 25, 2025 — The FDA has updated the prescribing information for Sarepta Therapeutics' DMD adeno-associated virus (AAV) vector-based gene therapy delandistrogene moxeparvovec-rokl (marketed as Elevidys). Among the several changes are the addition of a boxed warning for risk of acute serious liver injury (ALI) and acute liver failure (ALF), removal of eligibility for nonambulatory patients, and expanded guidance for prescribers.

Specifically, the expanded guidance includes a modified oral corticosteroids regimen for before and after treatment, as well as recommendations for weekly enhanced monitoring in the 3 months after treatment. Sarepta also noted that it intends to evaluate an sirolimus immunosuppressive regimen aimed at reducing ALI and ALF risks with the hope of aligning with the FDA on a plan to allow for a return of eligibility of nonambulatory patients. In addition to the aforementioned changes to the prescribing information, the FDA also added a new Warnings & Precaution for heightened susceptibility to serious infections caused by immunosuppression.

“We want to thank the FDA for their thorough and collaborative review. Completion of the safety labeling change for Elevidys will ensure that families and healthcare professionals have clear information, supported by a Medication Guide, to help understand these updates and guide treatment decisions,” Louise Rodino-Klapac, PhD, the president of research & development and technical operations at Sarepta, said in a statement.

Trial for Bladder Cancer Gene Therapy Detalimogene Changes End Point Based on FDA Discussions

November 19, 2025 — enGene's detalimogene voraplasmid (also known as detalimogene, and previously referred to as EG-70), an investigational nonviral immuno-oncology gene therapy being evaluated for the treatment of high-risk bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle-invasive bladder cancer (NMIBC) with carcinoma in situ, has brought about a 62% complete response rate (CRR) at 6 months posttreatment, according to updated data from the phase 1/2 LEGEND clinical trial (NCT04752722).

Alongside the data update, enGene reported that LEGEND’s primary end point will change from landmark 12-month CR rate to CR rate at any time and that duration of response (DOR) for patients in CR has become a key secondary end point. The company noted that this move came after discussions with the FDA and that the new primary end point is consistent with other FDA-registered programs in recent times. Furthermore, enGene stated that it plans to discuss a statistical analysis plan for which patients are to be included in the final efficacy evaluable population with the FDA. enGene anticipates that a data update on the trial’s pivotal cohort will be announced in the second half of next year and expects to submit a biologics license application (BLA) in the same window of time.

“We are highly encouraged with the preliminary data from our LEGEND study, which support our planned BLA filing,” Ron Cooper, BSc, the president and CEO of enGene, added to the statement. “Based on the emerging clinical profile and detalimogene’s differentiated ease of use, we continue to believe there is a substantial commercial opportunity for detalimogene if approved.”

PreBLA Meeting With FDA Sinks uniQure’s Hopes for Approval of Huntington Disease Gene Therapy AMT-130 Based Primarily on Phase 1/2 Data

November 4, 2025 — uniQure has announced that based on feedback it received during a recent preBLA meeting with the FDA, it no longer believes that the agency will find data from phase 1/2 studies compared to an external control sufficient to support a BLA for AMT-130, an AAV vector-based gene therapy intended to treat Huntington disease (HD).

uniQure pointed out that this stands in contrast to its previous communications with the FDA in several Type B meetings, in which the agency had previously indicated alignment with uniQure’s plan to submit a BLA based primarily on phase 1/2 data. Although, the company noted that final minutes of the preBLA meeting have not yet become available, but are expected to be received within 30 days of the meeting. uniQure stated its intent to continue interaction with the FDA with the intent of finding a path for a “timely accelerated approval” of the gene therapy product. At the moment, however, the company stated that its expected timeframe for a BLA submission is unclear. Alongside its ongoing interactions with the FDA, uniQure plans to advance discussions with regulatory bodies for countries other than the United States.

“We are surprised by the FDA’s feedback at the recent preBLA meeting, which is a drastic change from the guidance the FDA provided in November 2024 that data from the ongoing phase 1/2 studies, compared to a natural history external control, may serve as the primary basis for a BLA submission under the accelerated approval pathway,” Matt Kapusta, MBA, the chief executive officer of uniQure, said in a statement. “This news is unexpected, and we are truly disappointed for people living with HD, who have no disease-modifying treatment options for this devastating disease. We strongly believe that AMT-130 has the potential to bring substantial benefit to patients, and we remain fully committed to working with the FDA to determine the best path forward to rapidly bring AMT-130 to patients and their families in the US.”