Blog | 9/29/2025

2025 Marks Technology, Regulatory, and Disease Area Shifts in Cell and Gene Therapy

By Ned Wydysh, Vivek Mittal, Alicia Worsley, Andrew Chen, Dorian Cohen, and Wesley Liao

The cell and gene therapy (CGT) world that seemed to be hitting its stride now feels like a pendulum swinging between triumph and turbulence. As the calendar turned to 2025, leadership churn at the federal agency charged with shepherding these advanced therapies to market and a string of strategic pivots represent a clear shift in the balance of promising applications. Against the backdrop of rapid CGT innovation, this article takes stock of the high-profile events that have defined the last several months and sets the tone for what comes next—from broad questions about evidentiary standards and accelerated pathways to their knock-on effects on investors, developers, and patients.

Our team will unpack the key episodes behind the headlines and show how they thread together into a bigger picture for the CGT sector. You’ll read about how a regulator’s abrupt departure and equally abrupt return have underscored the unsettled tenor at the FDA; about the drama surrounding a landmark Duchenne Muscular Dystrophy (DMD) gene therapy that went from celebrated accelerated approval to a U.S. hold in the face of tragic safety events; and about other signals—from PDUFA extensions to in vivo cell therapy programs. You’ll see how resilience and inventiveness persist amid the headwinds: new delivery approaches, dual-targeting constructs, bold financings, and high-profile partnerships that speak to the sector’s enduring promise even as companies and investors recalibrate for a more exacting environment. These introductory observations set the stage for a deeper dive into how regulatory stability, investor confidence, and the pace of clinical development are being reshaped today to position these advanced therapies for future success.

Leadership Shake-Up and Regulatory Uncertainty

2025 brought an upheaval in FDA leadership that fueled uncertainty in the CGT sector. The key figure in this drama was Dr. Vinay Prasad, an oncologist-turned-regulator who in early 2025 headed FDA’s Center for Biologics Evaluation and Research (CBER) – the division overseeing vaccines and advanced therapies including CGTs.

Dr. Prasad had a reputation as both a strong advocate for CGT development and a stickler for robust evidence. Notably, he was skeptical of using surrogate endpoints (like biomarkers) for accelerated approval in gene therapy, favoring more concrete efficacy data. Under his watch, FDA had indeed been carefully scrutinizing CGT approvals (the Elevidys decision being a prime example). His stance raised worries that accelerated approvals for CGTs might be harder to attain or that requirements for confirmatory trials could tighten.

In late July 2025, Prasad abruptly resigned from his CBER post. Initially, little official explanation was given, but it soon emerged that his departure followed a storm of external political criticism over Elevidys and related decisions. Only 12 days later, in a stunning U-turn, HHS announced on August 9, 2025, that Prasad would return as CBER Director at the FDA’s request. This whiplash sequence – a high-profile regulator stepping down and then being reinstated two weeks later – is virtually unheard of at the agency.

The Prasad saga exacerbated a sense of regulatory volatility. Pharmaceutical media noted that his “shock FDA return reignites regulatory uncertainty” in the field. Industry observers were caught off-guard, and CGT developers’ stocks moved on these leadership headlines: shares of multiple gene therapy companies rose when Prasad’s resignation was first reported, then fell when he was reinstated, reflecting the market’s read on his perceived strictness.

From the CGT sector’s perspective, the Prasad incident signaled instability at the FDA. In fact, 2025 saw not only the CBER chief rollercoaster but also a change at the very top: a new FDA Commissioner, Dr. Marty Makary, took over around mid-2025, adding to the transitional churn.

By the end of 2025, with Prasad back at the helm, companies are hopeful that he would proceed more “incrementally,” but are nonetheless bracing for stricter evidentiary standards in areas like accelerated approval.

In parallel, the FDA’s emerging N-of-1 pathway is reshaping gene-editing approvals for ultra-rare diseases by embracing regulatory flexibility, advanced platform technologies, and patient-specific customization. This was evidenced by the six-month sprint that produced the first custom CRISPR gene-editing therapy for Kyle Patrick Muldoon, Jr., an infant with a rare metabolic disease called CPS1 deficiency. The FDA approved the treatment after a one-week review, and Kyle received it soon after. In addition, the FDA has guidance for a Platform Technology designation to facilitate such situations: once an initial gene-editing therapy is approved, a sponsor can obtain a platform-wide designation, making subsequent custom therapies using the same core editing system much faster to approve. Through these initiatives, the FDA is signaling that even “one-patient, one-drug” gene therapies can reach the clinic – a dramatic shift that promises to expand access to lifesaving treatments for ultra-rare disorders.

The Elevidys Saga: Accelerated Approval Under the Microscope

Nothing crystallized the tension between speedy approvals and safety oversight more than the drama surrounding Sarepta Therapeutics’ Elevidys, a gene therapy for Duchenne muscular dystrophy (DMD). Elevidys was initially approved under the accelerated pathway in June 2023 for non-ambulatory DMD boys, based on a surrogate endpoint (micro-dystrophin expression). In June 2024, FDA granted full approval for Elevidys in ambulatory patients (ages ≥4) after additional data. This two-tiered approval was seen as a win for patients and a testament to accelerated approval’s value, given DMD’s dire prognosis.

However, by 2025 a series of tragic events led to an unprecedented FDA intervention that shook the CGT sector. In March and June 2025, two teenage DMD patients (non-ambulatory) who received Elevidys commercially died from acute liver failure. Their deaths raised alarms about the therapy’s safety in sicker patients. Sarepta voluntarily halted Elevidys use in non-ambulatory patients after the second death, but continued offering it to ambulatory children (who appeared to tolerate therapy better). Then in July 2025, a third fatality occurred: a 51-year-old patient in a Sarepta clinical trial for limb-girdle muscular dystrophy (LGMD), who received an experimental gene therapy using the same AAVrh74 vector as Elevidys, also died of acute liver failure.

Faced with these three related deaths, the FDA took extraordinary action on July 18, 2025:

It requested Sarepta suspend all Elevidys distribution in the U.S. and placed a clinical hold on all trials of Sarepta gene therapies using the AAVrh74 vector.
The agency simultaneously revoked Sarepta’s “platform technology” designation for the AAVrh74 vector, which rescinded certain development conveniences that had been granted on the premise of platform safety.
FDA publicly cited an “unreasonable and significant risk” to patients, saying it “will not allow products whose harms are greater than benefits”. Dr. Vinay Prasad emphasized that patient safety was paramount and defended the decision to halt trials and withdraw the broader vector platform until risks could be better understood.

By July 22, 2025, Sarepta halted all Elevidys shipments, including those for ambulatory patients after the FDA requested a pause on all shipments due to an investigation into a fourth death involving an 8-year-old ambulatory DMD patient from Brazil who received Elevidys. The company agreed to stop new infusions, allowing time to work with FDA on safety mitigations. After intensive data review and negotiation, FDA lifted the blanket hold on July 28, permitting Sarepta to resume Elevidys for ambulatory patients only. Additional safeguards were implemented: a new Black Box Warning for acute liver injury was added to Elevidys’s label and a stricter risk mitigation plan put in place. The non-ambulatory DMD indication remained off the label (effectively withdrawing the accelerated approval for that subgroup until more is known). FDA also kept the LGMD gene therapy trials on hold as of that time.

The Elevidys episode has had far-reaching implications:

It was a stress-test of the accelerated approval paradigm for CGT. Critics of accelerated approval argue that allowing early market entry on limited data may expose patients to unforeseen risks.
Regulatory uncertainty increased for CGT developers. Companies saw that FDA was willing to change course on an already-approved gene therapy and confront a sponsor publicly.
Investor sentiment toward gene therapy companies became more bearish. Shares of several CGT developers dipped amid the Elevidys controversy, as investors contemplated stricter safety oversight and potential delays for other programs. Sarepta itself, facing the Elevidys setback, announced a major restructuring and cost-cutting effort.. This pullback underscored how regulatory hiccups can directly translate into reduced R&D investment – a clear indicator of shaken confidence.

CGT Sector Momentum Meets More Regulatory Caution

PDUFA Extensions: The FDA has also demonstrated willingness to extend review timelines to gather more data on CGTs before approval. For instance, Regenxbio announced in August 2025 that FDA had extended the BLA review for RGX-121 (a gene therapy for Hunter syndrome) by three months, moving the PDUFA target from Nov 2025 to Feb 2026. The agency had requested 12-month follow-up data from all patients, which the company promptly submitted, triggering the standard extension to allow the FDA to review the new submission. Notably, Regenxbio reported FDA’s pre-license manufacturing inspection found no observations and no safety concerns – again indicating the delay was to vet durability of efficacy rather than address an acute problem. Such PDUFA deferrals have become more frequent for CGTs, as regulators often seek longer-term outcomes (e.g. sustained biomarker reduction, durable functional gains) before green-lighting one-time treatments. Industry analysts have observed a pattern of FDA postponements in this arena, as gene therapy reviews continue to raise extra questions and data requests. While extensions are preferable to outright rejection, they contribute to uncertainty in launch timelines and can strain small companies’ finances.

Challenging Time for Cell Therapy

This climate of regulatory caution has amplified pressure on cell therapy, which is already experiencing a wave of strategic retreats as sponsors recalibrate portfolios. The cell therapy sector is facing a wave of strategic pivots, reflecting a broader recalibration across the industry:

AstraZeneca announced the discontinuation of three cell therapy programs, including NT-125—Neogene Therapeutics’ lead neoantigen-targeted TCR candidate acquired in a $200MM deal. The company cited “strategic portfolio prioritization” as the reason, choosing instead to focus on broader applications of Neogene’s TCR platform and next-gen CAR-Ts for multiple myeloma.
Genentech decided to terminate its $2B collaboration with Adaptive Biotechnologies, a partnership that began in 2019 to develop personalized cancer therapies using Adaptive’s TruTCR platform. The collaboration focused on identifying TCRs that target specific antigens in a patient’s tumor, with Adaptive receiving $300MM in upfront payments. The termination, effective February 2026, was announced as part of Genentech’s broader R&D restructuring. Adaptive, meanwhile, is shifting its focus toward autoimmune disease applications and advancing its digital TCR-antigen mapping capabilities.
Adicet Bio also made a sharp pivot, cutting 30% of its workforce and shelving its ADI-270 T-cell therapy for renal cell carcinoma, despite promising preclinical data. The company is now prioritizing autoimmune indications, including lupus nephritis, where its AD1-001 candidate recently received FDA fast-track designation.
Capricor Therapeutics faced a regulatory setback when the FDA rejected its cell therapy deramiocel for Duchenne muscular dystrophy-related cardiomyopathy. The agency cited insufficient evidence of efficacy and gaps in manufacturing controls, despite Capricor’s submission being backed by long-term data from an open-label extension study. The rejection came amid leadership changes at the FDA, raising questions about shifting regulatory standards.

Collectively, these developments underscore the challenges facing cell therapy developers—from scientific complexity and commercial viability to evolving regulatory expectations—prompting many to rethink their pipelines and pivot toward more promising or tractable therapeutic areas.

Resilience and Innovation Unfolding Amid CGT Headwinds

Despite headwinds challenging the CGT sector, the past year has brought a wave of promising developments that underscore the field’s resilience and continued innovation. These breakthroughs not only signal scientific progress but also reflect growing investor confidence and strategic momentum across the industry.

One exciting area of advancement has been in vivo CAR-T therapy, which bypasses the need for ex vivo cell manipulation by reprogramming T cells directly within the patient’s body. This approach could offer a more scalable, off-the-shelf alternative to traditional CAR-T therapies, potentially reducing manufacturing costs and improving accessibility.

Active Deals Arena: In August, AbbVie completed the $2.1B acquisition of Capstan Therapeutics, a clinical-stage biotechnology company dedicated to advancing in vivo engineering of cells through RNA delivery using targeted lipid nanoparticles (tLNPs). Capstan's lead asset CPTX2309, currently in Phase 1 for the treatment of B cell-mediated autoimmune diseases, is a tLNP that generates CD19-specific, CD8+ in vivo CAR-T cells. This deal highlights the growing belief that in vivo CAR-T could become a first-in-class modality with broad applications
Encouraging Clinical Data Emerging: Following AstraZeneca’s $1B acquisition of EsoBiotec in May, the companies released early but promising Phase 1 clinical data for in vivo CAR-T therapy in multiple myeloma patients. Among four patients who received the therapy (ESO-T01), two of the patients saw their cancer resolve completely. All the patients experienced side effects, including cytokine release syndrome, neutropenia, and lung infections. While early evidence is encouraging, the investigators of the trial highlight that “a larger cohort and longer follow-up are needed to further look into the persistence of in vivo-produced CAR T cells and their efficacy, and a randomised controlled design is required for more convincing results.”

In addition to the growing excitement around in vivo CAR-T therapies, traditional ex vivo CAR-T approaches continue to evolve, with promising innovations that could reshape treatment paradigms for hematologic malignancies. A standout example is Johnson & Johnson’s investigational dual-targeting CAR-T therapy, JNJ-4496, which binds to both CD19 and CD20 antigens. This bispecific design aims to overcome resistance mechanisms that often limit the durability of single-antigen CAR-T therapies. Early data from a Phase 1b study in relapsed or refractory large B-cell lymphoma showed that among patients who had received only one prior line of therapy, the objective response rate (ORR) was 100%, with a complete response rate (CRR) of 80%. Even among those with two or more prior lines of therapy, the ORR remained high at 92%, with a CRR of 75%.

These results suggest that dual-targeting CAR-T therapies like JNJ-4496 could offer deeper and more durable remissions, especially for patients who have limited options after failing standard lines of treatments. This program also underscores the broader momentum in CAR-T innovation, not just in delivery methods like in vivo platforms, but also in targeting strategies and molecular engineering.

Beyond the buzz around in vivo CAR-T therapies, other positive developments in the CGT landscape offer reassuring signals on the continued interest and innovation in CGT modalities. Eli Lilly’s acquisition of Verve Therapeutics for up to $1.3 billion marks a significant move into the gene editing space for cardiometabolic disease. Verve’s lead candidate, VERVE-102, is an in vivo base editing therapy targeting PCSK9, designed to offer a one-time treatment for heterozygous familial hypercholesterolemia and other high-risk cardiovascular populations. As Lilly expands beyond blockbuster diabetes and obesity franchises, the acquisition reflects the potential of gene editing to shift chronic disease management towards curative paradigms.

Kriya Therapeutics also had a successful year despite pressure on gene therapy investment, closing a $320MM series D round in one of the largest private biotech financings of 2025 to date. Kriya is developing a suite of gene therapy assets targeting chronic conditions including geographic atrophy, thyroid eye disease, type 1 diabetes, and metabolic-associated steatohepatitis (MASH). Despite regulatory and macroeconomic headwinds, Kriya’s raise demonstrates that investors still have confidence in promising CGT firms to navigate biotech uncertainty.

The science behind gene therapies continues to progress with positive clinical readouts as 4D Molecular Therapeutics (4DMT) reported compelling 60-week data from its SPECTRA Phase 2a trial evaluating anti-VEGF gene therapy 4D-150 in diabetic macular edema (DME). The therapy, delivered via a single intravitreal injection, showed a 78% reduction in treatment burden compared to standard-of-care aflibercept, with sustained gains in visual acuity and anatomical improvements. Regulatory alignment with both the FDA and EMA for a single Phase 3 trial further de-risks the path to approval, paving the way for continued gene therapy clinical advancement in ophthalmic conditions.

Looking Forward

The last 9 months have produced a significant number of high-profile events representing shifts in how CGTs are regulated, which technologies are driving investment activity, and disease areas where they are being developed. Given the rapid evolution of the field, we expect the remainder of 2025 will deliver continued progress toward making these approaches a reality for patients with high unmet need conditions. Our team is excited to keep tracking the field’s advancement and advising our clients on how to best position themselves to take advantage of the tremendous promise of these advanced therapies.