Industry Insights: A CAR-T safety halt for Novartis and a first gene therapy approval for Ultragenyx

Novartis paused eight cell therapy trials in autoimmune and neurological disease after three deaths [1]

Novartis paused eight clinical trials of rap-cel, an experimental CAR-T cell therapy targeting autoimmune and neurological disorders, after three patients died. The halt, implemented on August 24, 2026, followed three cases of immune effector cell-associated hemophagocytic syndrome, a severe, life-threatening immune reaction. Affected trials covered inflammatory conditions including lupus, rheumatoid arthritis, and vasculitis, and neuromuscular disorders including multiple sclerosis and myasthenia gravis; Novartis's lymphoma and leukemia trials were unaffected. The company described the reaction as a known, potentially life-threatening risk of CAR-T therapy and was working with independent safety boards to review the deaths. Bristol Myers separately paused studies of a rival CAR-T therapy, zola-cel, out of "an abundance of caution".

Oak Hill Bio dosed the first participant in the Phase 3 BEACON trial of rugonersen in Angelman syndrome [2]

Oak Hill Bio announced that the first participant was dosed in BEACON, a pivotal Phase 3 trial of rugonersen, an investigational antisense oligonucleotide (ASO) for Angelman syndrome, a neurodevelopmental disorder caused by disruption of the UBE3A gene. Rugonersen, originally developed by Roche, is designed to restore UBE3A expression. BEACON is a global, randomized, double-blind, sham-controlled trial enrolling up to 165 participants aged 1–50 years, randomized 1:1 to sham or 120 mg rugonersen by intrathecal injection every 12 weeks; the primary endpoint is change from baseline in Bayley Scales cognition or expressive communication at 56 weeks. The prior Phase 1 TANGELO trial showed dose-dependent partial normalization of electroencephalogram delta power. Topline results are expected in early 2029.

Oak Hill Bio dosed the first participant in the Phase 3 BEACON trial of rugonersen in Angelman syndrome; Clinical Trials and Research. Credit: www.magnific.com

Ultragenyx secured the first US FDA approval for a gene therapy in glycogen storage disease type Ia [3]

Ultragenyx Pharmaceutical announced that the US FDA granted accelerated approval to Genglycos, the first gene therapy for glycogen storage disease type Ia (GSDIa, or von Gierke disease), in adult and pediatric patients aged eight years and older. GSDIa results from deficiency of an enzyme that releases hepatic glucose, causing life-threatening hypoglycemia and requiring continual raw cornstarch intake. The disorder is estimated to affect several thousand patients. Genglycos delivers a functional copy of the G6PC gene, restoring G6Pase activity and reducing cornstarch reliance. Approval rested on a 48-week, placebo-controlled Phase 3 trial in which treated patients showed reduced cornstarch requirements versus placebo, a surrogate endpoint; the FDA required confirmatory data, and the company agreed to provide two years of safety and efficacy data. The US per-patient list price was reported to be around $2.7M.

Ultragenyx secured the first US FDA approval for a gene therapy in glycogen storage disease type Ia; Regulatory Changes and Updates. Credit: www.ultragenyx.com

REGENXBIO reported an FDA clinical hold on its RGX-121 gene therapy for Hunter syndrome [4]

REGENXBIO provided a regulatory update on RGX-121 (clemidsogene lanparvovec), an investigational AAV gene therapy for mucopolysaccharidosis type II (MPS II, Hunter syndrome). The FDA placed a clinical hold after expanded MRI monitoring identified asymptomatic spine findings, such as small nodules or cystic masses, in five participants dosed intracisternally or intraventricularly 3–6 years earlier in the CAMPSIITE study. Investigators judged the findings nonserious and likely benign, with no brain lesions detected; all five continued to show neurocognitive and neurobehavioral stability or improvement. The company did not expect to resubmit the Biologics License Application (BLA) in the near term and, with partner NS Pharma, planned further imaging and follow-up while awaiting the full clinical hold letter.

REGENXBIO reported an FDA clinical hold on its RGX-121 gene therapy for Hunter syndrome; Regulatory Changes and Updates. Credit: www.prnewswire.com

Capricor's Deramiocel review received a 3-month PDUFA extension in Duchenne muscular dystrophy [5]

Capricor Therapeutics announced that the FDA extended the PDUFA target action date for its BLA for Deramiocel (CAP-1002), an investigational allogeneic cardiosphere-derived cell therapy for Duchenne muscular dystrophy (DMD), from August 22 to November 22, 2026. Following the July 2026 Advisory Committee meeting, Capricor amended the BLA with 24-month open-label extension data from the pivotal Phase 3 HOPE-3 study and additional robustness analyses, supporting a refined proposed indication focused on upper limb function, the study's primary endpoint. The FDA's Center for Biologics Evaluation and Research classified the submission as a major amendment, citing significant unmet need, and extended the review by 3 months. HOPE-3 met its primary endpoint, demonstrating a statistically significant upper limb benefit.

Kyverna's miv-cel received an FDA regenerative medicine advanced therapy designation in non-active secondary progressive multiple sclerosis [6]

Kyverna Therapeutics reported that the FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to miv-cel (mivocabtagene autoleucel) in non-active secondary progressive multiple sclerosis (naSPMS), based on clinical data from investigator-initiated trials at Stanford University and the University of California, San Francisco. Miv-cel is a fully human, autologous, CD19-targeting CAR-T therapy with CD28 co-stimulation under investigation for B cell-driven autoimmune diseases, in which a single dose is intended to achieve deep B cell depletion and immune reset. The company noted this as miv-cel's third RMAT indication. Kyverna remained on track to complete a rolling BLA in stiff person syndrome in Q4 2026, with 12-month KYSA-8 topline data expected in Q3 2026 and a progressive multiple sclerosis strategy update anticipated by early 2027.

Cellenkos received FDA Fast Track designation for CK0803, a cord blood-derived regulatory T cell therapy, in amyotrophic lateral sclerosis [7]

Cellenkos announced that the FDA granted Fast Track designation to CK0803, an allogeneic, cord blood-derived regulatory T cell (Treg) therapy, for amyotrophic lateral sclerosis (ALS), which the company described as the first Treg product to receive the designation in ALS. CK0803 is engineered to home to inflamed microglia via the CXCR3/CXCL10 axis, aiming to interrupt the inflammation-injury cycle and restore neuroimmune homeostasis. The designation, granted under the company's IND application, followed early clinical evaluations in which CK0803 was associated with an approximately 60% decrease in neurofilament light chain and a 200% increase in plasma interleukin-10. Cellenkos framed the designation as enabling closer FDA engagement in a disease with median survival of 2–3 years from symptom onset.

PTC Therapeutics agreed to acquire Sangamo's late-stage ST-920 gene therapy for Fabry disease [8]

PTC Therapeutics announced that it was selected as the winning bidder to acquire ST-920, a one-time AAV gene therapy for Fabry disease, from Sangamo Therapeutics in a bankruptcy auction. Terms comprised $111M upfront and up to $100M in contingent milestones, with closing expected in late Q3 or early Q4 2026, subject to bankruptcy court approval and customary conditions. ST-920 drives expression of the deficient α-Gal A enzyme and holds RMAT, Orphan Drug, and Fast Track designations. In the Phase 1/2 STAAR study, it produced a positive mean annualized estimated glomerular filtration rate slope at 52 weeks, with all enrolled patients withdrawn from enzyme replacement therapy. PTC expected to complete a rolling BLA for accelerated approval in Q4 2026.

PTC Therapeutics agreed to acquire Sangamo's late-stage ST-920 gene therapy for Fabry disease; Market Trends. Credit: www.magnific.com

Bristol Myers Squibb ended its CAR-T manufacturing agreement with Cellares, which announced about 100 layoffs [9]

Bristol Myers Squibb ended its manufacturing partnership with the cell therapy company Cellares after determining that the Cell Shuttle platform could not produce its CAR-T therapy Breyanzi at commercial scale, a company spokesperson told Reuters. The 2024 agreement, worth up to $380M, had reserved manufacturing capacity across the US, the European Union, and Japan for CAR-T therapies; the decision applies only to Breyanzi and its approved process. Cellares disputed the characterization, stating that Cell Shuttle had already produced a GMP-compliant cell therapy in an FDA-regulated clinical program. The company disclosed plans to lay off about 100 employees at its South San Francisco facility on October 20. Breyanzi generated $1.36B in 2025 sales.

Sail Biomedicines and Johnson & Johnson formed a strategic collaboration to develop in vivo CAR-T therapies [10]

Sail Biomedicines, a Flagship Pioneering company, announced a strategic collaboration with Johnson & Johnson to develop in vivo CAR-T therapies for immune-mediated diseases. The collaboration pairs Sail's eRNA™ and targeted nanoparticle platform, which coordinates RNA construct design, cell targeting, and expression duration, with Johnson & Johnson's development, manufacturing, and commercialization capabilities. The companies planned to advance Sail's lead in vivo CAR-T program in autoimmune disease and to pursue additional programs aimed at durable disease remission through immune system reset. Under the terms, Johnson & Johnson would make initial payments of $785M, including a $465M equity investment, plus $140M tied to development milestones; an exclusive option to acquire Sail would trigger a further $2.58B payment.

Kyverna Therapeutics and ElevateBio signed a commercial manufacturing and supply agreement for CD19-directed CAR-T therapy [11]

St. Jude researchers reported that Regnase-1 knockout improved CAR-T activity against osteosarcoma in preclinical models [12]

Scientists at St. Jude Children's Research Hospital reported that deleting the Regnase-1 gene from CAR-T cells improved their activity against relapsed osteosarcoma in preclinical models, in work published in Cell Reports Medicine. Regnase-1 normally restrains immune function; its knockout enhanced tumor control and prevented lung metastasis. In mouse models, nearly all animals treated with human Regnase-1 knockout CAR-T cells targeting B7-H3 survived, whereas untreated mice and those given conventional CAR-T cells succumbed; survivors later rejected re-implanted tumors, indicating durable responses. The modified cells also remodeled the tumor microenvironment, recruiting additional immune cells, raising immune-activating signals, and reducing immunosuppressive populations. The team reported plans to develop an early-phase clinical trial through its pediatric immuno-oncology center.

Stanford researchers engineered tissue-resident natural killer cells to infiltrate solid tumors in preclinical studies [13]

Researchers at Stanford Medicine reported a method to convert circulating natural killer (NK) cells into a cytotoxic, tissue-resident form capable of infiltrating solid tumors, published in Science Translational Medicine. Brief exposure to short-lived epithelial tumor cells delivering a controlled burst of TGF-β, together with direct cell contact, generated tissue-resident NK cells expressing CD39, perforin, and granzyme A. In mouse models of human melanoma and head and neck squamous cell carcinoma, the modified cells slowed tumor growth, with the strongest effect when combined with the antibody cetuximab, without apparent adverse effects. Because NK cells rarely trigger alloreactivity, the approach could support an off-the-shelf therapy; roughly 20 doses were generated per donor. A Phase 1 trial is planned, pending FDA clearance.

Abi Pinchbeck, Commissioning Editor, Cell & Gene Therapy Insights, has extensive experience in advanced therapy journal publishing. Abi's focus is on progressing the field by facilitating and disseminating high-impact, open access content covering novel and existing cell and gene therapies. Abi works closely with academic scientists and industry professionals to publish cutting-edge original research, expert reviews, and multimedia content with a translational and interdisciplinary focus. Abi's key aim is to explore the latest advances in cell and gene therapy R&D, clinical development, manufacturing, and commercialization. In addition to Abi's editorial responsibilities, she maintains a strong network of experts across the biotech and pharma industries, staying up to date with emerging trends and breakthroughs in advanced therapies.

References

1. Novartis pauses trials of experimental cell therapy after three deaths. Reuters 2026; Sep 1.

2. Oak Hill Bio. Oak Hill Bio announces dosing of first participant in BEACON Phase 3 clinical trial of rugonersen in Angelman syndrome. Jul 28, 2026.

3. Sneha SK, Ananthan P. Ultragenyx's gene therapy wins first FDA approval for rare metabolic disorder. Reuters, Aug 19, 2026.

4. REGENXBIO Inc. REGENXBIO announces regulatory update on RGX-121 for MPS II. PR Newswire, Aug 24, 2026.

5. Capricor Therapeutics. Capricor Therapeutics announces extension of PDUFA target action date as FDA continues review of Deramiocel BLA. Aug 24, 2026.

6. Kyverna Therapeutics. Kyverna Therapeutics reports pipeline progress and second quarter 2026 financial results. Aug 11, 2026.

7. Cellenkos, Inc. Cellenkos receives FDA Fast Track designation for CK0803 in amyotrophic lateral sclerosis (ALS). PR Newswire, Aug 25, 2026.

8. PTC Therapeutics, Inc. PTC to expand rare disease portfolio with acquisition of BLA-stage ST-920 Fabry disease program. PR Newswire, Aug 12, 2026.

9. Bristol Myers ends blood cancer drug deal with cell therapy maker Cellares. Reuters, Aug 26, 2026.

10. Sail Biomedicines. Sail Biomedicines announces strategic collaboration to develop new class of medicines for in vivo CAR-T. Business Wire, Jul 28, 2026.

11. Kyverna Therapeutics and ElevateBio Enter into Commercial Manufacturing and Supply Agreement for Miv-cel. ElevateBio, Jul 27, 2026.

12. St. Jude Children's Research Hospital. Removing immune 'brake' improves CAR-T cell therapy for osteosarcoma. Aug 25, 2026.

13. Stanford Medicine. Supercharged 'natural killer' cells could be a powerful new cancer weapon. ScienceDaily, Aug 25, 2026.