Lenmeldy (atidarsagene autotemcel) / GSK, Kyowa Kirin - LARVOL DELTA

Rare Sertoli cell tumor in a patient with metachromatic leukodystrophy treated with atidarsagene autotemcel (ESPE 2026) - No abstract available

Clinical • Metabolic Disorders • Oncology

First prospective newborn screening for metachromatic leukodystrophy enables presymptomatic intervention (SSIEM 2026) - "Two infants underwent autologous hematopoietic stem cell gene therapy with atidarsagene autotemcel at 12 months of age and showed no unexpected adverse events; both continue to develop age-appropriately...Early diagnosis enabled timely access to disease-modifying therapy and risk-adapted management. These findings support the feasibility and clinical value of introducing MLD newborn screening into routine neonatal care."

Clinical • Bone Marrow Transplantation • Gene Therapies • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

European expert recommendations for comprehensive pre-treatment, treatment-phase and post-treatment care of patients with metachromatic leukodystrophy treated with autologous haematopoietic stem and progenitor cell gene therapy. (PubMed, Eur J Paediatr Neurol) - "These European expert recommendations provide a practical framework for standardized care of children treated with HSPC-GT for MLD. Implementation across qualified treatment centres may improve clinical consistency, facilitate real-world data collection, and support sustainable delivery of gene therapy programmes. By detailing the comprehensive monitoring and follow-up required, including assessments beyond current standards of care, this work highlights the resource-intensive nature of gene therapy. It also provides a framework for the multidisciplinary care efforts needed to support planning and appropriate reimbursement by health authorities."

Journal • CNS Disorders • Gene Therapies • Metabolic Disorders

OTL-200-11: OTL-200 Long Term Insertional Oncogenesis Study (clinicaltrialsregister.eu) - P4 | N=5 | Not yet recruiting | Sponsor: Orchard Therapeutics (Europe) Limited

New P4 trial • Metabolic Disorders • Oncology

BIOLOGICAL PROPERTIES AND CLONALITY OF ENGINEERED HEMATOPOIETIC STEM/PROGENITOR CELLS PERSISTING LONG-TERM AFTER GENE THERAPY (EHA 2026) - "Aims We are studying the functional features, clonality and maintenance of stemness properties of LV-transduced HSC in long-term GT treated (LT-GT) patients with Wiskott-Aldrich Syndrome (WAS, n=6 treated with etuvetidigene autotemcel) and Metachromatic Leukodystrophy (MLD, n=10 treated with atidarsagene autotemcel) reaching a follow-up of >8 years post-GT...Finally, scRNAseq data suggest that primitive HSC from LT-GT patients express molecular signatures associated with stemness and biological features in line with HD HSPC . Overall, this study will shed light on human engineered HSC that enable maintenance a functional and safe long-term graft."

Gene therapy • Gene Therapies • Immunology • Metabolic Disorders • Primary Immunodeficiency

Disease severity and rate of progression impact ex-vivo gene therapy for Childhood Cerebral Adrenoleukodystrophy and Metachromatic Leukodystrophy: a review of the literature (ASGCT 2026) - P1/2, P2, P2/3, P3 | "For both disorders the FDA has approved ex-vivo lentiviral gene therapy: elivaldogene autotemcel (eli-cel; lentiviral vector carrying ABCD1 cDNA under a MNDU3 promoter-enhancer) and atidarsagene autotemcel (arsa-cel; lentiviral vector carrying ARSA cDNA under PGK promoter)...Results Adrenoleukodystrophy In the eli-cel trials 67 CCALD patients were treated (32 in ALD-102 with cyclophosphamide/busulfan conditioning and 35 in ALD-104 with fludarabine/busulfan conditioning)...As hematological malignancies were seen with eli-cel but not arsa-cel, treatment with eli-cel should be limited to CCALD patients who do not have a suitably matched donor available for allogeneic HSCT. AEs related to conditioning and disease were important contributors to overall safety in both trials."

Gene therapy • Preclinical • Review • Acute Myelogenous Leukemia • Alzheimer's Disease • Bone Marrow Transplantation • CNS Disorders • Cognitive Disorders • Developmental Disorders • Gene Therapies • Genetic Disorders • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Metabolic Disorders • Myelodysplastic Syndrome

PRICE ANALYSIS OF GENE THERAPIES AUTHORIZED BY THE U.S. FOOD AND DRUG ADMINISTRATION (ISPOR 2026) - "The inflation-adjusted WAC (adj-WAC) ranged from $253,121 (revakinagene taroretcel) to $4,395,213 (atidarsagene autotemcel)...Tisagenlecleucel had different prices for two indications and onasemnogene abeparvovec for two routes of administration/patient populations... When adjusted for inflation, prices remained relatively constant over time. Prices varied depending on therapeutic class, patient population, and duration of therapy. Gene therapies had similar WAC and ASP."

Gene therapy • Gene Therapies

GONADAL TOXICITY AND PREMATURE OVARIAN INSUFFICIENCY AFTER HEMATOPOIETIC STEM CELL GENE-THERAPY IN FEMALE PATIENTS WITH METACHROMATIC LEUKODYSTROPHY (EBMT 2026) - "Atidarsagene autotemcel (arsa-cel) is an ex vivo autologous hematopoietic stem-cell gene therapy and it is infused intravenously following single agent busulfan conditioning. In our analysis POI is a frequent adverse effect associated with busulfan, consistent with previous reports. Sub-myeloablative exposure does not appear reducing the incidence of gonadal dysfunction compared with myeloablative regimen. Longitudinal hormonal assessments demonstrate early impairment of ovarian reserve, and the need to offer fertility preservation before arsa-cel and to initiate HRT when indicated."

Clinical • Gene therapy • Endocrine Cancer • Endocrine Disorders • Gene Therapies • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • Women's Health

LONG-TERM CLINICAL OUTCOMES OF ATIDARSAGENE AUTOTEMCEL, AUTOLOGOUS HEMATOPOIETIC STEM CELL GENE THERAPY (HSC-GT) FOR EARLY-ONSET METACHROMATIC LEUKODYSTROPHY, WITH UP TO 13 YEARS OF FOLLOW-UP (EBMT 2026) - P1/2, P2, P3 | "With up to 13 years of follow-up, arsa-cel continues to show a favourable benefit–risk profile, exhibiting a durable effect in slowing progression and preventing severe motor and cognitive impairment in most treated patients."

Clinical • Clinical data • Gene therapy • Alzheimer's Disease • Cardiovascular • Cognitive Disorders • Gene Therapies • Metabolic Disorders

GALLBLADDER ABNORMALITIES IN METACHROMATIC LEUKODYSTROPHY: PRELIMINARY ANALYSIS IN PATIENTS TREATED WITH HEMATOPOIETIC STEM CELL GENE THERAPY AND UNTREATED PATIENTS (EBMT 2026) - "Atidarsagene autotemcel (arsa-cel), an autologous transplantation of CD34+ cells transduced ex vivo with a lentiviral vector encoding the ARSA gene, represents the only approved treatment for pre-symptomatic late-infantile and early-juvenile MLD, or early-symptomatic early-juvenile MLD forms... Our analysis confirms early and frequent gallbladder involvement across all MLD forms. Gallbladder wall thickening emerged as the earliest alteration and may represent the first precursor to more complex abnormalities such as polyps. The detection of ultrasound abnormalities as well as cases of cholecystectomy in patients before neurological symptom onset—including those with late-onset forms— suggests that visceral involvement may serve as an early diagnostic disease indicator."

Clinical • Gene therapy • CNS Disorders • Gene Therapies • Metabolic Disorders • CD34

A CASE OF LACK OF ENGRAFTMENT OF GENE-CORRECTED CELLS AFTER LENTIVIRAL HEMATOPOIETIC STEM CELL GENE THERAPY FOR METACHROMATIC LEUKODYSTROPHY: AN INTEGRATED CLINICAL AND IMMUNOLOGICAL INVESTIGATION (EBMT 2026) - "Background: Atidarsagene autotemcel (arsa-cel) is an autologous lentiviral haematopoietic stem cell (HSC) gene therapy indicated for the treatment of early-onset metachromatic leukodystrophy (MLD)...Mobilization, CD34⁺ cell yield, drug-product characteristics and busulfan exposure were comparable to that in other patients successfully treated with arsa-cel... This case represents the first failure of engraftment of gene-corrected cells after arsa-cel administration secondary to immune response. A null ARSA genotype (absence of baseline tolerance), in the presence of active infection along with a pro-inflammatory context, sustained ARSA-specific CD4⁺ T cell responses and humoral activation support a potential multifactorial, T-cell-driven rejection of transduced cells. Individual genetic predisposition, potentially including specific HLA backgrounds, may modulate the risk of immune rejection and warrants comparative analyses with other treated patients."

Clinical • Gene therapy • CNS Disorders • Eosinophilia • Gene Therapies • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders • CD34 • CD8 • IFNG

ATIDARSAGENE AUTOTEMCEL IN METACHROMATIC LEUKODYSTROPHY: SAFETY CONSIDERATIONS FROM REAL-WORLD PRACTICE (EBMT 2026) - "Mobilised peripheral blood (G-CSF + plerixafor) was used as the CD34⁺ source in all cases, with a median collection of 37.6×10⁶ CD34⁺ cells/kg (range 19.2–62.9). All patients underwent myeloablative single-agent busulfan conditioning... The robust engraftment, sustained ARSA reconstitution and early outcomes seen in most patients in this real-world cohort of 12 patients with MLD treated with arsa-cel are consistent with those seen in the clinical development programme; however, this cohort highlights the critical importance of systematic, long-term post-therapy monitoring for the continued evaluation of the risk–benefit profile in the real world setting."

Clinical • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • Gene Therapies • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Metabolic Disorders • Rare Diseases • Thrombocytopenia • CD34

GONADAL TOXICITY AND PREMATURE OVARIAN INSUFFICIENCY AFTER HEMATOPOIETIC STEM CELL GENE-THERAPY IN FEMALE PATIENTS WITH METACHROMATIC LEUKODYSTROPHY (EBMT 2026) - "Atidarsagene autotemcel (arsa-cel) is an ex vivo autologous hematopoietic stem-cell gene therapy and it is infused intravenously following single agent busulfan conditioning. In our analysis POI is a frequent adverse effect associated with busulfan, consistent with previous reports. Sub-myeloablative exposure does not appear reducing the incidence of gonadal dysfunction compared with myeloablative regimen. Longitudinal hormonal assessments demonstrate early impairment of ovarian reserve, and the need to offer fertility preservation before arsa-cel and to initiate HRT when indicated."

Clinical • Gene therapy • Endocrine Cancer • Endocrine Disorders • Gene Therapies • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • Women's Health

A CASE OF LACK OF ENGRAFTMENT OF GENE-CORRECTED CELLS AFTER LENTIVIRAL HEMATOPOIETIC STEM CELL GENE THERAPY FOR METACHROMATIC LEUKODYSTROPHY: AN INTEGRATED CLINICAL AND IMMUNOLOGICAL INVESTIGATION (EBMT 2026) - "Background: Atidarsagene autotemcel (arsa-cel) is an autologous lentiviral haematopoietic stem cell (HSC) gene therapy indicated for the treatment of early-onset metachromatic leukodystrophy (MLD)...Mobilization, CD34⁺ cell yield, drug-product characteristics and busulfan exposure were comparable to that in other patients successfully treated with arsa-cel... This case represents the first failure of engraftment of gene-corrected cells after arsa-cel administration secondary to immune response. A null ARSA genotype (absence of baseline tolerance), in the presence of active infection along with a pro-inflammatory context, sustained ARSA-specific CD4⁺ T cell responses and humoral activation support a potential multifactorial, T-cell-driven rejection of transduced cells. Individual genetic predisposition, potentially including specific HLA backgrounds, may modulate the risk of immune rejection and warrants comparative analyses with other treated patients."

Clinical • Gene therapy • CNS Disorders • Eosinophilia • Gene Therapies • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders • CD34 • CD8 • IFNG

GALLBLADDER ABNORMALITIES IN METACHROMATIC LEUKODYSTROPHY: PRELIMINARY ANALYSIS IN PATIENTS TREATED WITH HEMATOPOIETIC STEM CELL GENE THERAPY AND UNTREATED PATIENTS (EBMT 2026) - "Atidarsagene autotemcel (arsa-cel), an autologous transplantation of CD34+ cells transduced ex vivo with a lentiviral vector encoding the ARSA gene, represents the only approved treatment for pre-symptomatic late-infantile and early-juvenile MLD, or early-symptomatic early-juvenile MLD forms... Our analysis confirms early and frequent gallbladder involvement across all MLD forms. Gallbladder wall thickening emerged as the earliest alteration and may represent the first precursor to more complex abnormalities such as polyps. The detection of ultrasound abnormalities as well as cases of cholecystectomy in patients before neurological symptom onset—including those with late-onset forms— suggests that visceral involvement may serve as an early diagnostic disease indicator."

Clinical • Gene therapy • CNS Disorders • Gene Therapies • Metabolic Disorders • CD34

LONG-TERM CLINICAL OUTCOMES OF ATIDARSAGENE AUTOTEMCEL, AUTOLOGOUS HEMATOPOIETIC STEM CELL GENE THERAPY (HSC-GT) FOR EARLY-ONSET METACHROMATIC LEUKODYSTROPHY, WITH UP TO 13 YEARS OF FOLLOW-UP (EBMT 2026) - P1/2, P2, P3 | "With up to 13 years of follow-up, arsa-cel continues to show a favourable benefit–risk profile, exhibiting a durable effect in slowing progression and preventing severe motor and cognitive impairment in most treated patients."

Clinical • Clinical data • Gene therapy • Alzheimer's Disease • Cardiovascular • Cognitive Disorders • Gene Therapies • Metabolic Disorders

A Safety and Efficacy Study of Cryopreserved OTL-200 for Treatment of Metachromatic Leukodystrophy (MLD) (clinicaltrials.gov) - P2 | N=10 | Completed | Sponsor: Orchard Therapeutics | Active, not recruiting ➔ Completed

Trial completion • Metabolic Disorders • CD14

A Safety and Efficacy Study of Cryopreserved OTL-200 for Treatment of Metachromatic Leukodystrophy (MLD) (clinicaltrials.gov) - P2 | N=10 | Active, not recruiting | Sponsor: Orchard Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

A Safety and Efficacy Study of Cryopreserved OTL-200 for Treatment of Metachromatic Leukodystrophy (MLD) (clinicaltrials.gov) - P2 | N=10 | Active, not recruiting | Sponsor: Orchard Therapeutics | Trial completion date: Apr 2028 ➔ Jan 2026

Trial completion date • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

A Safety and Efficacy Study of Cryopreserved OTL-200 for Treatment of Metachromatic Leukodystrophy (MLD) (clinicaltrials.gov) - P2 | N=10 | Recruiting | Sponsor: Orchard Therapeutics Limited | Phase classification: P3 ➔ P2

Phase classification • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

A Safety and Efficacy Study of Cryopreserved OTL-200 for Treatment of Metachromatic Leukodystrophy (MLD) (clinicaltrials.gov) - P3 | N=10 | Recruiting | Sponsor: GlaxoSmithKline

New P3 trial • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

A Safety and Efficacy Study of Cryopreserved OTL-200 for Treatment of Metachromatic Leukodystrophy (MLD) (clinicaltrials.gov) - P2 | N=10 | Active, not recruiting | Sponsor: Orchard Therapeutics | Trial completion date: Aug 2028 ➔ Apr 2028 | Trial primary completion date: Aug 2022 ➔ Apr 2022

Trial completion date • Trial primary completion date • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Newborn Screening for Metachromatic Leukodystrophy: A Combined Method of Analysis (ACMG 2026) - "A major advancement in the treatment of MLD, an FDA approved autologous, hematopoietic stem cell transplantation (Lenmeldy), has increased interest in early disease detection via newborn screening... The combined method met or exceeded the standard criteria for linearity, precision, and accuracy. Additionally, the combined method performed similarly to assays currently in use. The combined method multiplexes the evaluation of MLD with other five conditions and requires no additional DBS specimens, sample preparations, or analyses, facilitating integration into routine screening algorithms."

Bone Marrow Transplantation • Genetic Disorders • Hurler Syndrome • Metabolic Disorders • Pompe Disease • IDUA

TIGET-MLD: Gene Therapy for Metachromatic Leukodystrophy (MLD) (clinicaltrials.gov) - P1/2 | N=20 | Completed | Sponsor: Orchard Therapeutics | Active, not recruiting ➔ Completed

Trial completion • Gene Therapies • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Promises past and future - Gene therapy and the actualisation of future expectations. (PubMed, Soc Sci Med) - "The advent of gene therapies such as Zolgensma, Libmeldy, and Luxturna has given rise to new treatment options for several rare conditions, drastically changing the expectations of affected patients...Similarly marginalised issues include for instance assumptions of effectiveness that do not acknowledge the long-term uncertainty of treatment outcomes; and assumptions of profitability that run counter to real-life examples of business failure. As a revolutionary future becomes reality for some patients, such questions are becoming harder to ignore - but are crucially often omitted from discussion about projected change."

Journal • Gene Therapies