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

Treatment effect of atidarsagene autotemcel (arsa-cel) in age-matched treated vs. untreated sibling pairs with early-onset metachromatic leukodystrophy (MLD) (ASGCT 2025) - P1/2, P2 | "Given the stark difference in motor outcomes between the treated and untreated sibling pairs, this analysis reinforces the importance of early diagnosis through newborn screening to enable all early-onset patients to have the opportunity for pre-symptomatic treatment, not just the younger siblings of symptomatic patients. Disease Focus of Abstract:Storage/Lysosomal Disorders"

CNS Disorders • Gene Therapies • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • CD34

Lentiviral hematopoietic stem cell gene therapy (atidarsagene autotemcel) for late juvenile Metachromatic leukodystrophy (MLD): Interim analysis of a Phase III trial (ASGCT 2025) - P3 | "Stem cell source was mobilized peripheral blood collected after 6-8 doses of G-CSF and administration of Plerixafor 6-8 hours before leukapheresis...All patients received myeloablative conditioning with busulfan as a single agent, with a cumulative target area under the curve of 85 mg×h/L...Conclusion This interim analysis suggests that the drug product characteristics, short-term safety profile, and pharmacodynamic efficacy of arsa-cel in LJ-MLD align with previous studies in early-onset MLD. Further follow-up is ongoing to assess brain imaging, clinical efficacy endpoints, and long-term safety Disease Focus of Abstract:Inherited Neurological Disorders"

Gene therapy • P3 data • P3 data: top line • CNS Disorders • Gene Therapies • Lysosomal Storage Diseases • Metabolic Disorders • Oncology • Rare Diseases • CD34

Encapsulated cell therapy demonstrated therapeutic efficacy in metachromatic leukodystrophy and sustained ARSA production in NHP (ASGCT 2025) - "Libmeld"

Clinical • CNS Disorders • Gene Therapies • Inflammation • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Effects of atidarsagene autotemcel gene therapy on peripheral nerves in late-infantile metachromatic leukodystrophy. (PubMed, Brain) - "In addition to the potential role of early age at treatment in the preservation of myelin, supraphysiological ARSA levels may slow demyelination of the DPN and other peripheral nerves. Arsa-cel may exert a stronger effect on NCV than allogeneic hematopoietic stem cell transplantation due to its greater ARSA expression."

Journal • Bone Marrow Transplantation • Gene Therapies • Metabolic Disorders • Pain • Transplantation

Treatment of leukodystrophies: Advances and challenges. (PubMed, Eur J Paediatr Neurol) - "Gene therapy has become a viable option, with ex vivo approaches like atidarsagene autotemcel providing promising outcomes for early-onset MLD...Despite these advances, challenges remain, including the ultrarare nature of most leukodystrophies, limited natural history data, high treatment costs, and barriers to accessibility. Future developments, including newborn screening and close international collaboration, aim to enhance early diagnosis, refine treatment timing, and expand access to innovative therapies."

Journal • Review • Bone Marrow Transplantation • CNS Disorders • Gene Therapies • Genetic Disorders • Metabolic Disorders • Rare Diseases • Transplantation

Long-Term Effects of Atidarsagene Autotemcel for Metachromatic Leukodystrophy. (PubMed, N Engl J Med) - P1/2, P2 | "Among patients with presymptomatic late-infantile or early-juvenile MLD and those with early-symptomatic early-juvenile MLD, the risk of severe motor impairment or death was significantly lower among those who received treatment with arsa-cel than in a natural history cohort that did not receive treatment. (Funded by Orchard Therapeutics and others; ClinicalTrials.gov numbers, NCT01560182 and NCT03392987.)."

Journal • Febrile Neutropenia • Gene Therapies • Hematological Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Neutropenia • Oncology • Rare Diseases

TREATMENT EFFECT OF ATIDARSAGENE AUTOTEMCEL (ARSA-CEL) IN AGE-MATCHED TREATED VS. UNTREATED SIBLING PAIRS WITH EARLY-ONSET METACHROMATIC LEUKODYSTROPHY (MLD) (EBMT 2025) - P1/2, P2 | "The results for the subset of sibling pairs align with the previously presented data from the presymptomatic LI and EJ CDP population vs. the NHx cohort. Given the stark difference in motor outcomes between the treated and untreated sibling pairs, this analysis reinforces the importance of early diagnosis through newborn screening to enable all early-onset patients to have the opportunity for pre-symptomatic treatment, not just the younger siblings of symptomatic patients."

CNS Disorders • Gene Therapies • Genetic Disorders • Metabolic Disorders

TREATMENT EFFECT OF ATIDARSAGENE AUTOTEMCEL (ARSA-CEL) IN AGE-MATCHED TREATED VS. UNTREATED SIBLING PAIRS WITH EARLY-ONSET METACHROMATIC LEUKODYSTROPHY (MLD) (EBMT 2025) - P1/2, P2 | "The results for the subset of sibling pairs align with the previously presented data from the presymptomatic LI and EJ CDP population vs. the NHx cohort. Given the stark difference in motor outcomes between the treated and untreated sibling pairs, this analysis reinforces the importance of early diagnosis through newborn screening to enable all early-onset patients to have the opportunity for pre-symptomatic treatment, not just the younger siblings of symptomatic patients."

CNS Disorders • Gene Therapies • Genetic Disorders • Metabolic Disorders

Diversity, Equity, and Inclusion in Gene and Cell Therapies Clinical Trials (ISPOR 2025) - "The lowest enrollment was for atidarsagene autotemcel (7 participants), while sipuleucel-T had the highest (512 participants)...White participants were disproportionately represented, particularly in sipuleucel-T (90.0%) and talimogene laherparepvec (97.9%). The findings revealed persistent racial disparities in gene and cell therapy clinical trials, with minority populations underrepresented and White participants comprising the majority. Achieving DEI in clinical trials remains a challenge, underscoring the need for greater efforts to address these disparities."

Clinical • Gene Therapies • Oncology

Orchard Therapeutics Announces Reimbursement Agreement in Spain (PRNewswire) - "Orchard Therapeutics...announced it has recently reached an agreement with the Interministerial Commission for the Pricing of Medicines of the Directorate of Common Portfolio of Services of the Spanish National Health System (SNS) which will result in reimbursed access to Libmeldy (atidarsagene autotemcel) for all eligible children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ) or early symptomatic early juvenile (ESEJ)—collectively referred to as early-onset—metachromatic leukodystrophy (MLD)."

Reimbursement • Metabolic Disorders

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

FDA Comments - Lenmeldy (TCT-ASTCT-CIBMTR 2025) - No abstract available

Lenmeldy (TCT-ASTCT-CIBMTR 2025) - No abstract available

Finding a Way for Patients to Access Gene Therapies (ISPOR-EU 2024) - "Out of 9 funded single-administration GTx (eladocagene exuparvovec, etranacogene dezaparvovec, betibeglogene autotemcel, valoctocogene roxaparvovec, voretigene neparvovec, exagamglogene autotemcel, lovotibeglogene autotemcel, atidarsagene autotemcel, onasemnogene abeparvovec), RSAs were identified in the US (n=7), UK (n=5), Canada (n=3), and Australia (n=2)... To manage uncertainties around long-term benefits and financial impact, local decision-makers implement RSAs. Canada and UK mainly use financial-based schemes built on simple price discounts. Australia and the US aim at implementing schemes whereby treatment cost payers incur corresponds to expected health outcome for a particular patient."

Clinical • Gene therapy • Gene Therapies • Rare Diseases

Health Technology Appraisals of Gene Therapies Appraised Through NICE Highly Specialized Technology Route (ISPOR-EU 2024) - " To date (May 2024), NICE has appraised eight gene therapies through the HST route; five single-dose therapies (Strimvelis; Luxturna; Zolgensma; Libmeldy; Upstaza), and three enzyme replacement therapies with long-term dosages (Strensiq; Lamzede; Kanuma)... This overview of prior NICE HST appraisals of gene therapies provides insight to the potential issues faced by all stakeholders involved in technology appraisals of these innovative treatments. It also demonstrates the array of products that “gene therapies” captures, the differences in acquisition prices, and variation in economic model structure and approach."

Gene therapy • Gene Therapies • Rare Diseases

Exploring Long-Term Durability Assumptions in Cost-Effectiveness Models of Cell and Gene Therapies: A Study of 39 Health Technology Assessments (ISPOR-EU 2024) - "All HTA bodies reviewed onasemnogene abeparvovec whereas exagamglogene autotemcel was only assessed by ICER...The assumed treatment durability across HTAs was widest for atidarsagene autotemcel (12 years to lifetime; n=3) and narrowest for voretigene neparvovec (10 to 40 years; n=4)... There are notable variations in the long-term durability assumptions of rare disease CGTs in HTAs. Modeling methods are evolving and building on past precedents. Further analysis is needed to unearth the most influential factors affecting durability assumptions."

Cost effectiveness • Gene therapy • HEOR • Gene Therapies • Genetic Disorders • Rare Diseases

Drivers of Access to Gene Therapies in Poland and Selected Central and Eastern Europe Countries (ISPOR-EU 2024) - " The review identified 11 HTA reports on 6 single-administration GTx (eladocagene exuparvovec, etranacogene dezaparvovec, valoctocogene roxaparvovec, voretigene neparvovec, atidarsagene autotemcel, onasemnogene abeparvovec)... The availability of GTx in selected CEE countries is limited. Considering there are 88 ongoing GTx phase 3 clinical trials, with 58 expected to be completed within the next 5 years, the decision-makers will likely face even greater challenges to balance patient access and impact on public budgets."

Gene therapy • Gene Therapies • Rare Diseases

'Lenmeldy (OTL-200) in MLD: FDA's validation of advanced therapy'. (PubMed, Ann Med Surg (Lond)) - No abstract available

Journal • Metastases

Unlocking Equitable Access to Revolutionary Cell and Gene Therapies Across EU Member States (ISPOR-EU 2024) - "Access to C>s is highly variable, especially across mid-sized cost-effectiveness countries. This is likely due to smaller target populations and the high price of C>s reducing affordability and pushing the incremental cost-effectiveness ratios above accepted thresholds. Although economic discussions have been shown to be a tool for resource rationalization and efficiency, their impact on equity may need to be re-considered."

Gene therapy • Gene Therapies

The Cost-Effectiveness of Atidarsagene Autotemcel (arsa-cel) for the Treatment of Metachromatic Leukodystrophy (MLD) in Spain (ISPOR-EU 2024) - "Arsa-cel has shown to be cost-effective for the Spanish NHS versus BSC."

Cost effectiveness • HEOR • CNS Disorders • Gene Therapies • Metabolic Disorders

Managed Entry Agreements for Advanced Therapy Medicinal Products: Insights From Semi-Structured Interviews Across England, the Netherlands, and Spain (ISPOR-EU 2024) - "Recently, an OBA for Atidarsagene autotemcel was proposed but not implemented... The current ATMP oncological pipelines pose additional threats to limited budgets. The dissemination of experiences in negotiating and reimbursing ATMPs is crucial as it provides valuable insights for shaping future practices and exploiting learnings gained elsewhere."

Interview • Metastases

From Pipeline to Pricing & Reimbursement: Economic Impact and Access Challenges of Upcoming Gene Therapies (ISPOR-EU 2024) - "Rare indications still dominate the pipeline, with an ever increasing price- Lenmeldy recently launched at $4.25m in the US- posing ongoing affordability and access challenges. However, the emergence of gene therapies targeting indications with larger prevalences, such as diabetes and Parkinson’s disease, alongside technological advancements (e.g. gene editing and re-dosing) may shift the gene therapy reimbursement and pricing expectations in the future."

Gene therapy • HEOR • Pricing • Reimbursement • US reimbursement • CNS Disorders • Diabetes • Gene Therapies • Metabolic Disorders • Movement Disorders • Parkinson's Disease

Recent Developments in European Voluntary Cross-Border Collaborations in Joint HTA, Drug Pricing, Procurement, and Readiness for EU HTA Implementation (ISPOR-EU 2024) - "BeNeLuxA successfully completed joint price negotiations for atidarsagene autotemcel in 2024 and is currently conducting joint HTA of another high-price gene therapy... Established cross-border cooperations like JNHB and BeNeLuxA are poised to maintain their work post-EU HTA regulation implementation. Given the tight timelines and anticipated challenges for national implementation of EU HTA, these collaborations are expected to streamline and accelerate local processes through PICO alignment and/or integration of joint clinical assessment reports for national decision-making. Furthermore, the growing interest in voluntary cooperation on HTA within EU and European Commission’s ambitions to reinforce cross-country collaborations supporting pricing and reimbursement policies underscore the evolving landscape of cross-border collaborations."

Pricing • Gene Therapies

Cost-Effectiveness of Atidarsagene Autotemcel (ARSA-CEL) Gene Therapy for Treating Metachromatic Leukodystrophy (MLD) in Ireland, Belgium, and the Netherlands As a Part of the Beneluxa Initiative (ISPOR-EU 2024) - "Findings suggest arsa-cel yields lifelong QoL improvements, with variable cost-effectiveness among countries due to differing modelling requirements and inputs. Scenario analyses reveal that including broader considerations, such as the societal perspective, newborn screening, and impact on caregivers, considerably lowers all the ICERs, underscoring arsa-cel's value."

Cost effectiveness • Gene therapy • HEOR • Gene Therapies • Metabolic Disorders

Atidarsagene autotemcel (autologous hematopoietic stem cell gene therapy) preserves cognition, language, and speech and slows brain demyelination and atrophy in early-onset metachromatic leukodystrophy (ESGCT 2024) - No abstract available

Gene therapy • Gene Therapies • Metabolic Disorders