Kebilidi (eladocagene exuparvovec-tneq) / PTC Therapeutics - LARVOL DELTA

A Single-Stage, Adaptive, Open-label, Dose Escalation Safety and Efficacy Study of AADC Deficiency in Pediatric Patients (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Krzysztof Bankiewicz | Trial completion date: Mar 2037 ➔ Aug 2037 | Trial primary completion date: Mar 2029 ➔ Aug 2027

Trial completion date • Trial primary completion date • Genetic Disorders • Pediatrics

Gene therapy in an adult patient with AADC deficiency (SSIEM 2026) - "a) AADC deficiency can lead to neurological deterioration in adulthood due to the progressive reduction in residual biogenic amine synthesis in the brain. b) This severe case of AADC deficiency indicates that adult patients tolerate intraputaminal Upstaza treatment well and can experience positive clinical responses."

ADC • Clinical • Gene therapy • CNS Disorders • Developmental Disorders • Dystonia • Gastrointestinal Disorder • Gene Therapies • Genetic Disorders • Metabolic Disorders • Movement Disorders

Trends in the Engineering of Adeno-Associated Virus (AAV) for Precision Gene Delivery to the Central Nervous System (CNS). (PubMed, Int J Mol Sci) - "Despite these challenges, our understanding of AAV structure and technological advances continue to enable researchers to develop innovative strategies that have resulted in groundbreaking, FDA-approved therapeutic products now available for Leber congenital amaurosis (LCA) (Luxturna®), spinal muscular atrophy (SMA) (Zolgensma®), and the two recent gene therapy products for aromatic L-amino acid decarboxylase (AADC) deficiency, Kebilidi® and Upstaza®, which currently hold FDA and EMA approval, respectively. This review aims to highlight recent advances in the field of AAV gene therapy for neurological disorders, identify research gaps, and suggest areas for future investigation to enable potential breakthroughs particularly in neurodegenerative, neurodevelopmental, and neuromuscular disorders. We foresee that more tissue- and cell-specific AAV vectors designed using AI-powered platforms will emerge to precisely and efficiently target specific brain..."

Journal • Review • Alzheimer's Disease • CNS Disorders • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Movement Disorders • Muscular Atrophy • Parkinson's Disease • Rare Diseases

A Single-Stage, Adaptive, Open-label, Dose Escalation Safety and Efficacy Study of AADC Deficiency in Pediatric Patients (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Krzysztof Bankiewicz | Trial completion date: Jul 2031 ➔ Mar 2037 | Trial primary completion date: Jul 2027 ➔ Mar 2029

Trial completion date • Trial primary completion date • Genetic Disorders • Pediatrics

Gene Therapy for Amino Acid Decarboxylase Deficiency: Clinical and Imaging Outcomes in a French Cohort. (PubMed, Mov Disord) - "Eladocagene exuparvovec offers durable clinical benefits across diverse genotypes. Therapeutic efficacy and the subsequent neuroplasticity sequence seem to depend on reaching a critical threshold of dopamine production rather than on exhaustive anatomical coverage of the putamen."

Journal • CNS Disorders • Gene Therapies • Genetic Disorders • Movement Disorders • Parkinson's Disease

What is the formula for commercial success of a gene therapy? Reflections on approved GTx (ASGCT 2026) - "Indication selection: Commercial success across Casgevy®, Vyjuvek®, Elevidys® and Zolgensma® reinforce five criteria that appear pivotal for gene therapy success...Beqvez® (hemophilia B) appears to have treated no patients between FDA approval (2024) and market withdrawal (2025), while Hemgenix® treated 12 patients in its first year (<0.1% penetration). Uptake has also remained minimal for Zevaskyn® and Zynteglo® (beta-thalassemia).By contrast, Elevidys® (DMD) treated approximately 900 patients in the US within two years of FDA approval, although it did not receive EU authorization... The number of clinical study initiations increased continuously over the observation period, rising by 430% from 27 ongoing company sponsored programs in 2016 to 143 in 2025. After steady growth until 2021, development activity accelerated markedly from 2022 onward, with the pipeline almost doubling between 2022 and 2023. After a peak in 2024,..."

Gene therapy • Beta-Thalassemia • CNS Disorders • Duchenne Muscular Dystrophy • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Hepatology • Liver Failure • Metabolic Disorders • Movement Disorders • Muscular Atrophy • Muscular Dystrophy • Ophthalmology • Rare Diseases

Rational for dose selection for intracerebroventricular AAV9 gene therapy using a CTNNB1 gene therapy model (ASGCT 2026) - P1/2 | "These include AAV9- based therapies for spinal muscular atrophy (SMA), administered intravenously (Zolgensma™) or intrathecally (Itvisma™); an intravenously delivered AAV-based therapy for Duchenne muscular dystrophy (Elevidys™); and AAV2-based therapies delivered subretinally to the eye (Luxturna™) or directly to the brain parenchyma (e.g. intraputaminal administration of Upstaza™)...Prioritizing CNS mRNA expression as an efficacy reference point, while achieving exposures at least two-fold below the NOAEL with supportive safety data, enables ethically justified first-in-human dosing decisions in AAV-based CNS gene therapy trials. This framework is intended to inform dose selection strategies across emerging CNS gene therapy programs beyond a single indication."

First-in-human • Gene therapy • CNS Disorders • Developmental Disorders • Duchenne Muscular Dystrophy • Gene Therapies • Movement Disorders • Muscular Atrophy • Muscular Dystrophy • Rare Diseases • CTNNB1

Neuronal transduction mechanism analysis of AAV2-derived CereAAV.YN vector (ASGCT 2026) - "Results Under both AAV2- and CereAAV.YN-infected conditions, we identified several genes previously reported as key host factors for AAV2 entry and trafficking, including AAVR, VPS29, and VPS35, confirming the robustness of the screening strategy.Notably, multiple genes were selectively enriched only in the CereAAV.YN-infected condition but not in the AAV2 condition, suggesting the presence of CereAAV.YN-specific host factors that may mediate its enhanced BBB penetration. Conclusion We are currently validating these candidate genes to determine their functional contribution to CereAAV.YN-mediated gene delivery to the CNS."

CNS Disorders • Gene Therapies • Genetic Disorders

Review of Viral Shedding Profiles in Approved AAV-Based Gene Therapy Products: Implications for Safety and Environmental Impact (ASGCT 2026) - "The GTPs were categorized based on their route of administration: locally administered (Luxturna, Upstaza, Glybera, Adstiladrin) and systemically administered (Beqvez, Roctavian, Hemgenix, Elevidys, Zolgensma)...Given that AAV is non-pathogenic to humans, it is feasible to standardize and simplify viral shedding monitoring in clinical studies. The standardization could streamline sampling schedules, reducing the burden on patients while still generating sufficient data to address potential transmission and environmental risks in compliance with regulatory requirements."

Clinical • Gene therapy • Review • Duchenne Muscular Dystrophy • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Movement Disorders • Muscular Atrophy • Muscular Dystrophy • Rare Diseases

Preclinical gene therapy for tyrosine hydroxylase deficiency (ASGCT 2026) - "A midbrain- targeted stereotactic approach in adult THD mice showed significant improvements in motor and neurocognitive phenotypes, dopamine neurotransmitter levels, and was well-tolerated at study endpoint of 6 months. Our study is the first AAV gene therapy efficacy study for THD, showing comprehensive preclinical efficacy and safety datasets towards translation."

Gene therapy • Preclinical • Alzheimer's Disease • Cerebral Palsy • CNS Disorders • Cognitive Disorders • Gene Therapies

852152: Gene Therapy in Action: Real-World Implementation in Clinical Genetics (ACMG 2026) - "Rebecca Ahrens-Nicklas on safety monitoring. Join us as we address the practical realities behind gene therapy delivery and discuss how to prepare the workforce and infrastructure for this rapidly advancing field.Learning Objectives:• Describe the current landscape, clinical indications, and post-marketing safety considerations of FDA-approved gene therapies.• Identify pharmacy requirements for the safe handling, preparation, and administration of gene therapy products.• Outline the clinicians role in coordinating multidisciplinary gene therapy care, including approval processes, administration, follow-up, and adverse event reporting."

Clinical • Gene therapy • Real-world • Real-world evidence • Gene Therapies • Genetic Disorders

Potential impact of early pharmacological treatment on gene therapy outcomes in AADC deficiency. (PubMed, Parkinsonism Relat Disord) - No abstract available

Journal • CNS Disorders • Gene Therapies • Genetic Disorders • Movement Disorders • Parkinson's Disease

Pharmacodynamics, Efficacy, and Safety of Intraputaminal Eladocagene Exuparvovec Administered to Pediatric Patients With Aromatic L-Amino Acid Decarboxylase Deficiency Using an MR-Compatible Cannula: 48 Weeks of Follow-Up. (PubMed, J Inherit Metab Dis) - P2 | "This study provides further evidence of the favorable pharmacodynamic, efficacy, and safety profile of eladocagene exuparvovec in children with AADC deficiency; intraputaminal administration using an MR-compatible cannula was well tolerated. Study GT-002 (NCT04903288) provides further evidence of the favourable pharmacodynamic, efficacy and safety profile of eladocagene exuparvovec gene therapy in children with AADC deficiency over 48 weeks and demonstrates that intraputaminal administration using an MR-compatible cannula was well tolerated, allowing for real-time MRI confirmation of cannula placement and infusate coverage, and for accurate dosing to the putamen."

Journal • PK/PD data • Developmental Disorders • Gene Therapies • Genetic Disorders • Pediatrics

Frameless intraputaminal delivery of gene therapy with eladocagene exuparvovec in patients with aromatic L-amino acid decarboxylase deficiency: safe and efficient results. (PubMed, Childs Nerv Syst) - "Frameless, neuronavigated gene therapy for AADC deficiency proved both feasible and safe, with early clinical improvements observed in motor function and symptom control. This technique offers a promising alternative to frame-based methods and expands treatment options for this rare neurometabolic disorder."

Journal • Gene Therapies • Genetic Disorders • Metabolic Disorders • Pediatrics

Evaluating the Impact of Different Payment Models on the Cost-Effectiveness and Budget Impact of Cell and Gene Therapies: Eladocagene Exuparvovec As a Case Study (ISPOR-EU 2025) - "In this case, the outcome-based instalment payment model seemed most favourable for financial sustainability and payer value. By combining upfront risk-sharing with payments tied to patient outcomes, it balances short-term affordability with long-term value, reducing budgets and improving ICER, which was still above commonly used thresholds."

Case study • Clinical • Cost effectiveness • Gene therapy • HEOR • Gene Therapies • Genetic Disorders

Eladocagene Exuparvovec for the Treatment of Aromatic L-Amino Acid Decarboxylase Deficiency (AADCd): An Economic Evaluation from a US Perspective. (PubMed, Pharmacoeconomics) - "Eladocagene exuparvovec is associated with considerable QALY gains compared with BSC. Within the context of other ultra-rare and/or one-time treatments, eladocagene exuparvovec provides substantial clinical improvements at lower cost than many other rare-disease treatments. Findings from this study highlight that eladocagene exuparvovec is an important treatment option for patients with AADCd."

HEOR • Journal • Developmental Disorders • Gene Therapies • Genetic Disorders • Rare Diseases

Understanding and characterizing the immune response to adeno-associated virus (AAV) in the central nervous system (CNS) (ASGCT 2025) - "Future work will include testing the role of Tregs in transgene expression through Treg depletion and further elucidating the mechanism of T cell recruitment to the brain for the creation of safer and more effective AAV gene therapies. Disease Focus of Abstract:Central Nervous System Disorders"

Gene Therapies • Hepatology • Liver Failure • CD4 • CXCL10 • FOXP3 • IFNG • IL2RA • ISG20

Structural Characterization of Antibody Interactions from Infants with AAV2-associated Hepatitis to Guide Rational Capsid Redesign (ASGCT 2025) - "Furthermore, regions occluded by the Fab provide insights into the mechanism by which these NAbs inhibit transduction. Disease Focus of Abstract:None"

CNS Disorders • Depression • Gene Therapies • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Pediatrics • Psychiatry

2025 Review of Gene Therapy Access Landscape (ISPOR 2025) - "For gene therapies, the proportion of covered lives facing non-coverage has increased. Ultra-high-cost therapies continue to face additional restrictions compared to lower-priced gene therapies. Therapies on market longer face less restrictive management, likely due to contracting strategies."

Gene therapy • Review • Gene Therapies

Cost-Effectiveness Analysis of Eladocagene Exuparvovec-tneq for Aromatic L-Amino Acid Decarboxylase Deficiency (AADC-D) and Comparison with Other Rare Disease One-Time Treatments in the United States (ISPOR 2025) - "Eladocagene exuparvovec-tneq has substantial QALY gains compared to BSC and demonstrates superior cost-effectiveness relative to other rare-disease and one-time treatments. These findings highlight the transformative impact of this gene therapy for treating AADCd."

Cost effectiveness • HEOR • Developmental Disorders • Gene Therapies • Genetic Disorders • Metabolic Disorders • Rare Diseases

Eladocagene Exuparvovec for Aromatic L-Amino Acid Decarboxylase Deficiency. (PubMed, JAMA) - No abstract available

Journal • Genetic Disorders

Clinically meaningful improvements after gene therapy for aromatic L-amino acid decarboxylase deficiency (AADCd) in the Peabody Developmental Motor Scale, Second Edition (PDMS-2) and correlation with Bayley-III scores and motor milestones. (PubMed, Orphanet J Rare Dis) - "The MSD of 40 points for Total PDMS-2 score enables the interpretation of changes observed in patients with AADCd, and suggests that treatment with eladocagene exuparvovec leads to significant improvements in motor and cognitive function."

Journal • Developmental Disorders • Gene Therapies • Genetic Disorders • Movement Disorders

Estimating health state utilities for aromatic L-amino acid decarboxylase deficiency (AADCd) in the United States. (PubMed, Health Qual Life Outcomes) - "This study implemented TTO methods to estimate utilities for five health states which reflect the burden and impact of AADCd. The range in values from the most to least severe health state suggests that there is potential for effective treatments to substantially improve quality of life in these patients."

Journal • Genetic Disorders • Metabolic Disorders

Orsini the Exclusive Specialty Pharmacy Provider for Gene Therapy KEBILIDI (eladocagene exuparvovec-tneq) (PRNewswire) - "Orsini announced today that it has been chosen by PTC Therapeutics as the exclusive specialty pharmacy provider for the adeno-associated virus vector-based gene therapy KEBILIDI (eladocagene exuparvovec-tneq). KEBILIDI is approved by the U.S. Food and Drug Administration for the treatment of adult and pediatric patients with aromatic L-amino acid decarboxylase (AADC) deficiency and is the seventh treatment to join Orsini's cell and gene therapy portfolio."

Commercial • Genetic Disorders

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