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

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

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

Willingness to Pay for Ultra-Rare Diseases in US, Germany, France, UK, and Japan: A Comparative Study (ISPOR-EU 2024) - "Elevidys (DMD) with a WAC price of $3.2 million in US and Upstaza (AADC deficiency) with a list price of €3.5million in France are amongst the highest priced treatments globally... WIP for treatments for ultra rare diseases specifically gene therapies is very high and HTA institutions and payers have recognised the value of curative treatments reflected through positive HTA and price outcomes."

Gene Therapies • Genetic Disorders • Pediatrics • 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

PTC Therapeutics Enters into Agreement to Sell Priority Review Voucher for $150 Million (PTC Therapeutics) - "PTC Therapeutics, Inc...announced...that it has entered into an agreement to sell its Rare Pediatric Disease Priority Review Voucher (PRV) for $150 million upon the closing of the transaction...PTC was granted the PRV on November 13, 2024 along with the U.S. Food and Drug Administration (FDA) approval of KEBILIDI (eladocagene exuparvovec-tneq) for the treatment of children and adults with AADC deficiency, including the full spectrum of disease severity...The transaction is subject to customary closing conditions, including expiration of the applicable waiting period under the Hart-Scott Rodino (HSR) Antitrust Improvements Act."

Commercial • Genetic Disorders

Evaluating Key Drivers for Patient Access and Pricing Trends in ATMPs Across Germany, France, and the UK (ISPOR-EU 2024) - "The analysis highlights the significant variability in HTA outcomes and pricing for ATMPs across Germany, France, and the UK. These findings emphasize the importance of trial design, including factors like open-label status or the use of a natural history comparator arm, in influencing payers’ willingness to pay. Understanding these key drivers is crucial for assessing the robustness of trial evidence required to achieve a certain level of added clinical benefit."

Clinical • Pricing

Cost-Effectiveness Analysis of Eladocagene Exuparvovec for the Treatment of Aromatic L-Amino Acid Decarboxylase Deficiency (AADCd) From a United States (US) Perspective (ISPOR-EU 2024) - "This study suggests that patients have significant LY and QALY gains with EE treatment compared to BSC, indicating that EE is a transformative treatment for AADCd. Strengths included alternative approaches to model motor function, with consistent findings across models. Moreover, use of the Total PDMS-2 score MSD provides a more responsive measure of motor-function improvements in AADCd than MM achievement alone."

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

Optimizing the anesthetic care of patients with aromatic l-amino acid decarboxylase deficiency. (PubMed, Paediatr Anaesth) - "Postoperative intensive care management is necessary for consideration of postoperative extubation and provision of supportive care. With careful planning, preparation, and vigilance, patients with AADC deficiency can safely undergo anesthesia."

Journal • Review • Anesthesia • Critical care • Developmental Disorders • Gene Therapies • Genetic Disorders • Hypoglycemia

Unlocking potential: Long-term motor, language and cognitive advancement following Upstaza gene therapy (SSIEM 2024) - "Sponsored by PTC THERAPEUTICS"

Gene therapy • Gene Therapies

ELADOCAGENE EXUPARVOVEC GENE THERAPY IMPROVES MOTOR DEVELOPMENT IN PATIENTS WITH AROMATIC L-AMINO ACID DECARBOXYLASE DEFICIENCY (SSIEM 2024) - "Eladocagene exuparvovec had a durable, positive impact on motor development, in patients with AADCd with an acceptable safety profile."

Clinical • Gene therapy • CNS Disorders • Gene Therapies • Genetic Disorders • Insomnia • Movement Disorders • Sleep Disorder

AN OPEN-LABEL STUDY OF ELADOCAGENE EXUPARVOVEC ADMINISTERED USING THE SMARTFLOW MAGNETIC RESONANCE-COMPATIBLE VENTRICULAR CANNULA IN PAEDIATRIC PARTICIPANTS: 48-WEEK INTERIM ANALYSIS (SSIEM 2024) - "Significantly increased CSF HVA levels and F-DOPA uptake from baseline were sustained up to 48 weeks following treatment with eladocagene exuparvovec in participants with AADC deficiency and coincided with the increased acquisition of motor milestones."

Clinical • Developmental Disorders • Gene Therapies • Genetic Disorders • Movement Disorders • Pediatrics

Unlocking the potential of patients with AADC deficiency (SSIEM 2024) - "Sponsored by PTC THERAPEUTICS This symposium will review long-term data from the clinical study of Upstaza (eladocagene exuparvovec) gene therapy for the treatment of AADC deficiency, with real-world outcomes explored through patient case studies. There will be an introductory overview of AADC deficiency and Upstaza, as well as a focus on rehabilitation strategies to optimise post- treatment outcomes."

Clinical • Gene Therapies • Genetic Disorders

Immune responses to central nervous system directed adeno-associated virus gene therapy: Does direct CNS delivery make a difference? (PubMed, Neurotherapeutics) - "Despite these contrasting parallels, these therapeutics and others in the clinic have demonstrated clinical benefit for patients, warranting further exploration of immune responses to CNS-directed AAV clinical trials. Thus, in this review, we discuss effects of different routes of AAV administration on eliciting local and peripheral immune responses specifically observed in CNS-targeted trials."

Gene therapy • Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • Gene Therapies • Genetic Disorders • Metabolic Disorders • Movement Disorders • Pain • Parkinson's Disease • Rare Diseases

PTC Therapeutics Announces FDA Acceptance and Priority Review of the BLA for Upstaza (PRNewswire) - "PTC Therapeutics, Inc...announced today that the FDA has accepted for filing the Biologics License Application (BLA) for Upstaza (eladocagene exuparvovec), a gene therapy for the treatment of AADC deficiency. The application has been granted Priority Review with a target regulatory action date of November 13, 2024."

BLA • PDUFA • Priority review • Genetic Disorders • Metabolic Disorders

Immunomonitoring requirements in AAV based gene therapy clinical trials: where do we stand? (ESGCT 2023) - "Promising results have been obtained with several rAAV products as illustrated by six drugs currently approved (Luxturna, Zolgensma, Roctavian, Hemgenix, Upstaza and Elevidys) in Europe and USA...Finally, we will describe the general work-flow to implement clinical immune monitoring, in line with Good Clinical Laboratory Practices (GCLP) and other regulatory guidelines. Beyond the method validation itself, other steps, such as definition of responsibilities, personnel training or data and material traceability have to be implemented and controlled by the immunology laboratory to assess safety and efficacy endpoints, while ensuring the quality and integrity of the data."

Clinical • Gene therapy • Gene Therapies

Our initial experience with intraputaminal delivery of Upstaza using MRI‐guidance for cannula placement and confirmation of infusion target coverage (ESGCT 2023) - "Overall, this study demonstrates the safety and feasibility of direct, intraparenchymal gene therapy infusion to the brain. Furthermore, MRI-guidance can be used to confirm accurate placement of the cannula and also provide intra-procedural visualization of the infusion which can be extremely important considering the potential for reflux and perivascular off-target spread."

CNS Disorders • Dystonia • Gene Therapies • Genetic Disorders • Movement Disorders • Pediatrics

AAV KP1 Efficiently Transduces Human Cell Lines In Vitro and Mouse Liver but Not Non-Human Primate Liver After Intravenous Injection (ASGCT 2024) - "To date, seven AAV gene therapy drugs have been approved including Glybera (2012), Luxturna (2017), Zolgensma (2019), Upstaza (2022), Roctavian (2022), Hemgenix (2022), and ELEVIDYS (2023)...Our observation is consistent with other reported studies in rhesus and cynomolgus monkeys (Pekrun et al., 2022; Catalyst Biosciences, 2020). The underlying cause of low transduction in NHP liver remains to be understood and whether KP1 can efficiently transduce human hepatocytes in human patients remains unknown."

Preclinical • Gastrointestinal Cancer • Gene Therapies • Hepatocellular Cancer • Liver Cancer • Solid Tumor

Cell and Gene Therapy Access in the US and European Countries (ISPOR 2024) - " Market access status of available cell/gene therapies varied considerably among these markets: US: 27 FDA-approved therapies (8 are cord blood products), 18 of which are marketed and reimbursed Europe: 17 EC-authorized therapies currently available US and Europe: 9 therapies are available across both jurisdictions Cell and gene therapy with highest annual visible ex-factory vary: US was Hemgenix (etranacogene dezaparvovec-drlb) at $3.5M; Europe was Upstaza (eladocagene exuparvove) at $3.8M (Germany) European net therapy cost following negotiation include ~10% to 45% reductions from the visible ex-factory price with some as high as ~60% (e.g. Roctavian- valoctocogene roxaparvovec, in Germany)... Cell and gene therapy space is growing with several products now on the market. Visible ex-factory prices continue to set new records raising concerns about affordability and sustainability, while the gulf between ex-factory and net prices seems to be increasing. Growing..."

Gene therapy • Gene Therapies

Pharmacodynamics of Eladocagene Exuparvovec and Safety of the SmartFlow Magnetic Resonance-compatible Ventricular Cannula for Administering Eladocagene Exuparvovec in Pediatric Participants (AAN 2024) - "CSF HVA levels and F-DOPA uptake increased significantly 8 weeks post-eladocagene exuparvovec gene therapy in pediatric participants with AADC deficiency, indicating dopamine production. No treatment-emergent AEs were deemed related to the SmartFlow MR-compatible surgical device used for gene therapy delivery."

Clinical • PK/PD data • Anemia • Developmental Disorders • Gene Therapies • Genetic Disorders • Hematological Disorders • Hypotension • Movement Disorders • Pediatrics • Renal Disease