Roctavian (valoctocogene roxaparvovec-rvox) / BioMarin - LARVOL DELTA

Impact of Gene Therapy on the Haemophilia-Free Mind: Outcomes Before and After Valoctocogene Roxaparvovec in GENEr8-1 Trial Participants. (PubMed, Haemophilia) - P3 | "This expert-led analysis demonstrates application of the haemophilia-free mind framework to clinical trial data using existing outcome measures. Mapping GENEr8-1 data to this framework demonstrated improvements of up to 33% in domains that contribute towards a haemophilia-free mind in participants after valoctocogene roxaparvovec treatment."

Journal • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

MTE #24: Gene Therapies and Hepatotoxicity (Ticketed) (AASLD 2026) - "Multiple gene therapies have been approved in recent years by the US Food and Drug Administration (FDA) for a variety of inherited disorders, including: Duchenne muscular dystrophy (delandistrogene moxeparvovec-rokl, 2023) Hemophilia A (valoctocogene roxaparvovec-rvox, 2023) Hemophilia B (etranacogene dezaparvovec-drlb, 2022; fidanacogene elaparvovec-dzkt, 2024) Spinal muscular atrophy (onasemnogene abeparvovec-brve, 2025) Sickle cell disease (exagamglogene autotemcel, 2023)...Identify clinically available AAV gene therapy treatments. Discuss ways to identify and potentially mitigate hepatotoxicity, and to optimize care for patients and study participants receiving AAV gene therapy."

Gene therapy • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Hepatology • Liver Failure • Movement Disorders • Muscular Atrophy • Muscular Dystrophy • Rare Diseases • Sickle Cell Disease

Bridging the Gap: A Systematic Review of Modern Hemophilia Therapies and Global Inequities in Clinical Trial Participation. (PubMed, Haemophilia) - "Modern therapies demonstrate strong efficacy and acceptable safety, with several approved agents. However, persistent global inequities in trial participation and access highlight the need for more inclusive research and equitable implementation strategies."

Journal • Review • Gene Therapies • Hematological Disorders • Hemophilia • Pediatrics • Rare Diseases

Roctavian withdrawal: exploring the gap between innovation and healthcare system readiness in hemophilia A gene therapy. (PubMed, Res Pract Thromb Haemost) - "These dynamics reveal a gap between scientific innovation and healthcare delivery, suggesting that the barriers to gene therapy are not biological but structural. Addressing this gap will require not only technological advances but also sustainable reimbursement models, coordinated long-term follow-up infrastructure, and healthcare systems capable of supporting advanced therapies beyond their approval."

Journal • Review • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Vulnerability, protection and fairness: ethical and regulatory limits in small-N gene therapy trials. (PubMed, Trials) - "Current gene therapy trial frameworks largely succeed in supporting methodological flexibility for ultra-rare conditions but insufficiently operationalize fair inclusion. Ethical concerns arise not because participant protections are excessive, but because the burdens associated with necessary scientific and regulatory requirements may disproportionately affect patients facing structural disadvantages. Ensuring justice in ultra-rare gene therapy research requires extending proportionate, risk-based approaches beyond evidence generation to include the identification and mitigation of foreseeable barriers to participation."

Journal • Gene Therapies • Rare Diseases

Safety, Tolerability, and Efficacy Study of Valoctocogene Roxaparvovec in Hemophilia A With Active or Prior Inhibitors (clinicaltrials.gov) - P1/2 | N=10 | Completed | Sponsor: BioMarin Pharmaceutical | Active, not recruiting ➔ Completed | Trial completion date: Apr 2029 ➔ Apr 2026 | Trial primary completion date: Apr 2029 ➔ Apr 2026

Trial completion • Trial completion date • Trial primary completion date • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

European Healthcare Professionals and People with Haemophilia: Knowledge and Perspectives on Haemophilia Gene Therapy- Results of the EAHAD Gene Therapy Survey (ISTH 2026) - "Background Adeno-associated virus (AAV)-based gene therapies for haemophilia have transitioned to clinical practice following regulatory approval (valoctocogene roxaparvovec and etranocogene dexaparvovec, 2022– 2023)...These are essential to optimise shared decision-making and gene therapy integration into European haemophilia care. DOI*10.1016/j.rpth.2026.104785"

Gene therapy • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Budesonide supports FVIII Expression in Hemophilia A Gene‑Therapy Recipients (ISTH 2026) - "Aims To evaluate the long ‑ term efficacy and safety of a single infusion of valoctocogene roxaparvovec in adults with severe hemophilia A. Methods Both patients with severe hemophilia A received a single infusion of valoctocogene roxaparvovec at a dose of 6×10¹³ vector genomes/kg...Budesonide was introduced during the prednisone taper and kept for six months...In addition, budesonide served as a potent substitute for systemic steroids, possibly helping to maintain stable transgene expression. DOI*10.1016/j.rpth.2026.104794"

Gene therapy • CNS Disorders • Epilepsy • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Hepatitis B • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Rare Diseases

Biopsy-proven immune-mediated hepatitis after valoctocogene roxaparvovec. (PubMed, Haematologica) - "Immune-mediated hepatitis can cause ALT elevations in HA after valoctogene roxaparvovec and, in selected cases, a biopsy-proven diagnosis could support a safer and more effective therapeutic course of prednisone to maintain optimal transgene expression."

Journal • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Hepatitis C • Inflammation • Rare Diseases

Italian Patients Journey for Gene Therapy in Haemophilia A. (PubMed, Haemophilia) - "This product-specific operational pathway proposal provides Italian clinicians with a comprehensive framework for managing patients with HA treated with GT, acknowledging the evolving nature of this innovative therapy and the need for continuous evaluation of the proposed pathway. The present journey may need adaptation for other GT products."

Journal • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Real-world provider experiences with hemophilia A gene therapy: administration of valoctocogene roxaparvovec. (PubMed, Res Pract Thromb Haemost) - "As a newer treatment modality, workflows for gene therapy administration and postinfusion care are still unfamiliar to many health care professionals and may be perceived as implementation barriers. We are 10 hemophilia gene therapy providers across the United States, Italy, and Germany sharing our experiences of administering valoctocogene roxaparvovec in clinical practice to >25 patients with severe hemophilia A. In this study, we provide our insights into patient preparation, establishment of treatment centers and multidisciplinary teams, postinfusion management, and patient follow-up to facilitate open communication and collaboration among the treatment community."

Journal • Real-world evidence • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

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

Nonclinical Toxicity Study Duration in AAV Gene Therapy Development: Evidence from Industry Survey Supports Adequacy of Short-Term Assessments (ASGCT 2026) - "These findings aligned with regulatory reviews of approved AAV products (e.g., Zolgensma, Luxturna, Roctavian) that consistently demonstrated the adequacy of ≤3-month studies for approved and marketed products. Conclusion The outcome of this survey supports a risk-based, science-driven approach to in vivo study duration, emphasizing that shorter-term studies are generally sufficient for identifying relevant toxicities associated with AAV-based gene therapies. Embracing this approach can reduce animal use, accelerate development timelines, and support harmonized regulatory expectations for AAV gene therapy products."

Gene therapy • Gene Therapies

Gene Therapy in Hemophilia: Clinical Advances, Immunological Challenges, and Emerging Therapeutic Perspectives. (PubMed, Int J Mol Sci) - "In aggregate, these perspectives position gene therapy not as a singular curative event but as a component of an evolving, biologically integrated management strategy. Long-term follow-up translational research (LTFU) and coordinated global efforts will be essential to optimize durability, safety, and equitable access."

Journal • Review • Gene Therapies • Hematological Disorders • Hemophilia • Immune Modulation • Immunology • Rare Diseases

CORRELATION BETWEEN FACTOR VIII CHROMOGENIC ACTIVITY AND ANTIGEN LEVELS IN PATIENTS TREATED WITH AAV5-MEDIATED GENE THERAPY FOR HEMOPHILIA A. (PubMed, J Thromb Haemost) - "FVIII antigen levels showed strong concordance with CA results following AAV-mediated gene therapy. These findings support the chromogenic assay as the preferred method for monitoring therapeutic FVIII expression in patients treated with gene therapy for hemophilia A. Multi-assay strategies remain essential for comprehensive assessment of transgene expression and clinical management after gene therapy."

Journal • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Durability of efficacy, safety, and quality of life 5 years after valoctocogene roxaparvovec gene transfer for severe hemophilia A: final phase 3 GENEr8-1 trial results. (PubMed, Res Pract Thromb Haemost) - "No serious treatment-related adverse events occurred after year 1. Valoctocogene roxaparvovec provides durable hemostatic efficacy, FVIII activity, and improved health-related quality of life for ≥5 years, with no new safety signals."

HEOR • Journal • P3 data • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

From early promise to market withdrawal of valoctocogene roxaparvovec. (PubMed, Mol Ther) - No abstract available

Journal

Bringing Gene Therapy Into Real World Clinical Practice. (PubMed, Haemophilia) - "Despite its transformative potential, slow real-world adoption is observed, constrained by scientific, operational, and reimbursement challenges. Ongoing data collection via registries and harmonized monitoring pathways will be vital for optimizing outcomes and delineating long-term safety profiles for gene therapy in haemophilia clinical practice."

Journal • Real-world evidence • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Oncology • Rare Diseases

Final Analysis of the Phase 1/2 Trial of Valoctocogene Roxaparvovec for Severe Haemophilia A. (PubMed, Haemophilia) - P1/2 | "Over 7 years, valoctocogene roxaparvovec increased FVIII activity from baseline and improved haemostasis compared with FVIII prophylaxis for most participants. The 6 × 1013 vg/kg dose was more efficacious than 4 × 1013 vg/kg. No concerning long-term safety signals were identified."

Journal • P1/2 data • Cardiovascular • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Hepatology • Liver Failure • Rare Diseases

Treatment With Valoctocogene Roxaparvovec in a Patient With Severe Hemophilia A Led to Sustained Normal FVIII Levels. (PubMed, Haemophilia) - "Valoctocogene roxaparvovec can offer durable FVIII expression in severe hemophilia A. This case provides valuable insights into personalised immunosuppression therapy with a favourable outcome for long-term efficacy and safety."

Journal • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Musculoskeletal Diseases • Orthopedics • Rare Diseases

Current Status of Clinical Gene Therapy for Hemophilia and Globin Disorders. (PubMed, J Blood Med) - "In this review, we discuss each of the six therapies that now have regulatory approval for treatment in the United States: Roctavian (valoctocogene roxaparvovec) for hemophilia A, Beqvez (fidanacogene elaparvovec) and Hemgenix (etranacogene dezaparvovec) for hemophilia B, Lyfgenia (lovotibeglogene autotemcel) for sickle cell disease, Zynteglo (betibeglogene autotemcel) for β-thalassemia, and Casgevy (exagamglogene autotemcel) for either sickle cell disease or β-thalassemia. Overall, results are very encouraging, often freeing patients from the need for coagulation factor or red blood cell (RBC) infusions, albeit that for some of these diseases there is room for further improvement in terms of safety and therapeutic durability, which may be achieved with next-generation gene therapy products. However, improvements are needed to address issues with durability of results, side effects, and accessibility of these therapies."

Journal • Review • Beta-Thalassemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases • Sickle Cell Disease

BioMarin pulls hemophilia gene therapy Roctavian, taking $240M hit after divestiture efforts flounder (Fierce Pharma) - "The move follows a 'comprehensive effort' to identify a potential buyer for the therapy, BioMarin explained Monday in its fourth-quarter earnings...This decision resulted in charges of about $240 million over the fourth quarter of 2025, including a $119 million inventory write-off and $118 million in asset value impairments."

Commercial • Discontinued • Hemophilia A

Gene therapy in the treatment of hemophilia A: a systematic review and meta-analysis. (PubMed, Expert Rev Hematol) - "We conducted a systematic review and meta-analysis to evaluate the efficacy, effectiveness, and safety of GT versus factor VIII (FVIII) or emicizumab prophylaxis...Fourteen publications from five studies evaluated valoctocogene roxaparvovec, giroctocogene fitelparvovec, and dirloctocogene samoparvovec...Durability of FVIII expression and long-term safety require further investigation. This study was prospectively registered at PROSPERO (CRD42024562798)."

Journal • Retrospective data • Review • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Balancing Promise and Peril: Hemophilia Gene Therapy Insights. (PubMed, IUBMB Life) - "Over the past three decades, remarkable advancements have been made in hemophilia gene therapy, culminating in the approval of Valoctocogene roxaparvovec (ROCTAVIAN, AAV-FVIII) and Etranacogene dezaparvovec (HEMGENIX, AAV-FIX) for patients with severe HA and HB, respectively. Nevertheless, gene therapy poses questions regarding its long-term efficacy and safety. This review synthesizes findings from clinical trials, addresses persistent challenges in hemophilia gene therapy, and underscores the biological constraints and limitations inherent to viral vector-based approaches."

Journal • Review • Gene Therapies • Genetic Disorders • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases • Thrombosis

Overview of gene therapy for hemophilia: questions and answers to navigate the innovation. (PubMed, J Thromb Haemost) - "Recent phase III trials of valoctocogene roxaparvovec (hemophilia A) and etranacogene dezaparvovec (hemophilia B) have shown durable factor expression for up to 5 years, with the Factor IX-Padua variant enhancing treatment efficacy 5-8 fold. While challenges remain regarding long-term durability, immune responses, and standardized care pathways, current AAV-based therapies represent a transformative advance. Future developments including alternative vectors, enhanced factor variants, and gene editing technologies promise to further improve treatment outcomes and expand patient access."

Journal • Review • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases