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

Nonclinical toxicity study duration in AAV gene therapy development: Evidence from industry survey supports adequacy of short-term assessments. (PubMed, Mol Ther Methods Clin Dev) - "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. 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."

Journal • Gene Therapies

Deconstructing gene therapy in hemophilia for the clinician. (PubMed, Hematology Am Soc Hematol Educ Program) - "After decades of research, gene therapy for hemophilia is now commercially available for both hemophilia A and B. Currently, two products, valoctocogene roxaparvovec (for hemophilia A) and etranacogene dezaparvovec (for hemophilia B), have been licensed following approval in the United States and several other countries. This review's aims are (1) to deconstruct gene therapy in hemophilia and provide a basic framework for understanding its components and processes, including the transgene, the vector, and the delivery systems, in order to help clinicians present gene therapy as a treatment option in a shared decision-making model, better understand the clinical data, and explain gene therapy to their patients; (2) to gain knowledge of the currently approved gene therapies for hemophilia A and B, including their eligibility and exclusion criteria and the range of expected outcomes; and (3) to comprehend the shared decision-making process for these therapies and their..."

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

Long-term durability of rAAV gene therapy in hemophilia: Factor expression, clinical outcomes and underlying molecular mechanisms. (PubMed, Blood Rev) - "Approved therapies-valoctocogene roxaparvovec for hemophilia A and etranacogene dezaparvovec for hemophilia B-have demonstrated significant reductions in bleeding frequency and factor replacement requirements. Emerging strategies to enhance durability include next-generation vector design, codon optimization, gene editing technologies, and alternative delivery platforms. This review synthesizes current clinical evidence, biological understanding, and translational challenges, with an emphasis on strategies to optimize long-term efficacy of AAV-mediated gene therapy for hemophilia."

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

Bleeding Outcomes in Participants with Factor VIII Activity <5 IU/DL Post–Gene Transfer in GENEr8-1 (ASH 2023) - P3 | "Background: Valoctocogene roxaparvovec is expected to transfer a functional FVIII coding sequence that would eliminate the need for regular prophylaxis for people with severe hemophilia A (HA)...RTP was defined per-protocol as usual FVIII prophylaxis administered ≥1 time/week for ≥4 consecutive weeks or ≥2 emicizumab injections/month... Most participants with low FVIII activity had low bleeding rates, suggesting that low endogenous FVIII expression may provide protective hemostatic benefits. Many participants who resumed prophylaxis had clinical presentation consistent with moderate hemophilia; the individual decision to RTP was multifactorial and influenced by FVIII activity, bleeding rates, desired physical activity levels, and personal preferences."

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

Valoctocogene Roxaparvovec Estimated Long-Term Durability of Treatment Effect: An Extrapolation of the Most Recent Clinical Data (ASH 2024) - "In the scenario where 270-201 data were also used for the extrapolation, median estimated durability is estimated to range from 13.2–20.4 years. Conclusions : This analysis demonstrates that the observed therapeutic benefit is expected to be sustained beyond the 7 years of follow-up in existing clinical trials, illustrating the full treatment benefit that valoctocogene roxaparvovec can bring to PwSHA."

Clinical data • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Biomarin plans to sell rights to hemophilia A therapy Roctavian (Hemophilia News Today) - "Roctavian is currently approved in the U.S. and Europe for the treatment of certain adults with severe hemophilia A. Last year, Biomarin announced that, in an effort to make the therapy more profitable, it was limiting sales of Roctavian to three countries: Italy, Germany, and the U.S."

Commercial • Hemophilia A

Engineered coagulation factor VIII with enhanced secretion and coagulation potential for hemophilia A gene therapy. (PubMed, Blood) - "In macaques, the administration of AAV5 vector carrying the engineered FVIIISQ without CpG sequences resulted in a supra-physiological increase in plasma FVIII activity at a dose one-thirtieth that of valoctocogene roxaparvovec (2 × 1012 vg/kg). The engineered FVIIISQ may thus provide stable, long-term therapeutic efficacy in AAV-mediated hemophilia A gene therapy even at low doses."

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

Improving rAAV production: key adenoviral elements and their impact on vector yield and quality (ESGCT 2024) - "Recombinant Adeno-associated viruses (AAVs) are one of the most used viral vectors for gene therapy, with several products already on the market (e.g., Hemgenix, Roctavian, Elevidys). A smaller plasmid, without adenoviral structural proteins was generated, allowing a similar or better rAAV production across all tested serotypes. The knowledge generated from this study will ultimately facilitate the development of improved strategies for the large-scale production of high-titer and high-quality rAAV vectors, thereby advancing the gene therapy field."

Gene Therapies

Today, the company announced its plan to pursue options to divest ROCTAVIAN, including exploring out-licensing opportunities. (PRNewswire) - "BioMarin plans to continue to make ROCTAVIAN commercially available in the U.S., Italy and Germany until next steps are finalized. The company will continue to provide support and monitoring for people treated with ROCTAVIAN."

Discontinued • Hemophilia A

Cost-effectiveness of emicizumab for the treatment of hemophilia A: a systematic review. (PubMed, Front Public Health) - "In addition, rFVIIIFc and valoctocogene roxaparvovec were more cost-effective than emicizumab for people with HA without inhibitors. Cost-effectiveness analyses with more accurate cost estimations of different countries should provide more convincing evidence for clinical decision-making. Identifier CRD 42023429349, https://www.crd.york.ac.uk/PROSPERO/view/CRD42023429349."

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

GENEr8-3: Study to Evaluate the Efficacy and Safety of Valoctocogene Roxaparvovec, With Prophylactic Steroids in Hemophilia A (clinicaltrials.gov) - P3 | N=22 | Completed | Sponsor: BioMarin Pharmaceutical | Active, not recruiting ➔ Completed | Trial completion date: Jan 2027 ➔ May 2025

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

Estimated Long-Term Durability of Valoctocogene Roxaparvovec Treatment in Male patients with Severe Hemophilia A: An Extrapolation of Clinical Data. (PubMed, Adv Ther) - P1/2, P3 | "This analysis demonstrates the potential therapeutic benefit of valoctocogene roxaparvovec may be sustained beyond the follow-up period in existing clinical trials and across all parametric extrapolations and definitions analyzed, indicating that gene therapy may offer long-term benefits beyond what has been previously reported (i.e., 7 years)."

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

Comparative Effectiveness of Valoctocogene Roxaparvovec and Efanesoctocog Alfa in the Treatment of Severe Hemophilia A: A Matching-Adjusted Indirect Comparison of Bleeding Frequency. (PubMed, Adv Ther) - "This MAIC suggests that valoctocogene roxaparvovec provides a greater likelihood of patients experiencing zero treated bleeds compared with efanesoctocog alfa during the first year following treatment initiation."

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

Advances in Gene Therapy Clinical Trials for Hemophilia Care. (PubMed, Curr Gene Ther) - "Recent advances in adeno-associated virus (AAV)-mediated gene transfer, particularly the approvals of valoctocogene roxaparvovec (Roctavian) and etranacogene dezaparvovec (Hemgenix), mark significant milestones in hemophilia care. The review also addresses the critical need for equitable access and scalable production models to ensure global availability of gene therapies. With ongoing innovation and multidisciplinary collaboration, gene therapy is poised to transition from experimental intervention to mainstream curative care in hemophilia and other hematologic diseases."

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

Curative Therapies for Hemophilias and Hemoglobinopathies in Adults: Immune, Gene, and Stem Cell Approaches in a Global Context. (PubMed, Biomedicines) - "Recent advances in immune-based therapeutics (e.g., emicizumab, concizumab, crizanlizumab), viral vector-mediated gene addition (e.g., Roctavian, Hemgenix), and gene-modified autologous stem cell therapies (e.g., Zynteglo, Casgevy) have ushered in a new era of disease-modifying and potentially curative interventions. Equitable access, particularly in regions bearing the highest disease burden, will require collaborative funding strategies, regional capacity building, and inclusive regulatory frameworks. This review summarizes the current landscape of curative therapy, outlines implementation barriers, and calls for coordinated international action to ensure that transformative care reaches all affected individuals worldwide."

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

A Paradigm Shift in Hemophilia Care: The Promise of Gene Therapy. (PubMed, Curr Gene Ther) - "Gene therapy has shown new possibilities in hemophilia, with many patients achieving near-normal levels of clotting factors and experiencing a significant reduction in bleeding episodes. However, challenges remain, including potential declines in Factor VIII levels over time, immune responses to viral vectors, and high treatment costs. Ongoing research is focused on improving durability, expanding eligibility, and exploring alternative delivery methods."

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

Fitusiran (Qfitlia) for hemophilia A and B. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

BioMarin’s ROCTAVIAN Shows Sustained Efficacy, Safety Over 5 Years for Severe Hemophilia A (Yahoo Finance) - P3 | N=144 | GENEr8-1 (NCT03370913) | Sponsor: BioMarin Pharmaceutical | "On June 24, BioMarin Pharmaceutical Inc. presented new 5-year data from its Phase 3 GENEr8-1 trial at the 33rd Congress of the International Society on Thrombosis and Haemostasis/ISTH in Washington, D.C., which took place from June 21 to 25....FVIII activity remained consistent with previously reported results. Importantly, no new safety signals were observed over the 5-year study period. Across all 134 participants who received ROCTAVIAN in the study, there were no cases of FVIII inhibitors or thromboembolic events, and no treatment-related malignancies were observed."

P3 data • Hemophilia A

First Data from the American Thrombosis and Hemostasis Network Transcends Registry Hemophilia Gene Therapy Outcomes Arm (ISTH 2025) - P | "Background Adeno-associated viral vector (AAV)-mediated gene therapy for hemophilia B (HB) and hemophilia A (HA) is a reality for patients since conditional approval for marketing of etranacogene dezaparvovec-drlb and fidanacogene elaparvovec-dzkt for HB, and valoctocogene roxaparvovec-rvox for HA. Three participants required steroid treatment for vector-induced transaminitis. Table or Figure Upload"

Gene therapy • Cardiovascular • Dermatology • Fatigue • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Pain • Rare Diseases • Thrombosis • Urticaria

Final analysis of the phase 1/2 trial of valoctocogene roxaparvovec for severe hemophilia A (ISTH 2025) - "No serious TRAEs occurred after Y1. No participants had thromboembolic events or developed FVIII inhibitors."

P1/2 data • Cardiovascular • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Emicizumab provides excellent brain protection in a large unbiased retrospective cohort (ISTH 2025) - "Additionally, 7 patients participated in clinical trials, receiving either valoctocogene roxaparvovec (n = 4), BIVV001 (n = 1) or Mim8 (n = 2) (Figure 1). In contrast, two intracranial bleeds occurred in patients on FVIII prophylaxis, one of which was fatal. Table or Figure Upload"

Retrospective data • Cerebral Hemorrhage • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

VARIABILITY IN FVIII TRANSGENE EXPRESSION AMONG PATIENTS TREATED WITH VALOCTOCOGENE ROXAPARVOVEC (ISTH 2025) - "These patients were previously on prophylaxis with FVIII extended half-life products and emicizumab. However, one patient exhibited elevated alanine aminotransferase levels at week 7, for whom immunosuppressive therapy is ongoing. Table or Figure Upload"

Clinical • Cardiovascular • Fibrosis • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Hepatology • Immunology • Liver Failure • Rare Diseases • Thrombosis

Efficacy safety and quality of life 5 years after valoctocogene roxaparvovec gene transfer (ISTH 2025) - P3 | "Efficacy outcomes will include FVIII activity, bleeding and FVIII infusion rates, population- and participant-level insights into return to prophylaxis, and health-related quality of life. Updated safety data, including adverse events and corticosteroid use, will also be presented."

Clinical • HEOR • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Human Immunodeficiency Virus • Infectious Disease • Rare Diseases

Impact of valoctocogene roxaparvovec on hemophilia-free mind: A visual multidimensional method (ISTH 2025) - "Applying the thresholds to the GENEr8-1 trial data, the proportion of participants achieving HFM thresholds increased from baseline to Week 104 in each dimension (Figure 1). Increases ranged from +15% in the domains of ‘Joint Pain’ and ‘Affected Family Members and Caregivers’ to +42% in ‘Bleeding Benefit’ and +73% in ‘Injection Schedule’."

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

Comparing Gene Therapy in Hemophilia A with Generative AI (ISTH 2025) - "Aims Indirect comparation between Valactocogene R versus Giroctocogene F Background Gene therapy in haemophilia A -Valoctocogene Roxaparvovec (VR)- is a reality...The ↑ ALT indicates differences in safety profile in favour of GF (p 0.0012), although % of AFFINE patients with prophylactic anticoagulation (30.7%) is noteworthy. No statistical difference (p 0.193, Z-stadistic) in % of reduction of spontaneous bleeding (81.3% vs. 73.7%) Table or Figure Upload"

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