Gene Transfer with Etranacogene dezaparvovec (AAV5-Padua hFIX variant) in Adults with Severe or Moderate-Severe Hemophilia B: Two Year Data from a Phase 2b Trial

Miesbach, Wolfgang; Giermasz, Adam; Castaman, Giancarlo; Key, NS; Lattimore, SU; Leebeek, Frank W.G.; Drygalski, Annette von; Recht, Michael; Gomez, Esteban; Gut, Robert; Pipe, SW

doi:10.1055/s-0041-1728090

Cited by 5 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Final 18-month data from the phase 3 study with Etranacogene dezaparvovec showed FIX increases to 39% (6-month time point) and 37% (18 months) for HB gene therapy. 27 Use of factor concentrates decreased by 97% and the ABR by 64% in this study. Furthermore, patients with pre-existing NA against AAV were not excluded in this study, nevertheless 52 of 54 treated patients achieved a stable FIX expression.…”

Section: Methodsmentioning

confidence: 43%

“…In patients treated with Etranacogene dezaparvovec, 17% had an increase in liver enzymes. 27 The average duration of treatment with corticosteroids was 79 days and completed in all patients by week 26.…”

Section: Methodsmentioning

confidence: 99%

“…Die finalen 18-Monats-Daten der Phase-3-Studie mit Etranacogene dezaparvovec zeigen für die Gentherapie der Hämophilie B einen FIX-Anstieg auf 39% (Zeitpunkt 6 Monate) und 37% (18 Monate). 27 Der Gebrauch an Faktorkonzentraten ging in dieser Studie um 97%, die ABR um 64% zurück. In dieser Studie waren Patienten mit vorbestehenden NA gegen AAV nicht ausgeschlossen, dennoch erreichten 52 von 54 behandelten Patienten eine stabile FIX-Expression.…”

Section: Methodikunclassified

“…Bei den mit Etranacogene dezaparvovec behandelten Patienten hatten 17% einen Anstieg der Leberwerte. 27 Die durchschnittliche Behandlungsdauer mit Kortikosteroiden betrug 79 Tage und war bei allen Patienten bis Woche 26 beendet.…”

Section: Methodikunclassified

See 3 more Smart Citations

Gentherapie der Hämophilie: Empfehlung der Gesellschaft für Thrombose- und Hämostaseforschung (GTH)

et al. 2022

View full text Add to dashboard Cite

Gene therapy has recently become a realistic treatment perspective for patients with haemophilia. Reviewing the literature and our personal experience from clinical trials, we discuss key aspects of haemophilia A and B gene therapy with vectors derived from adeno-associated virus (AAV), including predictable results, risks, adverse events, and patient-reported outcomes. Patient selection, informed consent, administration, and monitoring of gene therapy as well as data collection are explained. We also discuss the need for interdisciplinary cooperation with hepatology and other specialties. We emphasize structural and organizational requirements for treatment centres according to the hub-and-spoke model and recommend the use of electronic diaries to ensure safe and timely collection and exchange of data. Electronic diaries will play a key role as primary source of data for pharmacovigilance, post-marketing clinical studies, national and international registries, as well as health technology and benefit assessment. Reimbursement aspects and the future of gene therapy in adolescents and children are also considered. In a rapidly evolving scientific environment, these recommendations aim to support treatment providers and payers to prepare for the implementation of gene therapy following marketing authorization.

show abstract

Section: Methodsmentioning

confidence: 43%

Section: Methodsmentioning

confidence: 99%

Section: Methodikunclassified

See 2 more Smart Citations

Gentherapie der Hämophilie: Empfehlung der Gesellschaft für Thrombose- und Hämostaseforschung (GTH)

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Gene therapy is a new and evolving therapeutic modality for hemophilia. Clinical trials have established the efficacy of gene therapy in decreasing bleeding and use of hemostatic treatment (Miesbach et al, 2022; Ozelo et al, 2022). However, many questions will remain unresolved about the long‐term safety, variability and durability of efficacy at the completion of current ongoing clinical trial programs.…”

Section: Case Studiesmentioning

confidence: 99%

Data sharing to advance gene‐targeted therapies in rare diseases

Lekstrom-Himes

Augustine

Brower

et al. 2023

American J of Med Genetics Pt C

View full text Add to dashboard Cite

Recent advancements in gene‐targeted therapies have highlighted the critical role data sharing plays in successful translational drug development for people with rare diseases. To scale these efforts, we need to systematize these sharing principles, creating opportunities for more rapid, efficient, and scalable drug discovery/testing including long‐term and transparent assessment of clinical safety and efficacy. A number of challenges will need to be addressed, including the logistical difficulties of studying rare diseases affecting individuals who may be scattered across the globe, scientific, technical, regulatory, and ethical complexities of data collection, and harmonization and integration across multiple platforms and contexts. The NCATS/NIH Gene‐Targeted Therapies: Early Diagnosis and Equitable Delivery meeting series held during June 2021 included data sharing models that address these issues and framed discussions of areas that require improvement. This article describes these discussions and provides a series of considerations for future data sharing.

show abstract

Stable and durable factor IX levels in patients with hemophilia B over 3 years after etranacogene dezaparvovec gene therapy

et al. 2023

View full text Add to dashboard Cite

Etranacogene dezaparvovec (AMT-061) is a recombinant adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX (FIX) transgene with a liver-specific promoter. Here we report 3-year outcomes from a Phase 2b, open-label, single-dose, single-arm, multi-center trial (NCT03489291) conducted in adults with severe or moderately severe hemophilia B (FIX ≤2%). All participants (n=3) received a single intravenous dose (2×1013 gene copies/kg) and will be followed for 5 years. The primary endpoint of FIX activity ≥5% at 6 weeks was met (mean 30.6% [min-max, 23.9%-37.8%]). Secondary endpoints included bleed frequency, FIX concentrate use, joint health, and adverse events (AEs). All participants required routine FIX prophylaxis and had neutralizing antibodies to AAV5 (mean titer at screening=39) prior to etranacogene dezaparvovec treatment. Post administration, FIX activity rose to a mean of 40.8% (min-max, 31.3%-50.2%) at year 1, sustained at year 3 (mean 36.9% [min-max, 32.3%-41.5%]). All participants discontinued FIX prophylaxis. Complete elimination of bleeds occurred in 2/3 participants. One participant required on-demand FIX replacement therapy post treatment per protocol due to elective surgeries, for 2 reported bleeding episodes, and twice for a single self-administered infusion due to an unreported reason. One participant experienced 2 mild, self-limiting AEs shortly after dosing. During the 3-year study period, there were no clinically significant elevations in liver enzymes, no requirement for steroids, no FIX inhibitor development, and no late emergent safety events in any participant. Etranacogene dezaparvovec was safe and effective in adults with hemophilia B through 3 years post-administration. ClinicalTrials.gov Identifier: NCT03489291.

show abstract

Gene Transfer with Etranacogene dezaparvovec (AAV5-Padua hFIX variant) in Adults with Severe or Moderate-Severe Hemophilia B: Two Year Data from a Phase 2b Trial

Cited by 5 publications

References 0 publications

Gentherapie der Hämophilie: Empfehlung der Gesellschaft für Thrombose- und Hämostaseforschung (GTH)

Gentherapie der Hämophilie: Empfehlung der Gesellschaft für Thrombose- und Hämostaseforschung (GTH)

Data sharing to advance gene‐targeted therapies in rare diseases

Stable and durable factor IX levels in patients with hemophilia B over 3 years after etranacogene dezaparvovec gene therapy

Contact Info

Product

Resources

About