AMT-060 / uniQure - LARVOL DELTA

Stable Factor IX Expression and Sustained Reductions in Factor IX Use 8 Years after Gene Therapy with CSL220 (Formerly AMT-060) in Adults with Hemophilia B (ASH 2024) - P, P1/2 | "Conclusions : Durability of factor expression is a key consideration in the decision-making process about gene therapy for patients and physicians. With just one amino acid difference in the expressed FIX protein, CSL220 is the precursor of etranacogene dezaparvovec (CSL222), which was the first gene therapy approved for the treatment of hemophilia B. This 8-year follow-up after CSL220 administration provides continued evidence for the durability, stability, and safety of FIX expression after AAV5-based gene therapy for the treatment of hemophilia B."

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

Stable factor IX expression and sustained reductions in factor IX use 7 years after gene therapy with AMT-060 in adults with haemophilia B (ESGCT 2024) - No abstract available

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

Etranacogene dezaparvovec hemophilia B gene therapy phase 2b trial final results: stable and durable FIX level expression over 5 years (ISTH 2024) - P, P2 | "All 3 participants had neutralizing antibodies (NAbs) to AAV5 at mean titer of 25 at dosing. Mean aPTT-based FIX activity remained stable throughout the trial duration: from Year 1 (40.7%) to Year 5 (46.7%). At Year 5 post-dose, FIX activity measured 46.8%, 39.0% and 51.2% in the 3 participants, respectively."

Clinical • Gene therapy • P2b data • Cardiovascular • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

First report of a long-term follow-up extension study 6 years after gene therapy with AMT-060 in adults with hemophilia B confirms safety and stable FIX expression and sustained reductions in factor IX use (EAHAD 2024) - No abstract available

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

Immunoadsorption Plasmapheresis for the removal of plasma immunoglobulins to enable repeat can administration with an AAV5 gene therapy vector (GTH 2024) - "All 5 animals were challenged with the exact same AAV5 capsid encoding a different protein, human factor IX (AAV5-hFIX) at a dose of 6E13 vg/kg, administered within 10 minutes of the last run IAP...As such, IAP may enable AAV-based vector gene therapy in patients currently excluded from gene therapy clinical trials or commercial product use due to pre-existing antibodies. Furthermore, additional evaluation of the efficacy of this procedure may be worthwhile in subjects with pre-existing antibody titers resulting from natural exposure to AAV infections, which result in lower antibody titers than the treatment-emergent titers observed here."

Gene therapy • Gene Therapies • Hematological Disorders • Immune Modulation • Immunology • Infectious Disease • ACACA

Study of AAV5-hFIX in Severe or Moderately Severe Haemophilia B (clinicaltrials.gov) - P=N/A | N=9 | Active, not recruiting | Sponsor: CSL Behring

Trial completion date • Trial primary completion date • Viral vector • Hematological Disorders • Hemophilia • Rare Diseases

Etranacogene dezaparvovec for the treatment of adult patients with severe and moderately severe hemophilia B. (PubMed, Expert Rev Hematol) - "However, long-term data are required to ascertain the durability of FIX levels achieved and safety. The cost-effectiveness and adoption of innovative payment models for reimbursement are key in choosing gene therapy over existing treatments."

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

Assessing the safety profile of AMT-060 and etranacogene dezaparvovec gene therapies across clinical trials in people with severe/moderately severe hemophilia B (ISTH 2023) - P1/2, P2b, P3 | "Seven participants experienced infusion-related reactions; three required temporary dose interruptions, four received supportive care (including antihistamines, corticosteroids, narcotics, epinephrine) and one discontinued treatment after partial dosing (~10%).In Phase 2b, there were two TRAEs in one participant (headache; elevated C-reactive protein), that resolved without intervention, and one SAE unrelated to treatment (worsening of pre-existing avascular necrosis)... Across studies, all participants experienced ≥1 AE; most mild (Table), with no FIX inhibitor development or T-cell responses. In HOPE-B, 38 participants (70.4%) experienced 93 treatment-related AEs (TRAEs) and no treatment-related serious AEs (SAEs); a SAE of hepatocellular carcinoma was assessed as unrelated to treatment. There was one death, also assessed as unrelated to treatment."

Clinical • Gene therapy • Gastrointestinal Cancer • Gene Therapies • Hematological Disorders • Hemophilia • Hepatocellular Cancer • Oncology • Pain • Rare Diseases • Solid Tumor • CRP

Immunoadsorption Plasmapheresis for the Removal of Plasma Immunoglobulins to Enable Repeat Dose Administration with an AAV5 Gene Therapy Vector (ASGCT 2023) - "All 5 animals were challenged with the exact same AAV5 capsid encoding a different protein, human factor IX (AAV5-hFIX) at a dose of 6E13 vg/kg, administered within 10 minutes of the last run IAP...As such, IAP may enable AAV-based vector gene therapy in patients currently excluded from gene therapy clinical trials or commercial product use due to pre-existing antibodies. Furthermore, additional evaluation of the efficacy of this procedure may be worthwhile in subjects with pre-existing antibody titers resulting from natural exposure to AAV infections, which result in lower antibody titers than the treatment-emergent titers observed here."

Gene therapy • Gene Therapies • Hematological Disorders • Immune Modulation • Immunology • Infectious Disease • ACACA

Durability of Factor IX Activity and Bleeding Rate in People with Severe or Moderately Severe Hemophilia B after 5 Years of Follow-up in the Phase 1/2 Study of AMT-060, and after 3 Years of Follow-up in the Phase 2b and 2 Years of Follow-up in the Phase 3 Studies of Etranacogene Dezaparvovec (AMT-061) (ASH 2022) - P1/2, P2b, P3 | "Gene therapy for hemophilia B appears to have a durable response. Across the Phase 1/2 study of AMT-060 and the Phase 2b and Phase 3 studies of etranacogene dezaparvovec, FIX activity levels are sustained throughout the observation period. Reductions in bleeding events also remained stable across the course of the three studies."

P1/2 data • P2b data • P3 data • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

[VIRTUAL] AMT-060 Gene Therapy in Adults with Severe or Moderate-Severe Hemophilia B Confirm Stable FIX Expression and Durable Reductions in Bleeding and Factor IX Consumption for up to 5 Years (ASH 2020) - P1/2 | "Background: Gene therapy aims to provide long-term therapeutic benefit from a single administration. There were no additional safety concerns with longer term follow-up. This data supports the ongoing Phase 3 study of the enhanced construct etranacogene dezaparvovec (AMT-061), which encodes the highly active Padua FIX variant."

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

Clearance of Vector DNA Following Systemic Administration of AAV5-hFIX or AAV5-hFIX Padua in Patients with Severe or Moderate-Severe Hemophilia B (ASH 2019) - P1/2, P2b; "Introduction Current adeno-associated viral (AAV) vector-based gene therapy strategies for hemophilia rely on systemic administration of the vector. As expected, AMT-061 vector DNA was detectable at 36 weeks in blood and in the semen of 1 of 3 participants, although clearance had not yet been established in the remaining participants. The presence of vector DNA in bodily fluids assessed was not associated with any adverse safety or efficacy findings."

Clinical • PCR

Stable FIX Expression and Durable Reductions in Bleeding and Factor IX Consumption for up to 4 Years Following AMT-060 Gene Therapy in Adults with Severe or Moderate-Severe Hemophilia B (ASH 2019) - P1/2; "Long-term stable endogenous FIX activity and reductions in ABR and FIX replacement use were observed following a single treatment with AMT-060. There were no additional safety concerns with longer term follow-up. These findings support the ongoing Phase III study of the enhanced construct, AMT-061, which encodes the highly active Padua FIX variant."

Clinical

Reduction in Annualized Bleeding and Factor IX Consumption up to 2.5 Years in Adults with Severe or Moderate-Severe Hemophilia B Treated with AMT-060 (AAV5-hFIX) Gene Therapy (ASH 2018) - P1/2; "In addition, we have observed continued reductions in annualized bleeds to near zero with the higher dose of AMT-060, and a 78-93% reduction in exogenous FIX use. The lack of additional safety concerns or treatment-related adverse events over the longer study period, including no recurring changes in ALT, support the continued development and transition of AMT-060 to AMT-061, which will use the same AAV5 vector to deliver the 2×1013 gc/kg dose with the enhanced Padua transgene, which is anticipated to increase FIX activity 6-8 fold."

Clinical • Biosimilar • Gene Therapies • Genetic Disorders • Hematological Disorders • Hemophilia

DURABILITY OF RESPONSE AFTER LONG-TERM FOLLOW-UP IN THE PHASE 1/2 STUDY OF AMT-060, AND PHASE 2B AND 3 STUDIES OF ETRANACOGENE DEZAPARVOVEC IN HAEMOPHILIA B (EAHAD 2023) - P1/2, P2b, P3 | "Gene therapy for HB appears to have a durable response. In the Phase 1/2 study of AMT-060 and Phase 2b and 3 studies of etranacogene dezaparvovec, FIX activity was sustained and reductions in bleeding events remained stable."

P1/2 data • P2b data • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Durability of Factor IX Activity and Bleeding Rate in People With Severe or Moderately Severe Haemophilia B After Long-term Follow-Up in the Phase 1/2 Study of AMT-060, and Phase 2b and Phase 3 Studies of Etranacogene Dezaparvovec (AMT-061 ) (#113) (GTH 2023) - P1/2, P2b, P3 | "Conclusion Gene therapy for HB appears to have a durable response. In the Phase 1/2 AMT-060 study and the Phase 2b and Phase 3 etranacogene dezaparvovec studies, FIX activity is sustained and reductions in bleeding events remain stable."

P1/2 data • P2b data • P3 data • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Study of AAV5-hFIX in Severe or Moderately Severe Haemophilia B (clinicaltrials.gov) - P1/2 | N=9 | Active, not recruiting | Sponsor: CSL Behring

New P1/2 trial • Hematological Disorders • Hemophilia • Rare Diseases

Five-Year Data Confirm Stable FIX Expression and Sustained Reductions in Bleeding and Factor IX Use Following AMT-060 Gene Therapy in Adults with Severe or Moderate–Severe Hemophilia B (GTH 2022) - P1/2 | "Sustained endogenous FIX activity and reductions in ABR and use of FIX replacement were maintained through 5 years following a single administration of AMT-060, with no additional safety concerns. Participants are being offered enrolment in a long-term follow-up study over a further 5 years. A Phase 3 study of the enhanced construct etranacogene dezaparvovec (AMT-061) is ongoing."

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

[VIRTUAL] Five Year Data Confirms Stable FIX Expression and Sustained Reductions in Bleeding and Factor IX Use Following AMT-060 Gene Therapy in Adults with Severe or Moderate-severe Hemophilia B (ISTH 2021) - P1/2 | "Background : Gene therapy in hemophilia aims to provide long-term therapeutic benefit from a single administration. Participants are being offered enrolment in a long term follow up study over a further 5 years. Phase 3 study of the enhanced construct etranacogene dezaparvovec (AMT-061) is ongoing."

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

uniQure Announces Presentations at Upcoming International Society on Thrombosis and Haemostasis (ISTH) Virtual Congress (BioSpace) - "uniQure...announced that eight data presentations, of which three are oral presentations, will be delivered at the International Society on Thrombosis and Haemostasis (ISTH) Virtual Congress being held July 17-21, 2021."

Clinical data • Hemophilia

[VIRTUAL] Dynamics, Features and Cross-Reactivity of IgG Pool Induced after AAV5 Gene Therapy for Hemophilia B (ASGCT 2021) - "Interestingly, IgG3 subclass was detected only after AAV5-hFIX administration and showed low cross-reactivity with a preferential affinity for AAV5. Further studies on post gene therapy samples and deeper epitope mapping analysis are envisaged to define the nature of the cross-reactivity between AAV5 and other serotypes and thus confirm the peculiar immunological profile of AAV serotype 5."

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

Trial of AAV5-hFIX in Severe or Moderately Severe Hemophilia B (clinicaltrials.gov) - P1/2; N=10; Completed; Sponsor: UniQure Biopharma B.V.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Hematological Disorders • Hemophilia • Rare Diseases • CCL2 • IL2 • IL6

[VIRTUAL] AMT‐060 GENE THERAPY IN ADULTS WITH SEVERE OR MODERATE‐SEVERE HEMOPHILIA B CONFIRM STABLE FIX EXPRESSION AND SUSTAINED REDUCTIONS IN BLEEDING FOR UP TO 5 YEARS (EAHAD 2021) - P1/2 | "Durable, stable endogenous FIX activity and reductions in ABR and FIX replacement use were maintained over several years following a single treatment with AMT-060. There were no additional safety concerns with longer term follow-up. These data support the ongoing Phase 3 study of the enhanced construct etranacogene dezaparvovec (AMT-061), which encodes the highly active Padua FIX variant."

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

uniQure to Participate in Multiple Upcoming Industry Conferences in February (GlobeNewswire) - "14th Annual Congress of the European Association of Hemophilia and Allied Disorders (EAHAD), February 3 – 5, 2021...uniQure will deliver multiple presentations on the company’s gene therapy candidate etranacogene dezaparvovec in patients with hemophilia B. These presentations will include encore clinical data first presented at medical conferences late last year, as well as health economic data....65th Annual Meeting of the Society of Thrombosis and Haemostasis Research (GTH), February 22 – 26, 2021...Professor Wolfgang Miesbach...will present two-year follow-up data on etranacogene dezaparvovec in hemophilia B, as well as five-year follow-up data on AMT-060, also in patients with hemophilia B."

Clinical data • Hemophilia

[VIRTUAL] AMT-060 Gene Therapy in Adults with Severe or Moderate-Severe Hemophilia B Confirms Stable FIX Expression and Sustained Reductions in Bleeding for up to 5 Years (GTH 2021) - P1/2 | "Background and Objective Gene therapy aims to provide long-term therapeutic benefit from a single administration. There were no additional safety concerns with longer term follow-up. This data supports the ongoing Phase 3 study of the enhanced construct etranacogene dezaparvovec (AMT-061), which encodes the highly active Padua FIX variant."

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