• ClinicalTrials.gov Identifier: NCT03489291¹
• Phase IIb, Open-label, Single-dose, Single-arm Study

• Active, not recruiting, P3 trial ongoing¹
• Last Update Posted: February 21, 2023

• Individuals with detectable anti-AAV5 NAb (luciferase assay) included
• 3/3 subjects with positive NAb titers participants had no anti-AAV5 IgGantibodies at screening or baseline²
• Male ≥ 18 years with known severe FIX deficiency (< 1% of normal circulating FIX)
• >20 previous EDs of treatment with FIX protein

• ALT, AST and total bilirubin > 2 times UNL
• Previous gene therapy treatment
• Find full exclusion criteria listed on the supplemental data²

AAV5, Insect cells, baculovirus expression system²

Codon-opimized FIX-Padua²

• LP1 that is a smaller variant of the originally constructed APOE-HCR/hAAT enhancer/promoter³
• LP1 is also used in AMT-060 vector (AAV5-wt FIX)⁴

Systemic⁵

2e13 (n = 3)

• A planned 26-weeks interim assessment is reported here²
• The 1-year  follow-up is reported here⁶
• The 3-year outcomes of the Phase 2b trial are published here⁷ 
• Additional long-term follow-up assessments for 5 years were planned^6-7

OS

Early outcomes related to FIX activity are taken from here^2, 6 and summarized as follows: 

Subsequently, 3-year outcomes related to FIX activity after gene transfer were reported here⁷ and summarized as follows:

According Figure 1 included in that publication⁶:

• Peak in P1 and P3 (higher FIX levels) observed between W14 - W22 
• Peak in P2 (lower FIX levels) observed at W26

• As of 26² and 36⁶ weeks, there were no bleeds post-treatment
• As reported in the 3-year outcomes article⁷:
  • 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

• As of 36 weeks, there was no requirement for FIX replacement aside from protocol-specified use for perioperative management in P3⁶
• The 3-year outcomes reported in this article⁷ revealed the following observations:
  • All participants discontinued FIX prophylaxis
  • 1/3 of the pts. required on-demand FIX replacement therapy post-treatment, as per the protocol

No infusion related reactions were reported

In P1, 2 AEs possibly related to etranacogene dezaparvovec were reported here^2, 6 as follows:

• Self-limiting headache on day of dosing
• Mild elevation in CRP level (7.4 mg/L; reference range, 0-3 mg/L) on day 14 post treatment that resolved without intervention

Notably, the published 3-year outcomes of the Phase 2b trial⁷ did not report any additional AEs 

Not reported

• 1/3 pts. (P1), non-clinically significant (44 IU/L at week 22)²
• No pts. required steroids related to the treatment^2, 6-7

1/3 pts. (P2), non-clinically significant (43-48 IU/L at weeks 2 and 4)²

In 3/3 pts., no T-cell-mediated anti-AAV5 capsid responses were detected during W1 through W26²

Not applicable (resolved without steroid treatment)^2, 6

No^2, 6

Not reported

1. Dose Confirmation Trial of AAV5-hFIXco-Padua. Available at: Study Details | Dose Confirmation Trial of AAV5-hFIXco-Padua | ClinicalTrials.gov
2. Von Drygalski, A., et al., Etranacogene dezaparvovec (AMT-061 phase 2b): normal/near normal FIX activity and bleed cessation in hemophilia B. Etranacogene dezaparvovec (AMT-061 phase 2b): normal/near normal FIX activity and bleed cessation in hemophilia B - PubMed (nih.gov)
3. Nathwani, A.C., et al., Self-complementary adeno-associated virus vectors containing a novel liver-specific human factor IX expression cassette enable highly efficient transduction of murine and nonhuman primate liver. Blood, 2006. 107(7): p. 2653-61. Self-complementary adeno-associated virus vectors containing a novel liver-specific human factor IX expression cassette enable highly efficient transduction of murine and nonhuman primate liver | Blood | American Society of Hematology (ashpublications.org)
4. Miesbach, W., et al., Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B. Blood, 2018. 131(9): p. 1022-1031. Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B - PubMed (nih.gov)
5. Nathwani, A.C., Gene therapy for hemophilia. Hematology Am Soc Hematol Educ Program, 2019. 2019(1): p. 1-8. Gene therapy for hemophilia - PubMed (nih.gov)
6. Pipe, S., et al., One Year Data from a Phase 2b Trial of AMT-061 (AAV5-Padua hFIX variant), an Enhanced Vector for Gene Transfer in Adults with Severe or Moderate-Severe Hemophilia B. Blood, 2019. 134(Suppl. 1): p. 3348. One Year Data from a Phase 2b Trial of AMT-061 (AAV5-Padua hFIX variant), an Enhanced Vector for Gene Transfer in Adults with Severe or Moderate-Severe Hemophilia B | Blood | American Society of Hematology (ashpublications.org)
7. von Drygalski, A., et al., Stable and durable factor IX levels in hemophilia B patients over 3 years post etranacogene dezaparvovec gene therapy. Blood Adv, 2022. Stable and durable factor IX levels in hemophilia B patients over 3 years post etranacogene dezaparvovec gene therapy | Blood Advances | American Society of Hematology (ashpublications.org)

AAV, Adeno-associated virus; ABR, Annualized bleeding rate; AEs: adverse events; AIR, Annualized FVIII/FIX infusion rate; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CH, Chromogenic Assay; Co., cohort; DOACs, Direct oral anticoagulants; D, days; EDs, exposure days; FIX, factor IX; FIX-Padua, gain of function FIX variant; FVIII, factor VIII; gc, genome copies; HEK cells, human embryonic kidney cells; IQR, interquartile range; IRR, Infusion-related reaction; NAbs, neutralizing antibodies; OS, One-stage clotting assay; Pop., population; pt., patient/participant; pts., patients/participants; P1, Participant 1; PI, phase I; PBGD, porphobilinogen deaminase; PBMC, peripheral blood mononuclear cells; SAEs, serious adverse events; SFU, spot-forming units; TAC, tacrolimus; ULN, upper limit of normal; VCN, vector copy number; vg, vector genomes; W, weeks; WT, wild type; Y, year