Uniqure N.v. · NASDAQ:QURE
Uniqure — Technical Presentation (June 2021)
13 slides from Uniqure's technical presentation, Jun 18, 2021
Slide 1: Clinical Outcomes in Adults with Hemophilia B With and Without Pre-existing Neutralizing Antibodies to AAV5
Clinical Outcomes in Adults with Hemophilia B With and Without Pre-existing Neutralizing Antibodies to AAV5: 6 Month Data from the Phase 3 Etranacogene Dezaparvovec HOPE-B Gene Therapy Trial Frank W.G. Leebeek1, Wolfgang Miesbach2, Michael Recht3, Nigel S. Key4, Susan Lattimore3, Giancarlo Castaman5
Slide 2: Disclosures for Frank W.G. Leebeek
Disclosures for Frank W.G. Leebeek In compliance with COI policy, ISTH requires the following disclosures to the session audience: Research Support/P.I. Unrestricted research grants from CSL Behring, Takeda, Sobi, UniQure Employee No relevant conflicts of interest to declare Consultant CSL Behring,
Slide 3: HOPE-B: Etranacogene dezaparvovec (AAV5-Padua hFIX)
HOPE-B: Etranacogene dezaparvovec (AAV5-Padua hFIX) ▪ Ongoing Phase 3 study in hemophilia B Etranacogene dezaparvovec: ▪ N=54 Hyperactive FIX Padua variant ▪ Mean FIX activity increased to near-normal levels at 6 months post-etranacogene dezaparvovec, meeting the first co-primary AAV5 endpoint1 ▪ An
Slide 4: Rationale for not excluding pre-existing anti-AAV5 NAbs
Rationale for not excluding pre-existing anti-AAV5 NAbs ▪ Pre-existing NAbs resulting from previous exposure to AAV may prevent efficient transduction of the therapeutic transgene due to the host’s immune response against the vector 1 ▪ However, prior clinical data have not shown pre-existing anti-A
Slide 5: HOPE-B (AMT-061): study design
HOPE-B (AMT-061): study design1 Screening visit Key inclusion criteria ~ 4 wks ▪ Male adults ≥18 years Visits every 2 months, ▪ FIX activity ≤2% of normal Lead-in phase phone calls on alternating ▪ Continuous prophylaxis for ≥2 months (26 weeks) months ~ 4 wks Key exclusion criteria Single dose of A
Slide 6: HOPE-B: study endpoints and analyses
HOPE-B: study endpoints and analyses1 ▪ Primary endpoints ▪ FIX activity (central one stage aPTT) at 26 weeks after dosing1 ▪ FIX activity 52 weeks after dosing* ▪ 52-week ABR compared to lead-in* ▪ Secondary endpoints ▪ Rates of total, spontaneous, traumatic, and treated/untreated bleeds ▪ FIX cons
Slide 7: HOPE-B: Patient disposition
HOPE-B: Patient disposition1 ▪ 54 patients were dosed and completed 26-weeks of follow up 75 patients screened 8 screen failures 67 entered lead-in phase 13 patients discontinued 54 patients dosed prior to dosing (FAS population)b,c Ineligible fibroscana score, concomitant medication, co-morbidities
Slide 8: HOPE-B: Baseline demographics
HOPE-B: Baseline demographics Full analysis set antiAAV5 NAb +ve antiAAV5 NAb –ve (n=54) (n=23) (n=31) Age, mean (SD, min-max), years 41.5 (15.8, 19-75) 43.1 (17.4, 19-75) 40.3 (14.6, 21-73) Severity of hemophilia B at time of diagnosis, n (%) Severe (FIX <1%) 44 (81.5) 17 (73.9) 27 (87.1) Moderatel
Slide 9: FIX activity by baseline NAb status
HOPE-B: FIX activity by BL NAb status: Up to 26 weeks ▪ Mean FIX activity at 26 weeks was 41.3 IU/dL in participants without NAbs and 32.7 IU/dL in those with NAbs Q1-Q3 Median Mean Min/max 100 100 NAb + (n=23) NAb – (n=31) FIX activity, central one-stage (IU/dL) 90 90 80 80 70 70 60 60 50 50 40 40
Slide 10: Pre-existing NAb titers vs FIX activity
HOPE-B: Pre-existing NAb titers vs week 26 FIX activity ▪ No clinically significant correlation of pre-existing NABs with FIX activity identified up to a titer of 678 ▪ One patient with a titer of 3212.3 did not respond (data not shown) 100 Pearson product-moment correlation (95% CI): -0.28 (-0.51,
Slide 11: Post-treatment bleeds by NAb baseline
HOPE-B: Post-treatment bleeds by NAb baseline Baseline ▪ For subjects with bleeds, no clinically significant difference in individual patterns of post-treatment bleeds NAb titer in subjects with and without baseline NAbs 15 3212.3 NAb + Type Treated Patients with NAbs 14 449.9 13 111.5 4 Spontaneous
Slide 12: Most common treatment-related AEs
HOPE-B: Most common treatment-related AEs AE, preferred term Participants with NAbs Participants without NAbs N = 23 N = 31 n (%) n (%) Transient transaminitis, requiring 2 (8.7) 7 (22.6) corticosteroids Infusion-related reactions 5 (21.7) 2 (6.5) Headache 2 (8.7) 5 (16.1) Influenza-like illness 4 (
Slide 13: Conclusions
HOPE-B: Conclusions ▪ FIX activity was similar in participants without and with pre-existing NAbs to AAV5 up to a titer of 678 ▪ No relationship between AAV5 NAbs and safety was observed ▪ This study demonstrates for the first time, successful treatment of patients with pre-existing NAbs at generall