Stable Elevations in FIX Activity and Reductions in Annualized Bleeding Rate over up to 2 Years of Follow-up of Adults with Severe or Moderate-Severe Hemophilia B Treated with AMT-060 (AAV5-hFIX) Gene Therapy

Background: Gene transfer for hemophilia offers the potential to convert the disease from a severe to mild phenotype with a single treatment. AMT-060 consists of an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized wildtype human factor IX (FIX) gene under control of a liver-specific promoter. Aim: This phase 1/2 study investigates the safety and efficacy of AMT-060 at 2 dose levels in adults with moderate-severe or severe hemophilia B. Updated data with up to 2 years follow up will be presented. Methods: Multi-national, open-label, dose-escalating study in patients (pts) with FIX activity ≤2 IU/dL of normal, and a severe bleeding phenotype (prophylactic exogenous FIX; or on-demand exogenous FIX, plus ≥4 bleeds/year or hemophilic arthropathy). Pts received either 5x10 12 gc/kg (Cohort 1, n=5) or 2×10 13 gc/kg (Cohort 2, n=5) of AMT-060 iv. Efficacy assessments include FIX activity (measured ≥10 days after use of exogenous FIX); reduction of FIX use; and annualized spontaneous bleeding rates. Safety assessments include treatment related adverse events, immunological and inflammatory biomarkers. Results: Nine pts with severe (FIX Conclusions: Longer-term outcomes for up to 1.5 years following a single infusion of AMT-060 continue to indicate a positive safety profile coupled with stable and clinically meaningful elevations in FIX protein expression and activity without evidence of capsid-specific immune responses. Bleeding rates declined over time, with a near cessation of spontaneous bleeds in the high dose cohort. Disclosures Meijer: BMS: Consultancy; Boehringer Ingelheim: Consultancy; Sanquin: Consultancy; Bayer: Consultancy; Uniqure BV: Consultancy; Aspen: Consultancy. Coppens: Bayer: Consultancy; CSL Behring: Consultancy; Uniqure BV: Consultancy. Kampmann: Uniqure BV: Research Funding. Klamroth: Shire: Consultancy; Biotest: Consultancy; SOBI: Consultancy; Pfizer: Consultancy; CSL Behring: Consultancy; Bayer: Consultancy; Chiesi: Consultancy; Octapharma: Consultancy; Novo Nordisk: Consultancy. Schutgens: Uniqure BV: Research Funding; CSL Behring: Research Funding; Pfizer: Research Funding; Novo Nordisk: Research Funding; Bayer: Research Funding; Baxalta/Shire: Research Funding. Castaman: Pfizer: Membership on an entity9s Board of Directors or advisory committees, Research Funding; CSL Behring: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Sobi: Membership on an entity9s Board of Directors or advisory committees; Kedrion: Membership on an entity9s Board of Directors or advisory committees; Shire: Membership on an entity9s Board of Directors or advisory committees; Novo Nordisk: Membership on an entity9s Board of Directors or advisory committees. Sawyer: Uniqure BV: Employment.