Evolution of AAV Vector Gene Therapy Is Ongoing in Hemophilia. Will the Unique Features of BAY 2599023 Address the Outstanding Needs?

Highlights From the ISTH 2021 Congress

Evolution of AAV Vector Gene Therapy Is Ongoing in Hemophilia. Will the Unique Features of BAY 2599023 Address the Outstanding Needs?

S.W. Pipe¹, C. Hay², J. Sheehan³, T. Lissitchkov⁴, M. Coppens⁵, H. Eichler⁶, S. Weigmann⁷, F. Ferrante⁸

¹University of Michigan, Ann Arbor, United States

²Manchester University Dept. of Haematology, Manchester, United Kingdom

³University of Wisconsin–Madison, Madison, United States

⁴National Specialized Hospital for Active Treatment of Haematologic Diseases, Sofia, Bulgaria

⁵Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands

⁶Institute of Clinical Haemostaseology and Transfusion Medicine, Saarland University, Homburg, Germany

⁷Bayer, Wuppertal, Germany

⁸Bayer, Basel, Switzerland

Key Data Points

Phase 1/2 Study Design
Factor FVIII Expression Following Infusion of BAY2599023

Inclusion criteria, cohort dosing, and study endpoints for the ongoing phase 1/2 BAY2599023 dose-finding study. Males with severe hemophilia A, no known FVIII inhibitor history, an AAVhu37 neutralizing antibody titer ≤ 5, and > 150 exposure days to FVIII products were enrolled sequentially into three dose cohorts to receive a single intravenous infusion of BAY2599023, with at least two patients per dose level (patients to be enrolled in Cohort 4 will receive 4 × 10¹³ gene copies/kg).

Factor FVIII Expression Following Infusion of BAY2599023

FVIII expression levels following transgene infusion with the first 3 doses in a total of 8 patients. At the data cut off, May 21, 2021, chromogenic B-domain-deleted FVIII levels were available for a period ranging from 12 weeks for Patient 8 to 100 weeks for Patient 2. A dose response was observed from cohort 1 to cohort 3, with sustained FVIII levels achieved over a time of up to > 23 months. None of the patients reported spontaneous bleeds or other bleeds requiring treatment, once protective FVIII levels of > 11 IU/dL were achieved.