Gene therapy for hemophilia: a review on clinical benefit, limitations, and remaining issues

Frank W.G. Leebeek*, Wolfgang Miesbach

*Corresponding author for this work

Research output: Contribution to journalReview articleProfessionalpeer-review

71 Citations (Scopus)


In the last decade, enormous progress has been made in the development of gene therapy for hemophilia A and B. After the first encouraging results of intravenously administered adeno-associated virus (AAV)-based liver-directed gene therapy in patients with severe hemophilia B were reported in 2011, many gene therapy studies have been initiated. Most of these studies, using AAV vectors with various gene constructs, showed sufficient factor VIII and IX expression in patients to significantly reduce the number of bleeds and the need for prophylaxis in most patients with severe hemophilia. This resulted in great clinical benefit for nearly all patients. In this review, we will summarize the most recent findings of reported and ongoing gene therapy trials. We will highlight the successful outcome of trials with focus on the results of recently reported phase 1 trials and preliminary results of phase 2b/3 trials for hemophilia A and B. These new reports also reveal the impact of side effects and drawbacks associated with gene therapy. We will therefore also discuss the limitations and remaining issues of the current gene therapy approaches. These issues must be resolved before gene therapy will be widely available for the hemophilia patient population.

Original languageEnglish
Pages (from-to)923-931
Number of pages9
Issue number11
Publication statusPublished - 16 Sept 2021

Bibliographical note

Funding Information:
Conflict-of-interest disclosure: F.W.G.L. received unrestricted research grants from CSL Behring, Shire/Takeda, and uniQure; is a consultant for CSL Behring, Shire/Takeda, Biomarin, and uniQure, of which the fees go to the University; has received travel support from SOBI; and is a Data Safety Monitoring Board member of a study sponsored by Roche. W.M. received unrestricted research grants from Amgen, Bayer, Biotest, CSL, LFB, Novo Nordisk, Octapharma, Pfizer, Shire, and Sobi; is a consultant for Ablynx, Amgen, Aventis, Bayer, Biomarin, Freeline, Leo, LFB, Octapharma, Sobi, Novartis, Novo Nordisk, Octapharma, Pfizer, Roche, Sanofi, Sobi, and UniQure; and is a DSMB member of a study sponsored by Octapharma.

Publisher Copyright:
© 2021 American Society of Hematology


Dive into the research topics of 'Gene therapy for hemophilia: a review on clinical benefit, limitations, and remaining issues'. Together they form a unique fingerprint.

Cite this