What is the efficacy of gene therapy for hemophilia A?

Updated: Jan 14, 2019
  • Author: Douglass A Drelich, MD; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
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Preclinical studies in mice and dogs with hemophilia have resulted in long-term correction of the bleeding disorders and, in some cases, a permanent cure. Preliminary results in human trials of gene therapy for hemophilia B have yielded encouraging results, but hemophilia A has proved more problematic, given the much larger size of FVIII DNA and the frequent development of neutralizing antibodies. [59] Implantation of liver-derived stem cells that have been expanded in vitro is under consideration, as these could theoretically induce a steady-state production of quantities of factor sufficient to prevent spontaneous bleeding. [60]

In December 2017, Rangarajan et al reported sustained rises in FVIII levels and declines in bleeding rates in patients with severe hemophilia A who received gene therapy with a single intravenous dose of valoctocogene roxaparvovec, a codon-optimized adeno-associated virus serotype 5 (AAV5) vector encoding a B-domain–deleted human FVIII. In the seven participants who received a high dose of of valoctocogene roxaparvovec, FVIII activity levels remained in the normal range 1.5 years after gene transfer, and their annualized bleeding rate dropped from 16.5 to 0. All participants were able to completely discontinue prophylactic FVIII infusions, and none developed FVIII inhibitors. [61, 62]

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