An Interesting Paper on Hemophilia Therapy

The past decade has seen some major changes in hemophilia therapy with the development of various modified factor VIII therapeutic products and scientific advances such as CRISPR/Cas 9 and TALENS which have promise for gene therapy.  Gene therapy has the potential of providing long term prophylaxis solving the need for frequent product injection and there are several longer-acting factor VIII concentrates which decrease the frequency of injections required to maintain effective hemostasis.  As personal note, the hemophilia biz has gotten quite crowded since I met factor VIII in Seattle years ago.  I would also caution that hemophilia does not always mean factor V III deficiency but also can include factor IX deficiency and other deficiencies.
In the midst the excitement about new therapeutic approaches to hemophilia A, I was very pleased to see a thoughtful paper by Paul Giangrande entitled “The Future of Hemophilia Treatment: Longer-Acting Factor Concentrates versus Gene Therapy (Seminars in Thrombosis and Hemostasis 42, 513-517, 2016).   Dr. Giangrande discusses the new therapeutic options and includes other issues such the lowest level of factor providing hemostasis and the availability of previously treated patients (PUPS) for the necessary clinical trials of new therapeutics.   In my opinion, his more thoughtful comments concerned product pricing as there may be difficulty in obtaining premium pricing for the new longer-acting products and the very high cost anticipated for gene therapy may pose a significant hurdle.  I would note that there has been considerable discussion of drug prices in the United States.  There is a trend by third-party payers where the high price of a therapeutic may well require a guarantee for product performance.   Drug delivery may also be an issue for gene therapy since the AAV “payload” may not be sufficient for CRISPR/Cas although protein engineering has the promise to lower the size of the protein.   Dr. Giangrande does mention the potential of using stem cells for product delivery. To add to the mix, there are some efforts at developing factor VIII mimetics which I have previously discussed on this site.  Finally, I would be negligent if I did not mention that other workers (1-6) have also considered these issues.


1.  Carcao, M.D., and Iorio, A., Individualizing factor replacement in severe hemophilia, Semin.THromb.Hemost,  41, 563-576, 2015
2.  Coppola, A., Marrone, E., Conca, P., et al.,  Safety of switching factor VIII products in the era of evolving concentrates: Myths and facts, Semin.Thromb.Hemost. 42, 563-575, 2016
3.  Ward, P. and Walsh, C.E., Current and future prospects for hemophilia gene therapy, Expert Rev.Hematol. 9, 649-659, 2016
4.   Park, C.Y., Lee, D.R., Sung, J.J., and Kim, D.W., Genome-editing technologies for gene correction of hemophilia, Hum.Genet. 135, 977-981, 2016
5.  Crivanu-Gaita, V., Rivard, G.E., Carao, M., et al., Pilot study of once-a-day prophylaxis for youth and young adults with severe hemophilia A, Haemophilia 22:e401-e405, 2016
6.  Berntorp, E., Hart, D., Mancuso, M.E., et al., The first Team Haemophilia Education meeting , 2015, Amsterdam, The Netherlands, Eur.J.Haematol. 97(Suppl 83), 3-18, 2016