ISTH - Recommended Resources

A compilation of Gene Therapy in Hemophilia scientific papers, selected clinical trials, regulatory documents and useful links

WFH eLearning Centre Resources

WFH Gene Therapy Registry – User guide for people with hemophilia
https://elearning.wfh.org

WFH Shared Decision Making Tool for Hemophilia Treatment
https://elearning.wfh.org

WFH eLearning Centre Clinical Trials
https://elearning.wfh.org

This eLearning Centre is published by the World Federation of Hemophilia
(WFH) and has been linked here with permission.

© 2022 World Federation of Hemophilia https://elearning.wfh.org/elearning/centres/clinical-trials

Scientific Papers and Regulatory Documents

Hemophilia Gene Therapy Reviews

1. Miesbach W, Klamroth R, Oldenburg J, Tiede A. Gene Therapy for Hemophilia-Opportunities and Risks. Dtsch Arztebl Int. 2022;119(51-52):887-894. doi:10.3238/arztebl.m2022.0353

2. Kaczmarek R, Herzog RW. Looking to the future of gene therapy for hemophilia A and B. Expert Rev Hematol. 2023;16(11):807-809. doi:10.1080/17474086.2023.2268279

3. Samelson-Jones BJ, George LA. Adeno-Associated Virus Gene Therapy for Hemophilia. Annu Rev Med. 2023;74:231-247. doi:10.1146/annurev-med-043021-033013

4. Abbasi J. Hemophilia gene therapies show promise. JAMA. 2018;319(6):539. https://www.ncbi.nlm.nih.gov/pubmed/29450507

5. Arruda VR, et al. Novel approaches to hemophilia therapy: successes and challenges. Blood. 2017;130:2251-2256. https://www.ncbi.nlm.nih.gov/pubmed/29018078

6. Balkaransingh P, et al. Novel therapies and current clinical progress in hemophilia A. Ther Adv Hematol.2018;9:49-61. https://www.ncbi.nlm.nih.gov/pubmed/?term=29387330

7. Beck DL. Breakthroughs in gene therapy for hemophilia. ASH Clinical News. Oct. 1, 2018. https://www.ashclinicalnews.org/features/breakthroughs-gene-therapy-hemophilia/

8. Colella P, et al. Emerging issues in AAV-mediated in vivo gene therapy. Mol Ther Meth Clin Dev. 2018;8:87-104. https://www.ncbi.nlm.nih.gov/pubmed/29326962

9. DiMichele DM. Navigating speed bumps on the innovation highway in hemophilia therapeutics. HemaSphere. 2018;2:e144. https://www.ncbi.nlm.nih.gov/pubmed/30887008

10. Doshi BS, et al. Gene therapy for hemophilia: what does the future hold? Ther Adv Hematol. 2018;9:273-293. https://www.ncbi.nlm.nih.gov/pubmed/30210756

11. Dunbar CE, et al. Gene therapy comes of age. Science. 2018;359:4672. https://www.ncbi.nlm.nih.gov/pubmed/29326244

12. Evens H, et al. Haemophilia gene therapy: From trailblazer to gamechanger. Haemophilia. 2018;24(Suppl. 6):50–59. https://www.ncbi.nlm.nih.gov/pubmed/29878653

13. George LA. Hemophilia gene therapy comes of age. Hematology Am Soc Hematol Educ Program. 2017;587-594. https://www.ncbi.nlm.nih.gov/pubmed/29222308

14. Mahlangu J, et al. Emerging therapies for haemophilia –Global perspective. Haemophilia. 2018;24(Suppl. 6):15–21. https://www.ncbi.nlm.nih.gov/pubmed/29878661

15. Makris M. A golden age for Haemophilia treatment? Haemophilia. 2018;24:175–176. https://www.ncbi.nlm.nih.gov/pubmed/29601683

16. Park CY, et al. Genome-editing technologies for gene correction of hemophilia. Human Genet. 2016;135:977-981. https://www.ncbi.nlm.nih.gov/pubmed/27357631

17. Perrin GQ, et al. Update on gene therapy for hemophilia. Blood. 2019;133:407-414. https://www.ncbi.nlm.nih.gov/pubmed/30559260

18. Pierce GF, et al. A cornucopia of therapies under study for hemophilia. Mol Ther. 2017;25:2429-2430. https://www.ncbi.nlm.nih.gov/pubmed/29055619

19. Pierce GF, et al. Past, present and future of haemophilia gene therapy: From vectors and transgenes to known and unknown outcomes. Haemophilia. 2018;24(Suppl. 6):60–67. https://www.ncbi.nlm.nih.gov/pubmed/29878660

20. Pierce GF, et al. The 1st WFH gene therapy round table: Understanding the landscape and challenges of gene therapy for haemophilia around the world. Haemophilia. 2019;1–6. https://www.ncbi.nlm.nih.gov/pubmed/30604914

21. Pipe SW. New therapies for hemophilia. Hematology Am Soc Hematol Educ Program. 2016;(1):650-656. https://www.ncbi.nlm.nih.gov/pubmed/27913542

22. Pipe SW. Gene therapy for hemophilia. Pediatr Blood Cancer. 2018;65:e26865. https://www.ncbi.nlm.nih.gov/pubmed/29077262

23. Schutgens R, et al. Gene therapy in hemophilia: From hype to hope. HemaSphere. 2018;2(2):22:e37. https://journals.lww.com/hemasphere/Fulltext/2018/04000

Recent Presentations

Risks and Benefits of Hemophilia Gene Therapy:
An EXPLORE™ Learning Experience
https://genetherapy.isth.org/education/explore-module

Useful Links

Shared Decision Making Tool
https://sdm.wfh.org

Genetic and Rare Diseases Information Center
https://rarediseases.info.nih.gov

Hemophilia and Gene Therapy (ASGCT)
https://www.youtube.com

National Bleeding Disorders Foundation (NBDF)
https://www.hemophilia.org/

World Federation of Hemophilia
https://www.wfh.org

Clinical Advances in Gene Therapy for Hemophilia
https://www.medscape.org

Selected Clinical Trials

Hemophilia A

  • NCT02576795. A Phase 1/2, Dose-Escalation, Safety, Tolerability and Efficacy Study of Valoctocogene Roxaparvovec, an Adenovirus-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Patients With Severe Haemophilia A. https://clinicaltrials.gov/ct2/show/NCT02576795
  • NCT03520712. A Phase 1/2 Safety, Tolerability, and Efficacy Study of Valoctocogene Roxaparvovec, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A Patients With Residual FVIII Levels ≤ 1 IU/dL and Pre-existing Antibodies Against AAV5. https://clinicaltrials.gov/ct2/show/NCT03520712
  • NCT03392974. Phase 3 Study to Evaluate Efficacy/Safety of Valoctocogene Roxaparvovec an AAV Vector-Mediated Gene Transfer of hFVIII at a Dose of 4E13vg/kg in Hemophilia A Patients With Residual FVIII Levels ≤1IU/dL Receiving Prophylactic FVIII Infusions. https://clinicaltrials.gov/ct2/show/NCT03392974
  • NCT03370913. A Phase 3 Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A Patients With Residual FVIII Levels ≤ 1 IU/dL Receiving Prophylactic FVIII Infusions. https://clinicaltrials.gov/ct2/show/NCT03370913
  • NCT03432520. A Multi-Center Evaluation of the Long-Term Safety and Efficacy of SPK-8011 [Adeno-Associated Viral Vector With B-Domain Deleted Human Factor VIII Gene] in Males With Hemophilia A. https://clinicaltrials.gov/ct2/show/NCT03432520
  • NCT03003533. Gene Transfer, Dose-Finding Safety, Tolerability, and Efficacy Study of SPK-8011 [a Recombinant Adeno-Associated Viral Vector With Human Factor VIII Gene] in Individuals With Hemophilia A. https://clinicaltrials.gov/ct2/show/NCT03003533
  • NCT03734588. Dose-finding Study of SPK-8016 Gene Therapy in Patients With Hemophilia A to Support Evaluation in Individuals With FVIII Inhibitors. https://clinicaltrials.gov/ct2/show/NCT03734588
  • NCT03370172. A Global, Open-Label, Multicenter, Phase 1/2 Study of the Safety and Dose Escalation of BAX 888, an Adeno-Associated Virus Serotype 8 (AAV8) Vector Expressing B-Domain Deleted Factor VIII (BDD-FVIII) in Severe Hemophilia A Subjects Administered a Single Intravenous Infusion. https://clinicaltrials.gov/ct2/show/NCT03370172
  • NCT03061201. A Phase 1/2, Open-Label, Adaptive, Dose-Ranging Study to Assess the Safety and Tolerability of SB-525 (Recombinant AAV2/6 Human Factor 8 Gene Therapy) in Adult Subjects With Severe Hemophilia A. https://clinicaltrials.gov/ct2/show/NCT03061201
  • NCT03001830. GO-8: Gene Therapy for Haemophilia A Using a Novel Serotype 8 Capsid Pseudotyped Adeno-associated Viral Vector Encoding Factor VIII-V3. https://clinicaltrials.gov/ct2/show/NCT03001830
  • NCT03217032. Lentiviral FVIII Gene Therapy for Hemophilia A. https://clinicaltrials.gov/ct2/show/NCT03217032
  • NCT03818763. Phase I Study Evaluating Safety and Feasibility of Hematopoietic Stem Cell Gene Transfer That Targets Factor VIII Delivery From Platelets for Patients With Hemophilia A. https://clinicaltrials.gov/ct2/show/NCT03818763

Hemophilia B

  • NCT02484092. Gene Therapy, Open-Label, Dose-Escalation Study of SPK-9001 [Adeno-Associated Viral Vector With Human Factor IX Gene] In Subjects With Hemophilia B. https://clinicaltrials.gov/ct2/show/NCT02484092
  • NCT03307980. FIX Long Study: A Factor IX(FIX) Gene Transfer, Multicenter Evaluation of the Long Term Safety and Efficacy Study of SPK9001 https://clinicaltrials.gov/ct2/show/NCT03307980
  • NCT02396342. A Phase I/II, Open-label, Uncontrolled, Single-dose, Dose-ascending, Multi-centre Trial Investigating an Adeno-associated Viral Vector Containing a Codon-optimized Human Factor IX Gene (AAV5-hFIX) Administered to Adult Patients With Severe or Moderately Severe Hemophilia B. https://clinicaltrials.gov/ct2/show/NCT02396342
  • NCT03569891. Phase III, Open-label, Single-dose, Multi-center, Multinational Trial Investigating a Serotype 5 Adeno-associated Viral Vector Containing the Padua Variant of a Codon-optimized Human Factor IX Gene (AAV5-hFIXco-Padua, AMT-061) Administered to Adult Subjects With Severe or Moderately Severe Hemophilia B. https://clinicaltrials.gov/ct2/show/NCT03569891
  • NCT03489291. Phase IIb, Open-label, Single-dose, Single-arm, Multi-center Trial to Confirm the Factor IX Activity Level of the Serotype 5 Adeno-associated Viral Vector Containing the Padua Variant of a Codon-optimized Human Factor IX Gene (AAV5-hFIXco-Padua, AMT-061) Administered to Adult Subjects With Severe or Moderately Severe Hemophilia B. https://clinicaltrials.gov/ct2/show/NCT03489291
  • NCT01687608. A Phase 1/2 Open-Label, Single Ascending Dose Trial of a Self-Complementing Optimized Adeno-associated Virus Serotype 8 Factor IX Gene Therapy (AskBio009) in Adults With Hemophilia B. https://clinicaltrials.gov/ct2/show/NCT01687608
  • NCT03369444. A Phase I/II, Open Label, Multicentre, Ascending Single Dose, Safety Study of a Novel Adeno- Associated Viral Vector (FLT180a) in Patients With Haemophilia B. https://clinicaltrials.gov/ct2/show/NCT03369444
  • NCT03641703. An Open-Label, Multicentre, Long-Term Follow-Up Study to Investigate the Safety and Durability of Response Following Dosing of a Novel Adeno-Associated Viral Vector (FLT180a) in Patients With Haemophilia B. https://clinicaltrials.gov/ct2/show/NCT03641703
  • NCT02695160. A Phase I, Open-Label, Ascending Dose Study to Assess the Safety and Tolerability of AAV2/6 Factor IX Gene Therapy Via Zinc Finger Nuclease (ZFN) Mediated Targeted Integration of SB-FIX in Adult Subjects With Severe Hemophilia B. https://clinicaltrials.gov/ct2/show/NCT02695160
  • NCT00979238. An Open Label Dose-Escalation Study Of A Self Complementary Adeno-Associated Viral Vector (scAAV 2/8-LP1-hFIXco) For Gene Transfer in Hemophilia B. https://clinicaltrials.gov/ct2/show/NCT00979238
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