Recommended Resources

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

Scientific Papers and Regulatory Documents

Hemophilia Gene Therapy Reviews

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

2. 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

3. 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

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

5. 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

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

7. 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

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

9. 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

10. 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

11. 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

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

13. 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

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

15. 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

16. 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

17. 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

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

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

20. 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

Useful Links

National Hemophilia Foundation
https://www.hemophilia.org/

World Federation of Hemophilia
https://www.wfh.org/en/page.aspx?pid=492

Clinical Advances in Gene Therapy for Hemophilia
https://www.medscape.org/sites/advances/gene-therapy-hemophilia

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