Lynn Malec1,a, Manuel Carcao2, Nisha Jain3, Mariya Spasova4, Dobrin Konstantinov5, Neha Bhatnagar6, Anjali Sharathkumar7, Nidra Rodriguez8, Nina Hwang9, Anthony Chan10, Michael Wang11, An Van Damme12, Jordan Wright13, Saturnino Haya14, Elisa Tsao3, Caroline Reuter3, Stefan Lethagen15,16, Flora Peyvandi17

1Versiti Blood Research Institute, Milwaukee, WI, USA; 2The Hospital for Sick Children, Toronto, ON, Canada; 3Sanofi, Waltham, MA, USA; 4University Multiprofile Hospital for Active Treatment “Sveti Georgi,” Plovdiv, Bulgaria; 5University Multiprofile Hospital for Active Treatment “Tsaritsa Yoanna–ISUL,” Sofia, Bulgaria; 6Oxford Haemophilia and Thrombosis Centre, Children’s Hospital Oxford, John Radcliffe Hospital, Oxford, UK; 7University of Iowa Stead Family Children’s Hospital, Iowa City, IA, USA; 8The University of Texas Health Science Center, Houston, TX, USA; 9Center for Inherited Blood Disorders, Orange, CA, USA; 10McMaster Children’s Hospital/Hamilton Health Sciences Foundation, Hamilton, ON, Canada; 11University of Colorado Hemophilia and Thrombosis Center, Aurora, CO, USA; 12Saint-Luc University Hospital, Université Catholique de Louvain, Brussels, Belgium; 13Dayton Children’s Hospital, Dayton, OH, USA; 14Hospital Universitari i Politècnic La Fe, Valencia, Spain; 15Sobi, Stockholm, Sweden; 16Copenhagen University, Copenhagen, Denmark; 17Università Degli Studi Di Milano, Milan, Italy
aPresenting author

Background

  • Development of inhibitors to factor VIII (FVIII) treatment remains a major challenge in the treatment of haemophilia A1
  • Immune tolerance induction (ITI) therapy is the standard of care for inhibitor eradication2
  • ITI success rates of 50%–80% are reported2–4
  • Recombinant FVIII Fc fusion protein (rFVIIIFc) is the first extended half-life product with data available for ITI5

Materials and Methods

  • verITI-8 (NCT03093480) is a prospective, open-label, Phase 4 study of rFVIIIFc for first-time ITI
  • Target including 30 subjects with severe haemophilia A and high-titre inhibitors (historical peak ≥5 Bethesda units [BU]/mL)
  • Primary endpoint is time to tolerisation (i.e., ITI success), defined as meeting all of the following:
    • Negative inhibitor titre (<0.6 BU/mL by Nijmegen-modified Bethesda assay) at two consecutive visits (testing conducted at Weeks 2, 4 and every 4 weeks thereafter)
    • Incremental recovery ≥66% (≥1.32 IU/dL per IU/kg) at two consecutive visits
    • rFVIIIFc half-life ≥7 hours
  • Secondary endpoints include the number of subjects with ITI success and adverse events (AE)
  • Interim analysis was planned for when 10 subjects received at least 6 months of ITI
    • Interim analysis data cut: 23 January 2019

Results

  • Median (interquartile range) time to tolerisation for the 6 subjects who reached ITI success is 11.7 (9.9–12.3) weeks (Table 2)
  • No AEs or serious AEs were assessed as related to rFVIIIFc by local investigators (Table 3)

Summary

  • Results are based on an interim data cut; study is ongoing with 8 subjects in ITI
  • rFVIIIFc was generally well tolerated for ITI therapy

Conclusions

  • Early results from this prospective study of first-time ITI indicate that rFVIIIFc may offer rapid time to tolerisation in some subjects with severe haemophilia A who have historical high-titre inhibitors

REFERENCES

  1. Pasi KJ, et al. N Engl J Med. 2017;377:819-828.
  2. DiMichele DM, et al. Haemophilia. 2007;13(Suppl 1):1-22.
  3. Wight J, et al. Haemophilia. 2003;9:436-463.
  4. Oldenburg J, et al. Haemophilia. 2014;20(1):83-91.
  5. Carcao M, et al. Haemophilia. 2018:24(2):245-252.

DISCLOSURES

This study was funded by Sanofi and Sobi. Data first presented at the 27th Congress of the International Society on Thrombosis and Haemostasis (ISTH), July 6–10, 2019, Melbourne, Australia. Sanofi and Sobi reviewed and provided feedback on the poster. The authors had full editorial control of the poster, and provided their final approval of all content.

MS, DK, NB and NR have nothing to disclose. LM has presented in advisory boards, and/or received consultancy fees or investigator-initiated grant funding from Bioverativ, a Sanofi company, Shire and/or Bayer. MC has received research support and/or honoraria for speaking/participating in advisory boards from Bayer, Bioverativ, CSL Behring, Grifols, LFB, Novo Nordisk, Octapharma, Pfizer, Roche and/or Shire. NJ, ET and CR are employees of Sanofi. AS received honorarium for advisory boards from Bayer, CSL Behring, Kedrion, Pfizer and Shire. NH has served as a consultant for Bayer, BPI, HEMA Biologics and Shire, and as a clinical research principle investigator for Bioverativ. AC has participated in an advisory board for Bioverativ. MW has received research funding and/or honoraria from Bioverativ, Novo Nordisk, Octapharma, Shire, Genentech, HEMA Biologics, Bayer, BioMarin and/or Pfizer. AVD has received personal fees from Bayer, Pfizer and Shire outside the submitted work. JW has received non-financial support and other from Bioverativ during the conduct of this study, and non-financial support and other from Novo Nordisk outside the submitted work. SH has given lectures at educational symposiums and/or advisory boards organized by Baxter, Grifols, Novo Nordisk and/or Pfizer. SL is an employee of Sobi. FP has received personal fees from Ablynx, Grifols, Kedrion, Novo Nordisk, Roche, Shire and Sobi outside the submitted work.

AKNOWLEDGEMENTS

Editorial assistance for the development of this poster was provided by JK Associates Inc., a member of the Fishawack Group of Companies, and was funded by Sanofi.

Joint 10th BIC International Conference and 3rd International Conference on Inhibitors in Hemophilia, September 6–8, 2019, Venezia, Italy