Safety and Efficacy of Turoctocog Alfa in the Prevention and Treatment of Bleeding Episodes in Previously Treated Patients from China with Severe Hemophilia A: Results from the Guardian 7 Trial

Abstract

Purpose

Hemophilia care in China is characterized by widespread use of on-demand regimens and low-dose prophylaxis. With a limited number of approved recombinant factor VIII (FVIII) products, the incidence of arthropathy and disability in hemophilia patients remains high in China. The purpose of this trial was to evaluate the safety and efficacy of turoctocog alfa for prophylaxis and treatment of bleeding episodes in patients from China with severe hemophilia A across all age groups.

Patients and Methods

In this Phase 3, open-label trial, previously treated males of all ages with severe hemophilia A from China received turoctocog alfa for prophylaxis or on-demand treatment of bleeds. The primary endpoint was hemostatic effect for the treatment of bleeds during the main phase of the trial. Secondary endpoints included annualized bleeding rate during prophylaxis and the frequency of FVIII inhibitor development.

Results

Overall, 42 pediatric patients (age <12 years) and 26 adolescent/adult patients (≥12 years) were dosed with turoctocog alfa; 51 patients initiated treatment with prophylaxis, while 17 patients initiated on-demand treatment. During the main phase of the trial (6 months), hemostatic success was 95.1%. During the full trial (up to 24 months), hemostatic success was 95.4%; the overall median ABR was 1.18 bleeds/patient/year for prophylaxis patients; and 25 (51.0%) of 49 patients with target joints at baseline had all target joints resolved. No FVIII inhibitors (≥0.6 BU) were reported.

Conclusion

Turoctocog alfa was safe and effective for prophylaxis and treatment of bleeding episodes and for surgery in patients from China with severe hemophilia A across all ages.

Keywords:

• hemophilia A
• prophylaxis
• recombinant factor VIII
• turoctocog alfa
• China

Data Sharing Statement

Data sets from Novo Nordisk-sponsored clinical research completed after 2001 for product indications approved in both the EU and US will be shared with bona fide researchers submitting a research proposal requesting access to data. The access request proposal form and the access criteria can be found at novonordisk-trials.com. Data will be available permanently after research completion and approval of product and product use in both the EU and US on a specialised Statistical Analysis System data platform. The analyses available for use will be those as approved by the Independent Review Board according to the IRB Charter (see novonordisk-trials.com). Individual participant data will be shared in data sets in a de-identified/-anonymised format. In addition, the study protocol and redacted Clinical Study Report will be available according to Novo Nordisk data sharing commitments.

Acknowledgments

The trial was sponsored by Novo Nordisk A/S (Bagsværd, Denmark). The authors thank all the participants, their families, investigators and trial staff who were involved in the trial. We also thank Lars Korsholm and Kerstin Pietzko (previously at Novo Nordisk) for their review and input to the manuscript, and James McCary, BSc (AXON Communications, London, UK) for medical writing and editorial support in preparation of the manuscript.

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

RW has received consulting fees from Novo Nordisk, is a steering committee member for Bayer, and is a member of the speakers’ bureaus for Novo Nordisk. IM is an employee of Novo Nordisk A/S. SZ is an employee of Novo Nordisk (China) Pharmaceuticals Co., Ltd. MP is a paid consultant to and reports personal fees from Novo Nordisk A/S. RY has received speaker/consultancy fees from Bayer, Novo Nordisk, Pfizer, Roche and Takeda, outside the submitted work. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study and editorial support for the article were funded by Novo Nordisk A/S, Denmark.