Real-world long-term safety and effectiveness of turoctocog alfa in the treatment of haemophilia A in Japan: results from a multicentre, non-interventional, post-marketing study

ABSTRACT

Objectives

To assess the safety and effectiveness of turoctocog alfa in previously treated patients (PTPs) and previously untreated patients (PUPs) with haemophilia A in a real-world setting in Japan.

Methods

This multicentre, non-interventional, post-marketing study recruited patients with haemophilia A who initiated treatment with turoctocog alfa from 18 sites (08/2014-12/2018). The primary endpoint was adverse events (AEs) during the 2-year study period.

Results

The safety and effectiveness analysis set included 39 patients. In total, 13 (33.3%) patients reported ≥1 AE; incidence rate was 60.4 events/100 patient-years of exposure (PYE). Treatment was withdrawn in two cases: pruritus in a PTP and factor VIII inhibitor development in a PUP. Inhibitor development occurred in 2.6% of all patients, with an incidence rate of 3.8 events/100 PYE. The rate of inhibitor development was 0%, 25% and 20% in PTPs, PUPs and PUPs with severe type, respectively. The haemostatic success rate was 91.4% for 383 bleeding episodes and 85.7% for 14 surgeries. The negative binomial annualised bleeding rate for the prophylaxis regimen was 6.19 episodes/year (95% CI, 3.69–10.38). The mean (SD) total consumption of turoctocog alfa (n = 34; excluding FVIII inhibitors) was 5,382.6 (7,180.1) IU/kg/year/patient; consumption was 4,133.1 (1,452.4) IU/kg/year/patient for prophylaxis.

Discussion

The effectiveness and safety profiles were comparable to those observed in other turoctocog alfa trials; effectiveness analysis and consumption were not affected by treatment regimens.

Conclusion

Long-term use of turoctocog alfa therapy in clinical practice posed no newly identified safety issues and was effective for prophylaxis and treatment of bleeds in patients with haemophilia A in Japan.

KEYWORDS:

• Factor VIII
• Haemophilia A
• Japan
• inhibitors
• prophylaxis
• post-marketing product surveillance
• turoctocog alfa

Acknowledgements

We would like to thank all the investigators and patients who participated in the study. Medical writing support was provided by Khi Khi Choo, PhD, of Cactus Life Sciences (part of Cactus Communications) and funded by Novo Nordisk Pharma Ltd., Japan. We would also like to acknowledge Masaki Endo (Novo Nordisk Pharma Ltd.) for his contribution.

Disclosure statement

Azusa Nagao received investigator-initiated grant funding from Takeda (Shire) and Bayer and honoraria from Sanofi, Takeda, Chugai, Bayer, Fujimoto, KMB, Pfizer, JB, Novo Nordisk and CSL, outside the submitted work. Ayumi Deguchi is an employee of Novo Nordisk Pharma Ltd. Keiji Nogami received grants from Takeda Co. Ltd., Sanofi S.A. and CSL Behring; research funding from Chugai Pharmaceutical Co., Ltd., F. Hoffmann-La Roche Ltd., Bayer A/G, Novo Nordisk A/S and KM Biologics; and honoraria from Takeda Co. Ltd. (Baxalta/Shire), Bayer A/G, Novo Nordisk A/S, Sanofi S.A. (Biogen/Bioverativ), CSL Behring, Chugai Pharmaceutical Co., Ltd., F. Hoffmann-La Roche Ltd., KM Biologics (Kaketsuken) and Fujimoto Seiyaku, outside the submitted work.

Data availability 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 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 approved by an 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 the Novo Nordisk data-sharing commitments.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This study and the editorial support for this article were funded by Novo Nordisk Pharma Ltd.