Damoctocog Alfa Pegol: A Review in Haemophilia A
Damoctocog alfa pegol (Jivi®) is approved in the USA, EU, Japan and Canada for the treatment and prophylaxis of previously treated patients aged ≥ 12 years with haemophilia A. Formulated with a 60 kDa polyethylene glycol (PEG) moiety, damoctocog alfa pegol is an intravenously (IV) administered recombinant factor VIII (rFVIII) product with a longer terminal half-life than non-PEGylated FVIII and rFVIII products. In the multinational phase II/III PROTECT VIII trial, prophylaxis with damoctocog alfa pegol reduced the likelihood of bleeding in previously treated patients aged ≥ 12 years with severe haemophilia A, with dosing schedules ranging from twice weekly to once every 7 days. Interim data from the ongoing extension phase indicated that the reduced annualized bleeding rates (ABRs) were maintained for up to 5.2 years of prophylaxis with damoctocog alfa pegol. Damoctocog alfa pegol was also effective in treating bleeding episodes and in providing haemostatic control during surgery. Damoctocog alfa pegol was generally well tolerated in adult and adolescent patients with severe haemophilia A, with most adverse events considered to be unrelated to treatment. There were no new or confirmed cases of FVIII inhibitor development and anti-PEG antibodies, observed in some patients, were of low titre and transient. Damoctocog alfa pegol extends the available treatment options in previously treated adults and adolescents with haemophilia A, offering the possibility of up to once-weekly administration for suitable patients.
During the peer review process, the manufacturer of damoctocog alfa pegol was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.
Compliance with Ethical Standards
The preparation of this review was not supported by any external funding.
Conflicts of interest
Julia Paik and Emma Deeks are salaried employees of Adis International Ltd/Springer Nature, are responsible for the article content and declare no relevant conflicts of interest.
- 13.US Food and Drug Administration. JIVI (antihemophilic factor (recombinant), PEGylated-aucl): clinical review. 2018. https://www.fda.gov/. Accessed 6 June 2019.
- 14.European Medicines Agency. Damoctocog alfa pegol (Jivi): EU summary of product characteristics. 2018. http://www.ema.europa.eu. Accessed 6 June 2019.
- 15.Pharmaceuticals and Medical Devices Agency. Jivi® for IV injection: Japanese prescribing information. 2018. http://www.pmda.go.jp/. Accessed 6 June 2019.
- 16.Bayer HealthCare LLC. JIVI® [antihemophilic factor (recombinant), B-domain deleted, PEGylated]: Canadian product monograph. 2018. https://www.bayer.ca/. Accessed 6 June 2019.
- 17.Bayer HealthCare LLC. JIVI® [antihemophilic factor (recombinant), PEGylated-aucl]: US prescribing information. 2018. https://www.fda.gov/. Accessed 6 June 2019.
- 23.Yada K, Nogami K, Patel C, et al. A factor VIII with site-specific PEGylation attenuates the binding with inhibitors results in the retention of hemostatic effect [abstract]. Blood. 2015;126(23):1076.Google Scholar
- 24.Maas Enriquez M, Katterle Y, Baumann A, et al. BAY 94-9027 PROTECT VIII studies: observation of pharmacokinetic steady state for 60-kDa PEG demonstrates the existence of elimination processes for PEG [abstract no. T-FPMED02-002 (600)]. Haemophilia. 2018;24(Suppl 5):16.Google Scholar
- 27.Shah A, Coyle T, Lalezari S, et al. BAY 94-9027, a PEGylated recombinant factor VIII, exhibits a prolonged half-life and higher area under the curve in patients with severe haemophilia A: comprehensive pharmacokinetic assessment from clinical studies. Haemophilia. 2018;24(5):733–40.CrossRefGoogle Scholar
- 28.Ahsman M, Vis P, Shah A, et al. Predictable and reliable individualized pharmacokinetic profiling with BAY 94-9027: integrated population pharmacokinetics analysis [abstract no. T-P-092 (372)]. Haemophilia. 2018;24(Suppl 5):89–90.Google Scholar
- 29.Thomson G, Holme PA, Wang M, et al. Effective protection for > 5 years with BAY 94-9027 prophylaxis: interim results from the PROTECT VIII extension trial [abstract plus poster]. In: The 11th Annual Congress of the European Association for Haemophilia and Allied Disorders. 2018.Google Scholar
- 30.Santagostino E, Lalezari S, Ducore J, et al. BAY 94-9027 is efficacious in maintaining hemostasis during major surgery in adults and adolescents with severe hemophilia A: PROTECT VIII results [abstract no. P079]. Haemophilia. 2018;24(Suppl 1):69.Google Scholar
- 31.European Medicines Agency. Jivi (damoctocog alfa pegol): public assessment report. 2019. https://www.ema.europa.eu/. Accessed 6 June 2019.
- 32.Oldenburg J, Michaels LA, Wang M, et al. PROTECT VIII: can patient characteristics predict eligibility for less frequent prophylaxis dosing regimens? [abstract no. PB 1818]. Res Pract Thromb Haemost. 2017;1(Suppl 1):807–8.Google Scholar
- 33.Holme PA, Wang M, Saxena K, et al. Predictors of patients with 0 bleeds during every-7-days prophylaxis with BAY 94-9027 in PROTECT VIII [abstract no. PB 1780]. Res Pract Thromb Haemost. 2017;1(Suppl 1):786–7.Google Scholar
- 34.Santagostino E, Kerlin BA, Negrier C, et al. Characteristics of bleed-free patients on every-5-day dosing in the PROTECT VIII (BAY 94–9027) study [abstract]. Blood. 2018;132(Suppl 1):2486.Google Scholar
- 35.Linardi C, Enriquez MM, Lalezari S. BAY 94-9027 prophylaxis improves quality of life: Haemo-QoL-A data from the PROTECT VIII study [abstract no. W-P-010 (737)]. Haemophilia. 2018;24(Suppl 5):21–2.Google Scholar
- 36.Kerlin BA, Simpson ML, Reding MT, et al. Comparison of bleeding rates before and during BAY 94-9027 prophylaxis: data from the PROTECT VIII study and extension [abstract plus poster]. In: 4th Biennial Summit of the Thrombosis and Hemostasis Societies of North America. 2018.Google Scholar
- 37.Pabinger I, Oldenburg J, Huth-Kuhne A, et al. Prophylaxis with extended dosing of BAY 94-9027 decreases overall and joint bleeding rates with consistent consumption for over 4 years of treatment [abstract no. P09-5]. In: Annual Meeting of the Society of Thrombosis and Haemostasis Research. 2019.Google Scholar
- 38.Reding MT, Ng HJ, Tseneklidou-Stoefer D, et al. Safety of long-term prophylaxis with BAY 94-9027: interim results of >5 years of treatment in the PROTECT VIII extension trial [abstract no. W-P-001 (404)]. Haemophilia. 2018;24(Suppl 5):17–8.Google Scholar
- 39.Hanley J, McKernan A, Creagh MD, et al. Guidelines for the management of acute joint bleeds and chronic synovitis in haemophilia: a United Kingdom Haemophilia Centre Doctors’ Organisation (UKHCDO) guideline. Haemophilia. 2017. https://doi.org/10.1111/hae.13201.
- 41.Baxalta US Inc. ADYNOVATE®: US prescribing information. 2016. https://www.fda.gov/. Accessed 6 June 2019.
- 42.European Medicines Agency. Rurioctocog alfa pegol (Adynovi®): EU summary of product characteristics. 2019. https://www.ema.europa.eu/. Accessed 6 June 2019.
- 43.Novo Nordisk Inc. ESPEROCT® [antihemophilic factor (recombinant), glycopegylated-exei]: US prescribing information. 2019. https://www.fda.gov/. Accessed 6 June 2019.
- 45.Shah A, Solms A, Wiegmann S, et al. BAY 94-9027 and recombinant factor VIII Fc fusion protein: a head-to-head, randomized, crossover, pharmacokinetic study in patients with severe haemophilia A [abstract no. P020]. Haemophilia. 2019;25(Suppl 1):45.Google Scholar