Efficacy and safety of damoctocog alfa pegol prophylaxis in patients ⩾40 years with severe haemophilia A and comorbidities: post hoc analysis from the PROTECT VIII study

Abstract

Background: Advances in treatment have enabled patients with haemophilia A to live longer and therefore may be subjected to comorbidities associated with ageing, in addition to disease-associated morbidities. There have been few reports to date on efficacy and safety of treatment specifically in patients with severe haemophilia A and comorbidities.

Objective: To explore the efficacy and safety of damoctocog alfa pegol prophylaxis in patients with severe haemophilia A aged ⩾40 years with comorbidities of interest.

Design: A post hoc analysis of data from the phase 2/3 PROTECT VIII study and its extension.

Methods: Bleeding and safety outcomes were analysed in a subgroup of patients aged ⩾40 years with ⩾1 comorbidity receiving damoctocog alfa pegol (BAY 94-9027; Jivi®) prophylaxis.

Results: Thirty-four patients with severe haemophilia A were included in this analysis, with a mean age of 49.4 years at time of enrolment. The most prevalent comorbidities were hepatitis C (n = 33; chronic, n = 23), hepatitis B (n = 8) and hypertension (n = 11). Four patients had human immunodeficiency virus. All received damoctocog alfa pegol prophylaxis for the entire study [median (range) time in study = 3.9 (1.0-6.9) years]. During the main study and extension, median total annualised bleeding rates (ABRs) (Q1; Q3) were 2.1 (0.0; 5.8) and 2.2 (0.6; 6.0), respectively; median joint ABRs were 1.9 (0.0; 4.4) and 1.6 (0.0; 4.0), respectively. Mean adherence with prophylaxis schedule was greater than 95% throughout the study. No deaths or thrombotic events were reported.

Conclusion: Efficacy, safety and adherence of damoctocog alfa pegol were confirmed in patients aged ⩾40 years with haemophilia A and one or more comorbidities, with data for up to 7 years supporting its use as a long-term treatment option in this group.

Plain language summary: Advances in treatment mean that people with haemophilia A are now living longer and, as a result, may have additional medical conditions that occur with ageing. We aimed to investigate the efficacy and safety of the long-acting replacement factor VIII damoctocog alfa pegol in people with severe haemophilia A who had additional medical conditions. To do this, we investigated the recorded information about patients aged 40 years of age or older who had been treated with damoctocog alfa pegol in a previously completed clinical trial. We found that the treatment was well-tolerated; no deaths or thrombotic events (undesirable clotting events) were reported. Treatment was efficacious in reducing bleeding in this group of patients. The findings support the use of damoctocog alfa pegol as a long-term treatment for older patients with haemophilia A and coexisting conditions.

Keywords: PEGylated; comorbidities; extended half-life; haemophilia A; prophylaxis.

Conflict of interest statement

The authors declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: M.T.R. has received grants and research support from Bayer and BioMarin; honoraria and consultation fees from Bayer, CSL Behring, Novo Nordisk, Sanofi Genzyme and Takeda and participates in a company sponsored speakers bureau for Bayer, CSL Behring, Sanofi Genzyme and Takeda. I.P. has received honoraria for lectures and advisory board meetings from Bayer, Biotest, CSL Behring, Octapharma, Pfizer, Shire, Novo Nordisk, Sobi, Roche, and has received unrestricted research grants from CSL Behring and Novo Nordisk. P.A.H. has received grants and research support from Bayer, Octapharma, Pfizer, and Shire; and consultation fees from Bayer, Novo Nordisk, Octapharma, Pfizer, Shire and Sobi. M.M.E. is an employee at Bayer. M.E.M. has received honoraria and consultation fees from Bayer, Bioverativ, Catalyst, CSL Behring, Grifols, Kedrion, Novo Nordisk, Octapharma, Pfizer, Roche, BioMarin, Shire/Takeda and Sobi; participates in a company sponsored speakers bureau for Bayer, CSL Behring, Grifols, Kedrion, Novo Nordisk, Octapharma, Pfizer, Roche, BioMarin, Shire/Takeda and Sobi. S.L. has participated in advisory boards for Bayer; and received honoraria or consultation fees from Bayer, Teva Pharmaceuticals, Takeda, PI Healthcare, Roche and Pfizer. W.M. has received grant and research support from Bayer, Biotest, CSL, LFB, Novo Nordisk, Octapharma, Pfizer, Sobi, Takeda and UniQure; received consultation fees from BioMarin, Freeline, LFB, Octapharma, Sobi, Novartis, Novo Nordisk, Octapharma, Pfizer and Roche; and participated in speaker bureaux for Shire, Pfizer, Bayer, Sobi, Amgen, Novartis, Alexion, Leo Pharma, Grifols, Roche and Novo Nordisk. G.D.M. has participated in speaker bureaux for Bayer, CSL Behring, Novo Nordisk, Pfizer, Sobi and Takeda; and has received consultancy or speaker fees from Bayer, Novo Nordisk, Pfizer, Sanofi Aventis and Sobi. R.K. has received grants and research support from Bayer, Novo Nordisk and Sobi; honoraria and consultation fees from Bayer, BioMarin, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, Sobi and Takeda; participates in a company sponsored speakers bureau for Bayer, BioMarin, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, Sobi and Takeda. C.H. provides paid consultancies and has received invitations to give lectures for Shire, Pfizer, Bayer, Octapharma, LFB, CAF-DCF, Roche, Novo Nordisk, CSL Behring, Sobi Bioverativ and Kedrion.

© The Author(s), 2023.

Figures

Figure 1.

Total and joint ABRs prestudy, during PROTECT VIII main study and extension in patients with comorbidities aged ⩾40 years (n = 34), and by prior FVIII treatment type. *Prestudy data were available for only 27 patients receiving prior FVIII prophylaxis. ABR, annualised bleeding rate; Q, quartile.