Fourth Interim Analysis of the Hem Powr Study: A Post Hoc Analysis of Real-World Effectiveness and Safety of Damoctocog Alfa Pegol in Adolescent and Older Patients with Hemophilia a

Introduction: Damoctocog alfa pegol (BAY 94-9027) is an extended half-life recombinant replacement factor VIII (FVIII) product for use in previously treated patients aged ≥12 years with hemophilia A. Previous interim analyses of the HEM-POWR study demonstrated effectiveness and safety of damoctocog alfa pegol. There are age-related considerations in the management of hemophilia. Adolescents may want to pursue a more active lifestyle and play sports as well as coping with transition to independent treatment. An aging population of patients with hemophilia A means that treatment is being managed alongside age-related comorbidities. Additionally, older and younger patients may be underrepresented in clinical trials. This subgroup analysis presents updated data from the fourth interim analysis of HEM-POWR specifically for these age groups of interest, ie, adolescent patients aged ≥12 to <18 years and older patients aged ≥60 years.

Methods: HEM-POWR (NCT03932201) is an ongoing, phase 4, observational, multicenter, and multinational study. The primary endpoint is annualized bleeding rate (ABR) and is assessed in the full analysis set (FAS); secondary endpoints include safety and are assessed in the safety analysis set (SAF). The FAS includes all eligible previously treated patients with bleeding data who received ≥1 documented dose of the study drug in the patient diary. The SAF consists of previously treated patients who received ≥1 dose of study drug during the observation period.

Results: At data cutoff (1 August 2023), overall, there were227 patients included in the FAS and 332 in the SAF. Total median (Q1, Q3) observation period overall was 728.0 (491.0, 876.0) days in the FAS and 624.0 (364.5, 822.5) in the SAF. In the FAS, 33/227 (14.5%) had nonsevere and 190/227 (83.7%) had severe disease (data missing for 4 patients). Of all patients in the FAS,17 were aged ≥12 to <18 years and 21 were aged ≥60 years and have been included in this subgroup analysis. All adolescent and 20/21 (95.2%) older patients were male. There were 3/17 (17.6%) adolescents and 1/21 (4.8%) older patients with a history of inhibitors. Most adolescents did not have a concomitant disease, the most common concomitant disease for older patients was hypertension (n=16, 76.2%). The most common regimen for previous FVIII product prior to damoctocog alfa pegol was every 2 days for adolescents (n=11, 64.7%) and twice weekly for older patients (n=7, 33.3%). At baseline, the most common prophylaxis regimen was twice weekly for adolescents (8/16, 50.0%) and older patients (12/19, 63.2%). Mean (standard deviation [SD])/median (Q1, Q3) ABR for total bleeds in adolescents prior to damoctocog alfa pegol initiation was 2.2 (3.2)/1.0 (0.0, 4.0); during the observation period, ABR was 1.1 (2.2)/0.0 (0.0, 0.8). For this adolescent subgroup, mean (SD)/median (Q1, Q3) difference in ABR from 12 months prior to damoctocog alfa pegol initiation to the observation period was -0.8 (1.7)/0.0 (-1.0, 0.0) for spontaneous bleeds, -1.2 (3.1)/0.0 (-1.0, 0.0) for joint bleeds, and -0.9 (2.1)/0.0 (0.0, 0.0) for spontaneous joint bleeds. Mean (SD)/median (Q1, Q3) ABR for total bleeds in patients aged ≥60 years prior to damoctocog alfa pegol initiation was 2.0 (3.5)/0.0 (0.0, 2.0); during the observation period ABR was 0.8 (1.1)/0.5 (0.0, 1.2) (data missing for 1 patient in the observation period). By bleed type, mean (SD)/median (Q1, Q3) difference in ABR for older patients was -1.0 (2.6)/0.0 (-1.5, 0.0) for spontaneous bleeds, -1.0 (2.4)/0.0 (-1.0, 0.0) for joint bleeds, and -0.8 (2.3)/0.0 (-0.5, 0.0) for spontaneous joint bleeds. In the SAF, 2 adolescents (6.7%) reported serious treatment emergent adverse events (TEAEs), including traumatic cerebral hemorrhage, epileptic absence, and hematuria. In the older subgroup, 3 (9.7%) reported serious TEAEs, including transurethral prostatectomy, rotator cuff syndrome, and injury. There were no deaths, new inhibitors, or study-drug related TEAEs reported in these subgroups.

Conclusions: Results of this analysis demonstrate the consistent effectiveness and acceptable benefit-risk profile of prophylactic damoctocog alfa pegolin patients with hemophilia A regardless of age and challenges associated with this, such as activity level and comorbidities.These findings can inform routine clinical use of damoctocog alfa pegol in adolescent and older patients.

Funded by Bayer.

Reding:Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Biomarin: Research Funding, Speakers Bureau; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; HEMA Biologics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Be Biopharma: Consultancy; Spark: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Alvarez-Román:Roche: Membership on an entity's Board of Directors or advisory committees, Other: Sponsored symposia , Research Funding, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Sponsored symposia , Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Sponsored symposia , Speakers Bureau; Octapharma: Membership on an entity's Board of Directors or advisory committees, Other: Sponsored symposia , Speakers Bureau; Grifols: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Sponsored symposia , Speakers Bureau; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Other: Sponsored symposia , Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Sponsored symposia , Speakers Bureau; Sobi: Membership on an entity's Board of Directors or advisory committees, Other: Sponsored symposia , Speakers Bureau; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Other: Sponsored symposia , Speakers Bureau. Castaman:Grifols: Speakers Bureau; Grifols: Speakers Bureau; Bioviiix: Speakers Bureau; BioMarin: Honoraria, Other: participant of advisory boards, Speakers Bureau; Bayer: Honoraria, Other: participant of advisory boards ; Bioverativ: Honoraria, Speakers Bureau; CSL Behring: Honoraria, Other: participant of advisory boards ; LFB: Honoraria, Other: participant of advisory boards , Speakers Bureau; Novo Nordisk: Honoraria, Other: participant of advisory boards , Research Funding, Speakers Bureau; Pfizer: Honoraria, Other: participant of advisory boards ; Roche: Consultancy, Honoraria, Other: participant of advisory boards , Speakers Bureau; Sobi: Honoraria, Other: participant of advisory boards , Speakers Bureau; Takeda: Honoraria, Other: participant of advisory boards, Speakers Bureau; Werfen: Speakers Bureau; Kedrion: Speakers Bureau; UniQure: Membership on an entity's Board of Directors or advisory committees, Other: participant of advisory boards ; Alexion: Other: participant of advisory boards . Janbain:Takeda: Consultancy, Speakers Bureau; BioMarin: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Genentech: Consultancy; Octapharma: Consultancy; Bayer: Membership on an entity's Board of Directors or advisory committees. Matsushita:Takeda: Consultancy, Honoraria; Chugai: Consultancy, Honoraria, Research Funding; KM Biologics: Honoraria; Sysmex: Honoraria; Sanofi: Honoraria; Novo Nordisk: Consultancy, Honoraria, Research Funding; JB Pharma: Honoraria; Bayer: Consultancy, Honoraria; CSL: Honoraria; Pfizer: Consultancy. Meijer:Bayer: Other: participation in trial steering committee for Bayer; UniQure: Other: consulting fees ; Bayer and Alexion: Other: Speaker fees. Schmidt:Bayer: Current Employment. Oldenburg:Bayer, Biogen Idec, Biomarin, Biotest, Chugai, CSL Behring, Freeline, Grifols, LFB, Novo Nordisk, Octapharma, Pfizer, Roche, Sanofi, Spark Therapeutics, Swedish Orphan Biovitrum and Takeda: Honoraria, Other: reimbursed for attending symposia/congresses , Research Funding.