Unmet Needs of Patients with Hemophilia a/B with or without Inhibitors: Real-World End-of-Study Results from the explorer6 Non-Interventional Study

Background:

Unmet needs associated with hemophilia and its treatment persist, including repeated bleeding episodes, reduced physical activity, treatment burden, and the development of antibodies with resultant limited treatment options (Putz P et al. Haemophilia 2021; 27(2):e260-e266; Ljung R et al. Eur J Haematol 2019;102(2):111-122). Evaluating data from patients with hemophilia prospectively would help to better define existing unmet needs and assist in optimizing treatment and improving healthcare outcomes. explorer6 (NCT03741881) was a prospective, multi-national, non-interventional study in patients with hemophilia (hemophilia A or B without inhibitors [HA or HB] or with inhibitors [HAwI or HBwI]).

Aims:

To communicate end-of-study data from explorer6 in routine clinical practice, focusing on bleeding episodes and physical activity.

Methods:

Male patients aged ≥12 years with severe HA, severe/moderate HB, or HAwI/HBwI of any severity were recruited. Each patient was treated according to their center's standard of care. The primary objective was to investigate the number of bleeding episodes from enrolment up to a maximum of 115 weeks in routine clinical treatment practice. Exploratory objectives included assessment of physical activity, based on data collected by a wrist-worn physical activity tracker, from enrolment for a duration of 3-12 weeks. Hemophilia Joint Health Score (HJHS) measurements were reported, if available. All statistics are descriptive and exploratory. Results are presented according to treatment regimen at end of study (on-demand [OnD] or prophylaxis [PPX]), hemophilia type (HA or HB) and inhibitor status (with or without inhibitors). Informed consent/ethics committee approval were obtained.

Results:

A total of 231 patients from 109 clinical centers across 33 countries were enrolled. There were 138 patients without inhibitors (HA: 70; HB: 68) and 80 patients with inhibitors (HAwI: 49; HBwI: 31) who completed the study. Most patients (97.8%) had severe hemophilia, and five patients (HB and HAwI) had mild to moderate hemophilia. For treated bleeding episodes, the mean annualized bleeding rate [ABR] (SD) for HA and HB receiving OnD treatment was 21.5 (17.7) and 10.5 (8.6), respectively, and for PPX 4.7 (5.9) and 2.2 (3.0), respectively. The mean ABR (SD) for HAwI and HBwI receiving OnD treatment was 15.2 (14.8) and 9.3 (13.3), respectively, and for PPX 10.3 (8.5) and 12.4 (14.1), respectively. Physical activity levels (moderate or vigorous), reported as a mean percentage of awake time, were similar for patients on PPX (HA: 13.7%; HB: 16.3%; HAwI: 12.6%; HBwI: 11.6%) versus those receiving OnD treatment (HA: 12.3%; HB: 13.9%; HAwI: 14.2%; HBwI: 10.2%). Physical activity levels were lowest among patients with HBwI. HJHS data were available for 130 (56.3%) patients, and mean HJHS results were numerically lower or similar for PPX (HA: 16.2; HB: 8.8; HAwI: 19.1) compared with OnD (HA: 25.1; HB: 31.0; HAwI: 23.9). Mean HJHS results for HBwI were similar for patients receiving PPX (HBwI: 23.7) and OnD treatment (HBwI: 22.3).

Conclusions:

The explorer6 study assessed bleeding episodes and physical activity in routine clinical practice in patients with hemophilia, including a large HBwI population (31/231 patients; 13.4%). The data reported indicate that an unmet need still exists in patients with inhibitors, as evidenced by increased bleeding events and HJHS results, as well as decreased physical activity. This is particularly pertinent for those with HBwI for whom no efficacious PPX treatment regimen is available. These unmet needs emphasize the necessity for new therapeutic options to improve healthcare outcomes.

Wheeler:HEMA Biologics: Honoraria; Bayer: Honoraria; Bioverativ: Honoraria; Spark Therapeutics: Honoraria; Takeda Pharmaceuticals: Honoraria; Genentech: Honoraria; Shire North America: Honoraria; Octapharma: Research Funding; CSL Behring: Honoraria; BioMarin: Honoraria; Novo Nordisk: Consultancy, Honoraria, Research Funding; Octapharma USA: Honoraria; Pfizer Inc: Honoraria; Sanofi-Aventis USA: Honoraria. Abraham:Novo Nordisk: Honoraria, Other: Travel Grant, Research Funding; Roche: Other: Travel Grant, Research Funding. Barnes:Novo Nordisk: Research Funding. Brown Frandsen:Novo Nordisk: Current Employment, Research Funding. Hampton:Novo Nordisk: Research Funding, Speakers Bureau; Sobi: Speakers Bureau; Octapharma: Speakers Bureau. López Jaime:Pifzer: Consultancy, Honoraria, Speakers Bureau; Novartis: Speakers Bureau; Novo Nordisk: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sobi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; CSL Behring: Consultancy, Honoraria, Research Funding, Speakers Bureau; Octapharma: Consultancy, Honoraria, Speakers Bureau; Leo Pharma: Speakers Bureau; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Rovi: Speakers Bureau. Martins Mazini Tavares:Novo Nordisk: Current Employment, Research Funding. Nogami:Chugai Pharmaceutical Co.: Consultancy, Other: principal investigator, Research Funding; Bioverativ: Other: principal investigator, Research Funding; Sanofi S.A.: Consultancy, Other: principal investigator, Research Funding; Bayer AG.: Consultancy, Other, Research Funding; Novo Nordisk A/S: Consultancy, Other: principal investigator, Research Funding; CSL Behring Co.: Consultancy, Other: principal investigator, Research Funding; Sysmex Co.: Consultancy, Other, Research Funding; KM Biologics Co.: Consultancy, Other: principal investigator, Research Funding; Fujimoto Pharmaceutical Co.: Consultancy, Other, Research Funding; Sekisui medical: Consultancy, Other: principal investigator, Research Funding. Windyga:Alnylam, Amgen, AstraZeneca, Bayer AG, CSL Behring, LFB, Novartis, Novo Nordisk, Octapharma, Pfizer, Roche, Sanofi, Siemens, Sobi, Takeda, Werfen: Honoraria; Alnylam, Amgen, AstraZeneca, LFB, Novartis, Novo Nordisk, Roche, Sanofi, Sobi, Takeda: Research Funding; Amgen, AstraZeneca, Novartis, Novo Nordisk, Octapharma, Pfizer, Roche, Sanofi, Siemens, Sobi, Takeda, Werfen: Speakers Bureau; Amgen, AstraZeneca, Novartis, Novo Nordisk,Pfizer, Roche, Sanofi, Sobi, Takeda, Werfen: Consultancy; Amgen, AstraZeneca, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Takeda: Membership on an entity's Board of Directors or advisory committees. Castaman:Takeda: Honoraria, Other: participant of advisory boards, Speakers Bureau; Grifols: Speakers Bureau; Roche: Consultancy, Honoraria, Other: participant of advisory boards , Speakers Bureau; Grifols: Speakers Bureau; Werfen: Speakers Bureau; Pfizer: Honoraria, Other: participant of advisory boards ; 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 ; Novo Nordisk: Honoraria, Other: participant of advisory boards , Research Funding, Speakers Bureau; BioMarin: Honoraria, Other: participant of advisory boards, Speakers Bureau; Bioviiix: Speakers Bureau; Bayer: Honoraria, Other: participant of advisory boards ; Sobi: Honoraria, Other: participant of advisory boards , Speakers Bureau; Bioverativ: Honoraria, Speakers Bureau; CSL Behring: Honoraria, Other: participant of advisory boards ; LFB: Honoraria, Other: participant of advisory boards , Speakers Bureau.