Abstract

Background

Hemophilia A with or without inhibitors to factor VIII (FVIII) has a major impact on the quality of life of people with this condition. This may be exacerbated by the treatment burden associated with current factor treatments that require frequent IV administration to reduce the risk of bleeding. Previous studies have noted that patients favor treatments that have a goal of achieving a "normal life" and avoid negative effects (e.g. infusion-related pain, time-consuming, or high treatment burden) (Cimino et al. Patient Prefer Adherence 2014). Two Phase III studies recently demonstrated the efficacy and safety of subcutaneous emicizumab administered weekly (QW) or every 2 weeks (Q2W) in persons with hemophilia A (PwHA) without inhibitors (HAVEN 3; NCT02847637; Mahlangu et al. N Engl J Med 2018, in press), and every 4 weeks (Q4W) in PwHA with or without inhibitors (HAVEN 4; NCT03020160; Pipe et al. WFH 2018). The studies included questionnaires developed and validated to investigate patients' preference and satisfaction with emicizumab compared with prior treatment.

Methods

In HAVEN 3, PwHA without inhibitors aged ≥12 years on prior episodic FVIII were randomized 2:2:1 to receive emicizumab QW (Arm A), Q2W (Arm B), or to no prophylaxis control (Arm C). Patients on prior prophylactic FVIII received emicizumab QW (Arm D). In HAVEN 4, PwHA with or without inhibitors aged ≥12 years with prior episodic bypassing agents (BPAs) or prophylactic FVIII received emicizumab Q4W. Patient preference was assessed through the Emicizumab Preference Survey (EmiPref) at Week 17 in both studies when patients had gained sufficient experience with emicizumab, potential bias due to anticipation associated with being in a study subsided, and they could still reliably recall their experience with prior therapy. The survey included three questions: patients were initially asked which they preferred - previous hemophilia treatment, new study treatment, or no preference. Those expressing a preference were then asked to rank the top three reasons for their choice. Finally, patients could provide additional free text related to their experience with emicizumab. Treatment satisfaction was assessed in Arm D of HAVEN 3 using the Satisfaction Questionnaire - Intravenous Subcutaneous Hemophilia Injection (SQ-ISHI). This 16-item questionnaire was to be completed at baseline and then either Week 21 or 25 after initiation of emicizumab.

Results

EmiPref was completed by 95/134 patients (71%) from Arms A, B, or D in HAVEN 3. Eighty-nine patients (94%) preferred emicizumab to their previous treatment and only 2 (2%) favored their previous treatment. The most frequent reasons selected for preference included a more convenient mode of administration ("frequency of treatments was lower" and "route of administration was easier") and reduced concern of bleeds ("worries about having bleeds were less"), reflecting the superior efficacy demonstrated in this study. In HAVEN 4, all 41 (100%) participants completed the EmiPref survey and all (100%) reported preferring emicizumab to their prior treatment. The most frequent reasons selected for preference were "the frequency of treatments was lower", followed by "the route of administration was easier", and "quality of life, in general, was better". When patients in HAVEN 3 and 4 were examined together, 99% (75/76) of patients who received prior FVIII or BPA prophylaxis favored emicizumab. Of the patients receiving prior episodic treatment, 92% (55/60) preferred emicizumab. Notably, all participants in HAVEN 3 and 4 continue to receive emicizumab beyond the primary analysis, including those who did not report favoring emicizumab, confirming the preference for emicizumab. The results of the SQ-ISHI completed by 50 patients in Arm D of HAVEN 3 at Week 21 indicated that 90% of patients were "much more" or "a lot more satisfied" with their current emicizumab prophylaxis compared with their pre-study treatment.

Conclusions

Almost all patients in HAVEN 3 and all patients in HAVEN 4 preferred emicizumab to their prior treatment. These results likely reflect the high efficacy and lower treatment burden previously reported. Such strong preference will be important for individuals currently receiving either episodic or prophylactic treatment when considering emicizumab prophylaxis in the future and may be associated with improved adherence, a substantial clinical obstacle with FVIII or BPAs.

Disclosures

Jimenez-Yuste:Roche: Consultancy, Research Funding; Shire: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Sobi: Consultancy, Research Funding; Octapharma: Consultancy, Research Funding; CSL Behring: Consultancy; Grifols: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; NovoNordisk: Consultancy, Research Funding. Shima:F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees; Chugai Pharmaceutical Co., Ltd: Consultancy, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Anti-FIXa/X bispecific antibodies , Research Funding, Speakers Bureau. Paz-Priel:Genentech Inc: Employment. Parnes:Genentech Inc: Research Funding; Biogen Idec: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Shire: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees. Lehle:F. Hoffmann-La Roche: Employment. Giermasz:Bioverative, Biomarin, Genentech, Spark, Opko: Research Funding; Bioverativ, Biomarin, Genentech, Alexion, Bayer: Membership on an entity's Board of Directors or advisory committees. Campinha-Bacote:Genentech Inc: Employment. Niggli:F. Hoffmann-La Roche: Employment. Windyga:Alexion, Baxalta, Bayer, CSL Behring, Ferring Pharmaceuticals, Novo Nordisk, Octapharma, Rigel Pharmaceuticals, Roche, Sanofi, Shire, Siemens, SOBI, Werfen: Membership on an entity's Board of Directors or advisory committees; Alnylam, Baxalta, Bayer, Novo Nordisk, Octapharma, Rigel Pharmaceuticals, Roche, Sanofi, Shire, SOBI: Research Funding. Chebon:F. Hoffmann-La Roche: Employment. Trask:F. Hoffmann-La Roche: Employment; Genentech Inc: Employment. Mahlangu:Alnylam: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy; Bayer: Research Funding; Biogen: Research Funding, Speakers Bureau; Biomarin: Research Funding, Speakers Bureau; Catalyst Biosciences: Consultancy, Research Funding; Chugai: Consultancy; CSL Behring: Consultancy, Research Funding, Speakers Bureau; NovoNordisk: Consultancy, Research Funding, Speakers Bureau; LFB: Consultancy; Roche: Consultancy, Research Funding, Speakers Bureau; Sanofi: Research Funding, Speakers Bureau; Shire: Consultancy, Research Funding, Speakers Bureau; Sobi: Research Funding, Speakers Bureau; Spark: Consultancy, Research Funding. Pipe:Apcintex: Consultancy; Catalyst Biosciences: Consultancy; Genentech: Consultancy; Spark Therapeutics: Consultancy; Pfizer: Consultancy; CSL Behring: Consultancy; Bioverativ: Consultancy; R2 Diagnostics: Research Funding; HEMA Biologics: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy; Ainylam: Consultancy; Freeline: Consultancy; Bayer: Consultancy; uniQure: Consultancy; Biomarin: Consultancy; Nove Nordisk: Consultancy; Shire: Consultancy, Research Funding; Siemens: Research Funding. Oldenburg:Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria, Membership on an entity's Board of Directors or advisory committees; Biogen Idec: Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biotest: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Swedish Orphan Biovitrum: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Author notes

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Asterisk with author names denotes non-ASH members.