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Jan Astermark,1 Piotr Wojciechowski,2 Samuel Aballéa,3 Zalmai Hakimi,4 Jameel Nazir,4 Robert Klamroth5 1Department of Translational Medicine, Lund University, and Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Malmö, Sweden; 2Creativ-Ceutical, Krakow, Poland; 3Creativ-Ceutical, Rotterdam, the Netherlands; 4Swedish Orphan Biovitrum AB, Stockholm, Sweden; 5Department of Internal Medicine, Hemophilia Treatment Centre, Vivantes Klinikum im Friedrichshain, Berlin, GermanyCorrespondence: Robert Klamroth Email robert.klamroth@vivantes.dePurpose: In patients with hemophilia B, treatment with extended half-life (EHL) recombinant factor IX allows for longer dosing intervals while providing equal or superior bleeding protection compared with standard half-life products. This enables flexible, individualized treatment schedules, which reduce the burden of prophylaxis and improve patient outcomes. This analysis compared the efficacy of recombinant factor IX Fc fusion protein (rFIXFc) and recombinant factor IX albumin fusion protein (rIX-FP), two EHL therapies approved for prophylaxis and treatment of bleeding in hemophilia B.Patients and Methods: Matching-adjusted indirect treatment comparison (MAIC) was used to adjust the between-treatment differences in baseline characteristics. Individual patient data for rFIXFc (B-LONG) were matched to aggregated data for rIX-FP (PROLONG-9FP) followed by statistical comparison for estimated annualized bleeding rate (ABR) using a Poisson regression model with adjustment for over dispersion. Data were analyzed according to treatment regimen prior to study entry: prior prophylaxis (rFIXFc, n=48; rIX-FP, n=40) or prior episodic treatment (n=43 and n=19, respectively). Relative treatment effects are presented as incidence rate ratios (IRR) with 95% confidence intervals (CI).Results: After adjustment for baseline characteristics, estimated ABR observed for rFIXFc and rIX-FP was not significantly different in patients on prior prophylaxis (1.87 versus 1.58; IRR 1.18, 95% CI 0.67– 2.10) or prior episodic (2.25 versus 2.22; IRR 1.01 95% CI 0.40– 2.57) regimens.Conclusion: This MAIC analysis shows that the estimated ABR for rFIXFc-treated patients from B-LONG was similar to that of rIX-FP-treated patients from PROLONG-9FP and, therefore, indicates that the two EHL therapies provide similar efficacy when used as prophylaxis for patients with hemophilia B. Trough levels differ between the two products (1– 3% [targeted] versus 20% [observed], respectively), suggesting that trough level is not a surrogate indicator when ABR is used as a criterion for clinical efficacy when comparing these FIX products in hemophilia B.Keywords: annualized bleeding rate, comparative effectiveness research, factor IX deficiency, factor IX Fc fusion protein, rIX-FP fusion protein, treatment outcome

Robert Klamroth,1 Piotr Wojciechowski,2 Samuel Aballéa,3 Françoise Diamand,4 Zalmai Hakimi,5 Jameel Nazir,5 Lydia Abad-Franch,6 Stefan Lethagen,7 Elena Santagostino,8 Michael D Tarantino9 1Department of Internal Medicine, Hemophilia Treatment Centre, Vivantes Klinikum im Friedrichshain, Berlin, Germany; 2Creativ-Ceutical, Krakow, Poland; 3Creativ-Ceutical, Rotterdam, the Netherlands; 4Creativ-Ceutical, Paris, France; 5Health Economics and Outcomes Research (Global), Sobi, Stockholm, Sweden; 6Global Medical Affairs Hematology, Sobi, Stockholm, Sweden; 7Medical and Clinical Sciences, Sobi, Stockholm, Sweden; 8Medical Affairs Hematology, Sobi, Stockholm, Sweden; 9The Bleeding and Clotting Disorders Institute, University of Illinois College of Medicine-Peoria, Peoria, IL, USACorrespondence: Robert KlamrothDepartment of Internal Medicine – Angiology and Hemostaseology, Center for Vascular Medicine, Hämophiliezentrum/Gerinnungssprechstunde, Vivantes Klinikum im Friedrichshain, Landsberger Allee 49, D, Berlin, 10249, Germany, Tel +49 (0)30 130 231575Fax +49 (0)30 130 231313Email robert.klamroth@vivantes.dePurpose: Primary prophylaxis, using factor VIII replacement, is the recognized standard of care for severe hemophilia A. Recombinant factor VIII-Fc fusion protein (rFVIIIFc) and emicizumab, a humanized, bispecific antibody, are approved for routine prophylaxis of bleeding episodes in severe hemophilia A. These products have different mechanisms of action, methods of administration and treatment schedules. In the absence of head-to-head trials, indirect treatment comparisons can provide informative evidence on the relative efficacy of the two treatments. The aim of the study was to compare the approved dosing regimens for each product, rFVIIIFc individualized prophylaxis and emicizumab administered once every week (Q1W), every 2 weeks (Q2W) or every 4 weeks (Q4W), based on clinical trial evidence.Patients and Methods: The comparison was conducted using matching-adjusted indirect comparison since clinical evidence did not form a connected network. Individual patient data for rFVIIIFc (A-LONG) were compared with data for emicizumab (HAVEN trial program) for mean annualized bleeding rate (ABR) and proportion of patients with zero bleeds. Safety data reported across the analyzed treatment arms were tabularized but not formally compared.Results: After matching, no significant differences were observed between mean ABR for rFVIIIFc and emicizumab administered Q1W, Q2W or Q4W. The proportion of patients with zero bleeds was significantly higher with rFVIIIFc compared with emicizumab administered Q4W (51.2% versus 29.3%, respectively; odds ratio 2.53; 95% confidence interval 1.09– 5.89); no significant differences noted when rFVIIIFc was compared with emicizumab administered Q1W or Q2W. The mean number of adverse events expressed per participant was 1.9 for individualized prophylaxis with rFVIIIFc and 3.7– 4.0, 4.1 and 3.6 for emicizumab administered Q1W, Q2W or Q4W, respectively.Conclusion: This indirect treatment comparison suggests that rFVIIIFc individualized prophylaxis is more efficacious than emicizumab Q4W, and at least as effective as more frequent emicizumab regimens, for the management of hemophilia A.Keywords: annualized bleeding rate, antibodies, bispecific, comparative effectiveness research, efmoroctocog alfa, factor VIII deficiency, treatment outcome

Gorden Muduma,1 Francis C Shupo,2 Sophie Dam,3 Natalia A Hawken,3 Samuel Aballéa,3 Isaac Odeyemi,1 Mondher Toumi4 1Astellas Pharma Europe Ltd, Chertsey, 2Creativ-Ceutical Ltd, London, UK; 3Creativ-Ceutical Ltd, Paris, 4Public Health (EA 3279), Faculty of Medicine, Aix-Marseille University, Marseille, France Background: Renal transplantation (RT) is considered the treatment of choice for end-stage renal disease compared to dialysis, offering better health-related quality of life (HRQoL) and higher survival rates. However, immunosuppressants are essential for the long-term survival of kidney grafts and patients’ non-adherence to their medication leads to poor outcomes. Immunosuppressants can also significantly alter patients’ HRQoL because of their side effects and the complex chronic medication regimen they represent. Purpose: To elicit key concepts related to adherence to immunosuppressant therapy (IT) and reasons for non-adherence in terms of patient reported outcomes, side effects, and the impact of the medication on HRQoL in RT population, including patient preference of once daily over twice-daily immunosuppressive regimen. Results were used to develop an IT-specific conceptual framework and provide suggestions for improving patients’ adherence to IT. Materials and methods: Interviews were conducted with three clinical experts to determine key concepts related to RT and immunosuppressants. Thirty-seven participants in four focus groups were asked to cite important concepts related to adherence and impact of IT on HRQoL and to rate them. Qualitative analysis was conducted to code participants’ responses. Results: Non-adherence among participants where admitted was unintentional. The reason for this included forgetfulness, interference with lifestyle, being asleep at the time the medication should be taken, change in routine, and impact of side effects. Overall, participants reported that the evening dose was more problematic to remember and that the exclusion of this dose could make them more adherent. Participants also reported that IT impacted on their HRQoL in a number of ways including: placing restrictions on their lifestyle, causing anxiety, or impairing their ability to work. Conclusion: This study provides qualitative evidence about the barriers to IT adherence and the components of HRQoL that are important from the perspective of RT patients. The developed conceptual framework of IT-HRQoL in RT transplants, including social, psychological, and work life domains, can be used to inform the development of a new IT-specific measure of HRQoL in RT patients for use in head-to-head clinical trials or observational studies. Despite limitations associated with the number and the age range of patients recruited, this study suggests that a change in the regimen from twice-daily to once daily among other measures could improve their adherence to IT and their HRQoL by placing less restrictions on their lifestyles. Keywords: adherence, PRO, conceptual framework, immunosuppressant, renal transplantation, QoL