Marstacimab Cost-Effectiveness Analysis in Hemophilia Treatment: A Portuguese Assessment
The public assessment report for Hympavzi (marstacimab) in Portugal concludes that the product offers no added therapeutic value relative to recombinant factor VIII concentrates and emicizumab in patients aged 12 years and older weighing at least 35 kg with severe hemophilia A without factor VIII inhibitors, or relative to recombinant factor IX concentrates in the corresponding severe hemophilia B population. Despite this finding, the report identifies a beneficial effect of the product itself and therefore recommends public funding under Portuguese legislation. The Marstacimab cost-effectiveness analysis, conducted as a cost-minimization analysis, demonstrated an advantage for marstacimab over the selected comparators, leading to subsequent price negotiations to secure more favorable conditions for the National Health Service.
Clinical Outcomes Versus Economic Efficiency
The report establishes that marstacimab, a human IgG1 monoclonal antibody targeting the Kunitz-2 domain of tissue factor pathway inhibitor, did not demonstrate superiority in annualized bleeding rate or other critical outcomes when compared indirectly with emicizumab in the hemophilia A subpopulation without inhibitors. The simulated treatment comparison, adjusted for selected effect modifiers and prognostic factors, yielded a rate ratio of 1.08 (95 % CI 0.61–1.91) for total annualized bleeding rate and an odds ratio of 0.64 (95 % CI 0.26–1.60) for the proportion of patients with zero bleeding events, neither of which reached statistical significance. No direct or indirect comparative data were available against recombinant factor concentrates for either hemophilia A or B. Nevertheless, the Marstacimab cost-effectiveness analysis indicated lower overall treatment costs for marstacimab, prompting further negotiation to optimize value for the health system.
Evidence Quality and Portuguese Patient Context
The evaluation rests on a single-arm, open-label phase 3 study (BASIS) and its extension, supplemented by a systematic literature review and an unanchored simulated treatment comparison. The BASIS trial enrolled 145 participants aged 12–74 years with severe or moderately severe hemophilia A or B, with or without inhibitors, and compared a six-month observational period of standard factor replacement with a subsequent 12-month period of weekly subcutaneous marstacimab. Because the design lacked a randomized comparator arm aligned with the defined PICO matrix, the Commission classified the overall evidence quality as very low. Epidemiological data cited in the report indicate approximately 830 patients with hemophilia A and 209 with hemophilia B under follow-up in Portuguese reference centers, underscoring the small but high-cost patient population for which prophylaxis decisions carry substantial budget impact.
Reimbursement Balance in Hemophilia Care
The recommendation to fund marstacimab despite the absence of proven added therapeutic value illustrates how Portuguese authorities balance clinical uncertainty with economic considerations and statutory requirements for patient access. The subsequent negotiation phase, conducted under Decree-Law 97/2015, aims to translate the cost-minimization advantage into concrete savings for the National Health Service while ensuring appropriate use in hospital settings through a managed-entry agreement. For Health Economics and Outcomes Research (HEOR) practitioners, this case demonstrates the growing weight placed on budget-impact and cost-minimization analyses when randomized comparative evidence is unavailable, and it signals that future submissions for hemophilia products will likely face similar scrutiny regarding both clinical differentiation and sustainable pricing.
