Expert opinion on current and future prophylaxis therapies aimed at improving protection for people with hemophilia A

Abstract

The next frontier in hemophilia A management has arrived. However, questions remain regarding the broader applicability of new and emerging hemophilia A therapies, such as the long-term safety and efficacy of non-factor therapies and optimal regimens for individual patients. With an ever-evolving clinical landscape, it is imperative for physicians to understand how available and future hemophilia A therapies could potentially be integrated into real-life clinical practice to improve patient outcomes. Against this background, nine hemophilia experts from Central European countries participated in a pre-advisory board meeting survey. The survey comprised 11 multiple-choice questions about current treatment practices and future factor and non-factor replacement therapies. The survey questions were developed to reflect current unmet needs in hemophilia management reflected in the literature. The experts also took part in a follow-up advisory board meeting to discuss the most important unmet needs for hemophilia management as well as the pre-meeting survey results. All experts highlighted the challenge of maintaining optimal trough levels with prophylaxis as their most pressing concern. Targeting trough levels of ≥30-50 IU/L or even higher to achieve less bleeding was highlighted as their preferred strategy. However, the experts had an equal opinion on how this could be achieved (i.e., more efficacious non-factor therapies or factor therapy offering broader personalization possibilities such as targeting trough levels to individual pharmacokinetic data). In summary, our study favors personalized prophylaxis to individual pharmacokinetic data rather than a "one-size-fits-all" approach to hemophilia A management to maintain optimal trough levels for individual patients.

Keywords: ABR – annualized bleed rate; BPAs – bypassing agents; BU – Bethesda units; EHL – extended half-life; FVIII/IX – factor VIII/IX; ITI – immune tolerance induction; PPX – prophylaxis; QoL – quality of life; SHL – standard half-life; TFPI – tissue factor pathway inhibitor; TGA – thrombin generation assays; WFH – World Federation of Hemophilia; aPCC – activated prothrombin complex concentrates; extended half-life; hemophilia; mHJHS – modified Haemophilia Joint Health Score; pd – plasma-derived; prophylaxis; r – recombinant; rFVIIIFc – recombinant FVIII Fc fusion protein; rFVIIIpeg – recombinant pegylated FVIII; siRNA – small interfering RNA.

Figure 1.

Question: "Reflecting your clinical practice, which of the following have you observed when introducing/switching to EHL (e.g., rFVIIIFc) from SHL (pdFVIII or rFVIII) products?". Experts selected all options that applied. ABR – annualized bleeding rate; EHL – extended half-life; rFVIII – recombinant factor VIII; rFVIIIFc – rFVIII fusion protein; pdFVIII – plasma-derived factor VIII; SHL – standard half-life.

Figure 2.

Question: "Based on your clinical experience and available data from the literature, what is your opinion on maintenance of joint health with factor and non-factor therapies?". Experts selected all options that applied. EHL – extended half-life.

Figure 3.

Question: "In your opinion, is factor or non-factor therapy more efficacious when aiming for 3–5% trough in hemophilia A prophylaxis?". sABR – spontaneous annualized bleeding rate.

Figure 4.

Question: "What would you expect if factor prophylaxis in hemophilia A is intensified to aim for 10% trough?". AUC – area under curve.

Figure 5.

Question: "In your opinion, how can quality of life (QoL) be improved for people with hemophilia A, ranking 1–5, 1 being most important?".