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.

Adherence to prophylaxis and bleeding outcome: A multicenter Nigerian study

“…It may improve adherence as it offers the convenience of once a week, 2 weekly or 4 weekly dosing by subcutaneous administration. Other agents with different non-replacement mechanisms and prophylaxis regimens (dosing/frequency of administration) are on clinical trials [ 11 , 12 ]. These approaches are not associated with a peak and trough effects and are not measurable with standard laboratory methods, however they provide a protection comparable to factor levels of patients with mild hemophilia [ 11 , 12 ].…”

“…Other agents with different non-replacement mechanisms and prophylaxis regimens (dosing/frequency of administration) are on clinical trials [ 11 , 12 ]. These approaches are not associated with a peak and trough effects and are not measurable with standard laboratory methods, however they provide a protection comparable to factor levels of patients with mild hemophilia [ 11 , 12 ]. Overall, non-replacement agents could be very useful to facilitate early implementation and long-term management of prophylaxis, thus improving adherence particularly in the case of problems of venous access, like in children.…”

“…Other agents with different non-replacement mechanisms are on clinical trials. However costs of non-replacement agents limit the availability for prophylaxis in low-income countries [ 11 , 12 ]. The objectives of prophylaxis in different situations vary depending on the patient’s age and underlying conditions [ 13 ].…”

Shifting Paradigms and Arising Concerns in Severe Hemophilia A Treatment

“…These applications can also notify patients when they reach critical factor levels to prevent missed FVIII infusions. 144 However, whether the local patient population will stay committed to using these tools to obtain PK data remains uncertain. Depending on PK for bleeding control may be unreliable if the standard of home monitoring is unsatisfactory.…”

Patient Perspective on Disease Burden and Gene Therapy for Hemophilia A and B: The “Haemvolution for Patients” Italian Survey

“…4 Despite the advances in hemophilia treatments, including the development of extended half-life (EHL) concentrates and nonreplacement subcutaneous therapy, 2 9 none of these therapeutic approaches provide sustained normalization of hemostasis. 11…”