Novel Approaches for Hemophilia Treatment
Novel Approaches for Hemophilia Treatment
The new products with extended half-life represent important steps toward achieving full benefits of prophylaxis. In addition, extended half-life may have an additional benefit in the treatment of episodic bleeds through a potential reduction in the number of follow-up treatments needed to support complete healing. This advantage was recognized by those who participated in the phase 3 clinical studies with all of the new products that have completed phase 3 trials thus far. When given the choice of an extension study or returning to treatment with their previous standard half-life product, all study participants chose to continue with the extended half-life product.
Because there is significant individual variation in risk of bleeding, as well as in individual pharmacokinetic parameters, selecting one dose or interval regimen is suboptimal, as it may expose patients to avoidable bleeding events or lead to costly overtreatment. Individualized dosing, based either on the use of patient information (eg, experience with previous therapy) to guide empiric selection of dosing regimen, or on laboratory monitoring after initial doses to document actual factor levels, is more systematic and efficient. As the other new products are approved for clinical use, experience in clinical practice will provide further insight into which patients benefit from different new products.
A recombinant product with a longer half-life would be expected to require fewer injections to maintain target factor levels, thus reducing the need for repeated venous access, potentially improving the acceptance of prophylactic regimens. Reduced frequency of dosing would be expected to reduce the number of pediatric patients in whom central venous access devices are required, thus reducing the significant medical complications (infections, sepsis, and thrombosis) that accompany use of central access devices. These advantages should also increase adherence to prophylactic regimens in the pediatric population. Furthermore, the increased half-life should decrease the need for repeated dosing in the treatment of episodic bleeding or in surgical settings.
Use in patients with mild and moderate hemophilia has not been examined yet, but no safety issues would be expected. Hemophilia patients who have a history of developing an inhibitor or an allergic reaction to any factor product were excluded from the clinical trials, so use of the new factor products in these populations has not been examined. One would not expect any issues here either, but clinical experience is needed. Female carriers of hemophilia with low factor activity levels, including pregnant women, were also excluded from the clinical trials. Finally, there are no data on use in patients older than 65 years of age, or for use in previously untreated patients with severe hemophilia. No special problems in any of these populations would be expected, but clinical studies have not been reported.
Implications From the Clinical Studies for Treatment of Hemophilia
The new products with extended half-life represent important steps toward achieving full benefits of prophylaxis. In addition, extended half-life may have an additional benefit in the treatment of episodic bleeds through a potential reduction in the number of follow-up treatments needed to support complete healing. This advantage was recognized by those who participated in the phase 3 clinical studies with all of the new products that have completed phase 3 trials thus far. When given the choice of an extension study or returning to treatment with their previous standard half-life product, all study participants chose to continue with the extended half-life product.
Because there is significant individual variation in risk of bleeding, as well as in individual pharmacokinetic parameters, selecting one dose or interval regimen is suboptimal, as it may expose patients to avoidable bleeding events or lead to costly overtreatment. Individualized dosing, based either on the use of patient information (eg, experience with previous therapy) to guide empiric selection of dosing regimen, or on laboratory monitoring after initial doses to document actual factor levels, is more systematic and efficient. As the other new products are approved for clinical use, experience in clinical practice will provide further insight into which patients benefit from different new products.
A recombinant product with a longer half-life would be expected to require fewer injections to maintain target factor levels, thus reducing the need for repeated venous access, potentially improving the acceptance of prophylactic regimens. Reduced frequency of dosing would be expected to reduce the number of pediatric patients in whom central venous access devices are required, thus reducing the significant medical complications (infections, sepsis, and thrombosis) that accompany use of central access devices. These advantages should also increase adherence to prophylactic regimens in the pediatric population. Furthermore, the increased half-life should decrease the need for repeated dosing in the treatment of episodic bleeding or in surgical settings.
Use in patients with mild and moderate hemophilia has not been examined yet, but no safety issues would be expected. Hemophilia patients who have a history of developing an inhibitor or an allergic reaction to any factor product were excluded from the clinical trials, so use of the new factor products in these populations has not been examined. One would not expect any issues here either, but clinical experience is needed. Female carriers of hemophilia with low factor activity levels, including pregnant women, were also excluded from the clinical trials. Finally, there are no data on use in patients older than 65 years of age, or for use in previously untreated patients with severe hemophilia. No special problems in any of these populations would be expected, but clinical studies have not been reported.