Outcome of Clinical Trials with New Extended Half-Life FVIII/IX Concentrates

Abstract

The development of a new generation of coagulation factors with improved pharmacokinetic profile will change the paradigm of treatment of persons with hemophilia (PWH). The standard treatment in PWH is represented by regular long-term prophylaxis that, given intravenously twice or thrice weekly, is associated with a not-negligible burden on patients’ quality of life. The availability of drugs with improved pharmacokinetic profile may improve prophylaxis feasibility and protection against bleeding episodes. This article summarizes the main results obtained from clinical trials with modified factor VIII (FVIII) and factor IX (FIX) molecules. Published literature on new molecules for replacement treatment in hemophilia A and B was retrieved using PubMed search, and all ongoing clinical trials have been researched via . Such new molecules are usually engineered to have a longer plasma half-life than that which has been obtained by chemical modification (i.e., conjugation with polyethylene glycol, PEG) or by creating recombinant fusion proteins. Results from phase I/III studies in previously treated adults and children are now available for the vast majority of new products, including the results of their use in a surgical setting. On the contrary, trials involving previously untreated patients are still ongoing for all and results not yet available.

Extended half‐life rFIX in major surgery—How to improve clinical practice: An intraindividual comparison

“…Like all invasive procedure in this kind of patients, orthopedic surgery requires prophylactic administration of the missing factor both at preoperative and postoperative level. Recently, extended half‐life (EHL) concentrates for hemophilia A and B are being introduced in the prophylaxis and treatment of bleeding . Nevertheless, their use is still limited and surgery guidelines are quite conservative and suggest caution .…”

“…Recently, extended half-life (EHL) concentrates for hemophilia A and B are being introduced in the prophylaxis and treatment of bleeding. 6 Nevertheless, their use is still limited and surgery guidelines are quite conservative and suggest caution. 7 In this regard, various relevant issues are under debate, such as cost-effective treatment and cost-saving pharmacokinetic (PK) approach.…”

PEGylated biologics in haemophilia treatment: Current understanding of their long‐term safety

“…Improved pharmacokinetics (PK) and pharmacodynamics con- Table 1). 3 The resulting half-life prolongation is substantially higher for FIX compared with FVIII products.…”

Choices of factor VIII products in previously untreated patients with haemophilia A: A global survey

“…[1][2][3][4][5][6] A reason that may prompt to consider to switch these patients to rFVIII is the current availability of products of this class that, in comparison with those of first through third generations evaluated in SIPPET, are endowed with an extended plasma half-life (EHL) that allows to reduce by 20%-30% the number of yearly intravenous injections and thus improve patients' quality of life. 7 Another reason that may lead to choose rFVIII after the period of high inhibitor risk has elapsed is the perception that these products may be safer than those derived from human plasma, concerning the transmission bloodborne infectious agents that might escape the current robust methods of viral inactivation and removal.…”