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Retrospective Study Reflects Successful Transition to Extended Half-Life Therapies

February 13, 2018
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Investigators at the Children’s Hospital of Los Angeles (CHLA) recently published a retrospective review of patient clinical data, the findings of which reflect a series of largely successful transitions to extended half-life (EHL) therapies. The data was drawn from patients treated at CHLA’s Hemostasis and Thrombosis Center (HTC).

“Clinical Use of Recombinant Factor VIII Fc and Recombinant Factor IX Fc in Patients with Hemophilia A and B,” was published February 5, 2018 in the journal Haemophilia. The article’s lead author was Guy Young, MD, Director of the HTC at CHLA. The results were also published as a poster abstract at 59th American Society of Hematology Annual Meeting and Exposition in December 2017.

The study focused on individuals who were previously treated prophylactically with a standard half-life (SHL) factor product, then switched to prophylaxis with an EHL therapy. EHL therapies are designed to keep the infused clotting factor circulating in the body longer, stretching the time between infusions. The EHL products included in the study were a recombinant factor VIII Fc fusion protein (rFVIIIFc) approved for several indications in adults and children with hemophilia A, and a recombinant factor IX Fc fusion protein (rFIXFc) approved for several indications in adults and children with hemophilia B.

While these therapies demonstrated to be both safe and effective in the clinical trials that paved the way for their approval by the U.S. Food and Drug Administration, Young and his colleagues sought corroborating evidence of their effectiveness in an actual clinical setting. They therefore conducted a retrospective review of “real world” clinical data on 36 patients, 17 with hemophilia A and 19 with hemophilia B. 35 of the 36 patients included in the study had a severe form of hemophilia, with one having moderate hemophilia B. Medical records from the HTC database showed that all 36 patients had been previously treated prophylactically with a SHL recombinant FVIII or FIX product and then transitioned to prophylaxis with an EHL therapy.

These patients subsequently experienced a reduction in both annual bleed rate (ABR) and annual joint bleed rate (AJBR). Data culled from the hemophilia A group reflected a mean 232 days of treatment with rFVIIIFc. The switch to an EHL product prompted a drop in ABR from 2.3 to 1.8 and decrease in ABJR from 1.3 to 0.71. Of the 17 patients in this group, eight (47%) experienced zero bleeds during treatment. Data from the hemophilia B group reflected a mean 228 days of treatment with rFIXFc. These patients experienced a fall in ABR from 2.5 to 2.1 and a drop in AJBR from 0.82 to 0.37. Of the 19 patients in this group, twelve (63.1%) experienced zero bleeds during treatment. The authors also reported no significant concerns associated with transitioning, including no reports of inhibitor formation.

The authors acknowledged study limitations that are often inherent in retrospective reviews. These include a scarcity of data related to product transition protocols and lack of pre-established parameters for measuring pharmacokinetics (PK). PKs are important as they indicate the concentration and duration of a drug’s effect in the body and can be used to target factor levels that will help achieve a desired therapeutic response. Despite these study limitations, the authors emphasize the potential advantages of EHL therapies (reduced product consumption, increased adherence rates), provided enhanced PK screening and “future real world studies” for all EHL factor products are utilized.