Low Doses of EHL-FIX Concentrates Can Prevent Bleeds in Severe Hemophilia B, Study Finds

When given at low doses, extended half-life factor IX concentrates Alprolix (eftrenonacog alfa) and Idelvion (albutrepenonacog alfa) can prevent spontaneous bleeds in patients with severe hemophilia B, a study has found.

The study, “A single centre retrospective study of low dose prophylaxis with extended half‐life factor IX for severe haemophilia B,” was published in the journal Haemophilia.

Hemophilia B is a blood clotting disorder caused by the lack of a protein called coagulation factor IX (FIX). Prophylactic (preventive) treatments that provide the missing FIX to patients with hemophilia B are currently the gold standards to prevent spontaneous bleeding episodes.

Standard half-life FIX (SHL-FIX) concentrates have, as their name suggests, a short half-life, meaning it takes a small amount of time for their levels to drop to half after being administered. For that reason, and to maintain the levels of FIX in the blood within a normal range, these medications must be administered every two to three days.

In 2016, the first extended half-life factor IX (EHL-FIX) concentrates were introduced in the U.K. These treatments have a longer half-life than SHL-FIX, and only need to be administered once every week or every other week to be effective.

Previous clinical trials assessing the efficacy of two EHL-FIX concentrates — Sanofi‘s Alprolix (NCT01027364) and CSL Behring’s Idelvion (NCT0101496274) — showed both compounds were able to prevent spontaneous bleeds in patients with severe hemophilia B when administered at a dose of 40–50 IU/kg, once a week.

“These higher doses that were used in the trials do not reflect everyday clinical practice as they far exceed what is used clinically in the U.K., which is approximately 15 IU/kg for Idelvion and 30 IU/kg for Alprolix,” the researchers wrote.

To assess the safety and efficacy of both EHL-FIX concentrates when given at lower doses, the researchers collected and analyzed real-world data from 20 patients with severe hemophilia B who switched from SHL-FIX concentrates to either Alprolix or Idelvion.

All patients were being followed at the Oxford Haemophilia & Thrombosis Centre between January 2016 and June 2019. Data was collected one year before and one year after the switch, and included the number of bleeding events per year, the lowest level of FIX in the blood, the frequency of dosing, and quality of life.

The lowest level of FIX in the blood following treatment administration, also known as trough level, is clinically important to determine when a new dose of the medication needs to be administered.

From the 20 patients included in the study, 13 switched from SHL-FIX concentrates to Alprolix (mean dose of 31.5 IU/kg), and the remaining seven switched to Idelvion (mean dose of 20.2 IU/kg).

No significant differences were found in the annual number of bleeding events that the patients experienced while receiving SHL-FIX or EHL-FIX concentrates (median of three episodes per year on both treatments).

Likewise, no significant differences were found in patients’ FIX trough levels while being treated with either concentrates. However, dosing frequency was reduced by 52% following the switch to EHL-FIX concentrates, with an average of one dose per week instead of one every three days with SHL-FIX.

Finally, patients reported no significant changes in quality of life before and after the switch, indicating that EHL-FIX concentrates do not hinder nor improve patient’s quality of life compared to SHL-FIX compounds.

“These data suggest that [annual bleeding rate], trough levels, and QoL [quality of life] measures are similar between SHL-IX and EHL-IX treatments given at low doses,” the researchers wrote. “However, these treatments need to be optimized further to achieve better outcomes and ideally zero bleeding episodes. Longer follow-up will provide more meaningful comparisons for all outcomes, in particular for QoL.”

Three patients receiving Idelvion decided to switch back to SHL-FIX concentrates after experiencing spontaneous bleeding events. Furthermore, one patient receiving Alprolix developed an allergic reaction and was forced to switch back to SHL-FIX concentrates.

Treatment with EHL-FIX concentrates is safe and as effective as SHL-FIX compounds for hemophilia B patients, while providing a clear advantage in dosing frequency and overall cost, the researchers said. However, they noted the small number of patients included in the analysis might be a potential source of bias in the study.

“This study has shown that EHL‐IX can be considered a safe and effective treatment for [hemophilia B] when using real‐world dosing regimens, but more real‐life data are needed to determine any difference between Alprolix and Idelvion, while adjusting the dosing could be helpful in reducing bleeding rates further,” they wrote.