First Child with Hemophilia B Dosed in Phase 4 Trial to Extend Ixinity to Those Under Age 12

Aptevo Therapeutics announced the dosing of a first patient in a Phase 4 study aiming to extend use of its prophylactic (preventive) treatment Ixinity (coagulation factor IX [recombinant]) to children with hemophilia B  younger than 12 years old.

“Initiation of the clinical study of Ixinity in younger patients is the next step in expanding treatment options for patients with hemophilia B,” Mike Adelman, senior vice president of commercial operations at Aptevo, said in a press release.

About one-third (34%) of hemophilia B patients in the U.S. are thought to be under age 12, according to an estimate given by the World Federation of Hemophilia in a 2017 report. A pediatric label extension could significantly increase those able to be treated with Ixinity.

Hemophilia B is caused by a deficiency in the blood clotting factor IX (FIX). Ixinity is a replacement therapy that contains recombinant (lab-made) coagulation factor IX. It is given directly into the vein (intravenous) of patients to replenish FIX levels, and restore the normal blood clotting process.

Ixinity is currently approved for use in the U.S. by hemophilia B patients ages 12 and older to control or prevent bleeding episodes, and to manage blood loss during surgery.

“This study, together with the introduction of a 3000 IU range vial last year, reinforces that Aptevo is continuing to execute on new initiatives that will support further growth of Ixinity,” Adelman said.

Aptevo presented positive results obtained in a small group of pediatric patients at a 2017 scientific conference. Pooled data from two trials — including the Phase 3 study (NCT01271868) — covered 12 hemophilia B patients under age 12, and showed that prophylaxis or on-demand treatment with Ixinity was safe and well-tolerated in children.

Of a total of 61 bleeding episodes experienced by these children, six (10%) resolved with no use of Ixinity, 44 (72%) resolved after one infusion, five (8%) required two infusions, and six (10%) required three to five infusions of Ixinity. Bleed control was rated as excellent in 65% of bleeding episodes, good in 32%, and fair in 3%.

The most common side effect was hyperhidrosis (excessive sweating), and one patient ran a fever. No one developed factor IX inhibitors (antibodies that render the treatment ineffective) during the study.

Overall, Ixinity efficacy for controlling bleedings in children was comparable to that demonstrated in the pivotal Phase 3 trial (NCT00768287) an overall patient population, which formed the basis for the treatment’s approval in the U.S. This study included both children and adults.

The ongoing and open-label Phase 4 trial (NCT03855280) will evaluate the safety, efficacy, and pharmacokinetics (distribution and availability in the body) of prophylactic treatment with Ixinity in 22 previously treated children under 12 years of age with moderate to severe hemophilia B.

The study is designed to gather information on two age groups, those under 6 years old and those ages 6 to 12.

It will consist of three distinct parts. Initially, patients will receive a single dose of Ixinity, followed by factor IX activity and safety assessments to determine how long the treatment stays active in the blood.

Next, patients will be started on Ixinity prophylaxis, dosed based on prior tests and ideally ranging between 35 to 75 international unit (IU)/kg twice weekly, during 50 exposure days (about six months).

After this period, children may continue with the treatment for 50 or more exposure days.

The trial is currently recruiting patients in Moldova and Ukraine. Enrollment is also expected to open at a site in South Africa. More information is available here.

“We are very encouraged by the pediatric subset data from the Phase 3 Ixinity program and are excited to begin this latest study,” Adelman said.

“We look forward to completing this current study and pursuing potential future licensure of Ixinity for the approximately one-third of hemophilia B patients in the U.S who are not included in our present label.”