Treatment and prevention of bleeds in children and adults with hemophilia B
How does Ixinity work?
Hemophilia B is a bleeding disorder caused by a deficiency of one of the factors required for blood clotting — specifically, factor IX, known as FIX. As a result, blood clotting is delayed and patients may experience excessive and prolonged bleeding.
Ixinity is a lab-made version of human FIX designed to restore factor IX levels and allow normal blood clotting in hemophilia B patients.
The treatment is used on demand to control active bleeds, but also may be taken as a preventive (prophylactic) therapy to reduce the frequency of bleeding episodes. Ixinity also may be used to manage blood loss during surgery.
Who can take Ixinity?
The U.S. Food and Drug Administration (FDA) approved Ixinity in 2015 to treat on-demand bleeds, and for surgery management, in adults and children, 12 years of age or older, with hemophilia B. Later, the therapy was approved as a prophylactic treatment for adults and children of the same ages with hemophilia B.
Now, the FDA is reviewing an application from Medexus seeking to expand Ixinity’s approval to include children younger than 12.
Who should not take Ixinity?
According to the therapy’s prescribing information, patients with a known sensitivity to Ixinity or any of its ingredients, including hamster proteins, should not use Ixinity.
The therapy also is not indicated for induction of immune tolerance — a treatment to re-educate a patient’s immune system to cease the production of neutralizing antibodies (inhibitors) against delivered clotting factors — in hemophilia B patients.
How is Ixinity administered?
The therapy comes as a white powder in single-use glass vials containing 250, 500, 1,000, 1,500, 2,000, or 3,000 international units (IU) of FIX. It should be reconstituted, or diluted, in sterile water and administered as an intravenous infusion.
Ixinity may be given by a healthcare provider or self-administered at home after proper training and instruction. Patients should never self-administer Ixinity unless they have been taught how to safely do so by a healthcare professional.
The appropriate dose and frequency of Ixinity treatment will be determined by a clinician based on the patient’s age, body weight, and clinical condition, as well as the type of bleed, bleeding severity, and degree of FIX deficiency.
As a prophylactic, Ixinity is typically administered at a dose of 40-70 IU per kilogram of body weight twice weekly; that dosage may be adjusted based on the factors described above.
For on-demand treatment, Ixinity is recommended to be given at varying doses, depending on bleed severity, to maintain FIX activity levels. These dosages are given until healing is achieved:
30 to 60 IU/dL, with dosing every 24 hours for 1-3 days, in the case of minor bleeds
40 to 60 IU/dL, with dosing every 24 hours for 2-7 days, in the case of moderate bleeds
60 to 100 IU/dL, with dosing every 12-24 hours for 2-14 days, in the case of major or life-threatening bleeds.
For minor surgical procedures, the therapy should be given every 24 hours for 1-5 days after surgery to maintain FIX activity levels at 30 to 80 IU/dL. Before surgery, the medication should be given to ensure FIX activity levels are at 50 to 80 IU/dL.
For major surgical procedures, Ixinity should be given every 8-24 hours after surgery to maintain FIX activity levels at 40 to 60 IU/dL in the first three days. On days 4-6, it should be given at 30 to 50 IU/dL, and then administered at 20 to 40 IU/dL from day seven to day 14. Before surgery, the medication should be given to ensure FIX activity levels are at 60 to 80 IU/dL.
Ixinity in clinical trials
Ixinity was approved for use in hemophilia B, for adults and children 12 years of age and older, based on the results of clinical trials. The therapy also is being tested in younger patients.
For adults and children ages 12 and older
A multicenter Phase 2/3 trial (NCT00768287) assessed Ixinity’s safety, efficacy, and pharmacokinetics — its movement into, through, and out of the body — in 77 hemophilia B patients with severe or moderately severe disease. All had previously been treated with FIX replacement therapy.
The study’s first randomized, controlled part compared the pharmacokinetics of Ixinity against BeneFix (nonacog alfa), another FIX replacement therapy. It found that the pharmacokinetics were comparable between the two treatments.
A second, open-label part evaluated Ixinity’s safety and effectiveness at controlling or preventing bleeds. The results showed that Ixinity was well tolerated. The most common side effect was headache. There were no reports of FIX inhibitors during treatment.
Ixinity was effective at preventing bleeds (prophylaxis treatment), with a median annual bleed rate of 1.52. It also effectively controlled bleeds, with one or two infusions able to resolve 84% of bleeds. Participants usually rated the treatment’s ability to control bleeds as excellent or good, and trial investigators deemed the treatment effective in more than 90% of cases.
Findings from a trial sub-study demonstrated that the treatment also was beneficial for surgical management. Surgeons rated Ixinity as adequate or better than adequate at controlling bleeds during 19 major surgeries.
For children younger than 12
An analysis of pooled data from two studies showed that Ixinity also was safe and well-tolerated in 12 children younger than age 12. The treatment also showed comparable efficacy to that shown in the earlier trial involving older patients.
Of 61 total bleeding episodes, six (10%) resolved with no infusions of Ixinity, and 44 (72%) resolved after one infusion. Five bleeding episodes (8%) required two infusions, and six (10%) required 3-5 infusions.
Participants rated bleed control as excellent in 65% of the bleeds, good in 32%, and fair in 3%. The most common side effect was excessive sweating, reported in two patients.
A Phase 3/4 trial (NCT03855280) tested Ixinity among 21 children, all younger than age 12, with moderate to severe hemophilia B. After an initial part to test the safety of a single dose, patients received twice weekly preventive treatment with Ixinity.
The mean annual bleeding rate on Ixinity was 2.34 bleeds per year, with a mean spontaneous bleed rate of 0.63 per year, the results showed. Seven children had no bleeds throughout the trial. Most bleeds that occurred during the study (83.8%) resolved after one or two infusions of Ixinity.
Ixinity’s efficacy for bleed control was rated as excellent or good by participants in 78.8% of cases; it was deemed effective by all investigators.
No clinically meaningful differences were observed between children younger than 6 or those age 6 and older. The therapy was generally well tolerated in these young patients.
Common side effects of Ixinity
The most common side effect of Ixinity reported in clinical trials was headache.
Allergic reactions, including anaphylaxis — a severe and life-threatening allergic reaction — have been reported in patients using Ixinity. Signs of an allergic reaction may include swelling, hives, chest or throat tightness, low blood pressure, lethargy, nausea, vomiting, difficulty swallowing, abnormal sensations, wheezing, or difficulty breathing.
Patients experiencing signs of an allergic reaction should seek medical care immediately.
Some patients also may develop neutralizing antibodies, or inhibitors, against the treatment. This can reduce the medication’s effectiveness and make allergic reactions more likely. If expected FIX levels are not attained or bleeding is not controlled with Ixinity, it is recommended that a blood test for inhibitors should be performed.
Ixinity may cause nephrotic syndrome, a condition in which the body passes too much protein in the urine, usually as a result of kidney damage. Nephrotic syndrome is more likely in patients with a history of allergic reactions or inhibitor development.
Blood clots (thromboembolism) may occur when using Ixinity. Patients should be monitored for blood clots during treatment, with close observation given those with liver disease, individuals who have undergone surgery, and those at an increased risk of clotting events.
Pregnancy and breastfeeding
No clinical or preclinical data exist regarding the use of Ixinity in pregnant patients or while breastfeeding. Individuals with hemophilia B who are pregnant or wish to become pregnant when using Ixinity should discuss this with their healthcare team.
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