Idelvion (albutrepenonacog alfa) for hemophilia

Last updated Oct. 11, 2023, by Lindsey Shapiro, PhD
Fact-checked by Joana Carvalho, PhD

What is Idelvion for hemophilia?

Idelvion (albutrepenonacog alfa) is an approved factor IX (FIX) replacement therapy for the prevention and treatment of bleeds, including those occurring during surgery, in adults and children with hemophilia B.

The therapy, developed and marketed by CSL Behring, is administered via an intravenous, or into-the-vein, injection.

Therapy snapshot

How does Idelvion work?

Due to mutations in the F9 gene, hemophilia B patients lack an important blood clotting protein known as factor IX, or FIX, which leads to a propensity to excessive and prolonged bleeding.

Idelvion contains a recombinant, or lab-made, version of FIX that’s intended to restore the levels of the missing clotting protein, so as to prevent or control bleeds in hemophilia B patients.

The FIX protein that’s found in Idelvion is fused to albumin — a protein naturally found in the blood that’s highly stable and is known to remain in circulation for long periods of time. This specific modification, referred to as albumin fusion, helps to prevent FIX from being degraded, prolonging the therapy’s presence in the bloodstream relative to standard FIX replacement therapies. Idelvion therefore is considered to be an extended half-life (EHL) therapy.

When blood clotting is initiated, albumin is cleaved off and active FIX is released to control bleeding.

Who can take Idelvion?

The U.S. Food and Drug Administration (FDA) approved Idelvion in March 2016 for children and adults with hemophilia B. That decision made Idelvion the first albumin fusion clotting factor product to be approved in the U.S.

The therapy can be used for routine bleed prevention, or prophylaxis, as well as for bleed prevention around the time of surgery — known as perioperative bleed management. It also can be used to control active bleeds as an on-demand treatment.

Idelvion is similarly authorized in the European Union, in Japan, and in other areas worldwide.

Who should not take Idelvion?

Idelvion is contraindicated, or not recommended, for patients who have had life-threatening allergic reactions to the medication or any of its ingredients, including hamster proteins.

The therapy also is not indicated for induction of immune tolerance in hemophilia B patients. Immune tolerance is a type of treatment that aims to re-educate a patient’s immune system to cease producing neutralizing antibodies, or inhibitors, against delivered clotting factors.

How is Idelvion administered?

Idelvion is given via an intravenous injection and may be self-administered or given by a caregiver after proper training and approval by a healthcare provider or hemophilia treatment center.

The medication comes as a pale yellow to white powder in single-use vials containing varying doses of FIX. It must be dissolved in sterile water before being infused within a period of four hours.

The vials are labeled with their dose strength and are color coded:

• orange, for the dose of 250 international units (IU) of FIX
• blue, for a 500 IU dose
• green, for a dose of 1,000 IU
• purple, for a 2,000 IU dose
• yellow, for a 3,500 IU dose.

The recommended dose of Idelvion depends on whether it is being used as a preventive or on-demand therapy, as well as on other clinical factors. The rate of administration should be determined by the patient’s comfort level, up to a maximum of 10 mL per minute.

For routine prophylaxis, the recommended dose of Idelvion for patients ages 12 and older is 25-40 IU per kilogram of body weight once weekly. Patients may be switched to 50-75 IU/kg every two weeks if bleeds are well controlled. In Europe, a dosing regimen of once every three weeks also has been approved.

For patients younger than 12, the recommended dose of Idelvion for prophylaxis is 40-55 IU/kg once weekly. The therapy’s prophylactic regimen may be further adjusted to each patient’s individual needs based on the clinical response.

For on-demand treatment and perioperative management, the dose and duration of treatment depends on the severity of FIX deficiency, the location and extent of bleeding, the patient’s clinical condition, age, and FIX recovery rate.

Idelvion’s dose will be determined by a healthcare provider based on a person’s body weight and desired FIX increase, with adjustments based on clinical condition and response.

For on-demand treatment, the dose of Idelvion is calculated based on the severity of the bleed.

• For minor and moderate bleeds, such as uncomplicated joint, muscle, or oral bleeds, Idelvion should be given every 48 to 72 hours to maintain FIX activity levels at 30%-60% for at least one day until bleeding stops and healing is achieved. A single dose of the medication should be sufficient to control most of these bleeds.
• For major bleeds, such as deep muscle bleeds or those that are life-threatening or occurring in the brain, Idelvion should be given every 48 to 72 hours to maintain FIX activity levels at 60%-100% for 7-14 days until bleeding is resolved and healing is achieved. A weekly maintenance dose is recommended in such cases.

When used for perioperative management, the dose of Idelvion is adjusted based on the scale of the surgery.

In patients undergoing minor surgery, such as an uncomplicated tooth extraction, Idelvion should be given every 48 to 72 hours to maintain FIX activity levels at 50%-80% for at least one day, or until healing is achieved. According to the therapy’s prescribing information, a single dose of Idelvion should be sufficient to control bleeds associated with the majority of minor surgeries.

In patients undergoing major surgeries, such as those involving the brain, Idelvion should be given every 48 to 72 hours to maintain FIX activity levels at 60%-100% for 7-14 days, or until bleeding stops and wound healing is complete. A once- or twice-weekly maintenance dose is recommended in such cases.

Patients may be trained to self-administer Idelvion; caregivers also may be taught to give the medication. Anyone self-administering Idelvion should carefully follow clinician instructions. In case of doubt, patients should contact their healthcare provider before using the medication.

Idelvion in clinical trials

Idelvion’s approvals were backed by data from a large clinical development program called PROLONG-9FP.

After Phase 1 trials showed the therapy was safe and had a prolonged presence in the bloodstream, Idelvion was tested in two Phase 3 trials involving previously treated adults/adolescents and children with hemophilia B.

Phase 3 trials

A multinational, open-label Phase 2/3 trial (NCT01496274) evaluated Idelvion as a preventive and on-demand treatment in 63 previously treated adults and adolescents, ages 12 to 61, with moderate to severe hemophilia B. Participants were treated for up to 27 months, or a little longer than two years, with either weekly or biweekly dosing.

The results showed that the median rate of spontaneous bleeds or joint bleeds among patients on either regimen who had continuously been on preventive treatment with Idelvion was zero. For 19 patients who switched from on-demand treatment to a preventive regimen, bleed rates were significantly reduced after that change.

Overall, about 94% of bleeding episodes were successfully treated with a single injection of Idelvion. Efficacy at controlling bleeds was rated as excellent or good in more than 90% of the cases.

Another Phase 3 trial (NCT01662531) evaluated the therapy in 27 children, ages 11 or younger, with moderate to severe disease. Patients were treated once weekly for as long as 1.5 years.

The median spontaneous bleed rate was zero in these young patients, with about 89% of bleeding episodes being successfully managed with one injection. Bleed control was rated as excellent or good for 96% of the treated bleeding episodes. The therapy had a similar safety profile in these young patients as it did in adults.

An extension study (NCT02053792) then examined the long-term safety and efficacy of Idelvion in participants from either of the two clinical trials, as well as in patients who had not previously received FIX products.

For both the adults and adolescents continuing treatment from the previous studies, the median spontaneous and joint bleed rates remained low, with comparable efficacy between weekly and biweekly dosing regimens, the results showed. Overall, more than 95% of bleeds were successfully treated with one or two Idelvion injections.

Surgical substudy

PROLONG-9FP also included a surgical substudy that evaluated the efficacy of Idelvion at managing bleeds occurring around the time of an operation. Among the 21 patients who received perioperative treatment for 30 surgeries, bleed control was rated as excellent or good in 93% of the procedures, with only one preoperative dose of Idelvion needed to maintain bleed control in 97% of the cases.

Ongoing trials

CSL Behring is sponsoring a non-interventional study called OrPHEe (NCT05086575) to record data related to the real-world use of Idelvion among people with hemophilia B in France. Launched in 2021 and involving up to 100 patients, the study is expected to finish in 2026.

Common side effects of Idelvion

The most common side effects reported in clinical trials of Idelvion include:

• headache
• dizziness
• allergic reactions (hypersensitivity)
• rash.

Allergic reactions

Hypersensitivity reactions have been reported in patients using Idelvion. The medication contains trace amounts of Chinese hamster ovary proteins, which can lead to such reactions.

Patients should stop using Idelvion and contact their doctor if they experience any early symptoms of an allergic reaction. These symptoms may include rash, hives, itching, tightness in the chest or throat, difficulty breathing, lightheadedness, dizziness, nausea, or a drop in blood pressure.

Development of inhibitors

As with other replacement therapies, patients using Idelvion may develop inhibitors, or neutralizing antibodies against FIX that can make the therapy less effective. All patients on Idelvion should be monitored for the possible development of inhibitors, particularly those who do not achieve the expected FIX activity levels in the bloodstream with treatment, or in whom bleed control is inadequate.

Patients with FIX inhibitors are thought to be at an increased risk of experiencing serious allergic reactions when exposed to FIX products like Idelvion. For that reason, it’s recommended that patients experiencing an allergic reaction be evaluated for the presence of inhibitors. Those with inhibitors should be closely monitored for potential signs and symptoms of an acute allergic reaction, especially in the initial phases of treatment.

Blood clotting complications

Idelvion may increase the risk of certain blood clotting complications, particularly in patients with certain risk factors, such as liver disease, a recent history of surgery, or a higher tendency of making blood clots. Patients should call their healthcare provider if they experience potential symptoms of a blood clotting problem, including chest pain, difficulty breathing, leg tenderness, or swelling.

Immune induction and nephrotic syndrome

Idelvion is not indicated for immune tolerance induction, which is a form of treatment sometimes used to help eliminate inhibitors in people who develop these neutralizing antibodies. There have been reports of nephrotic syndrome, a condition characterized by kidney damage, developing after attempted immune tolerance induction with FIX products like Idelvion in people who have inhibitors and a history of allergic reaction to these therapies. The safety and efficacy of Idelvion for inducing immune tolerance have not been established.

Use in pregnancy and breastfeeding

It is not known whether Idelvion is safe to use during pregnancy or while breastfeeding. Additionally, no animal studies have evaluated the therapy’s effects on reproduction or fetal development, so it is unclear whether Idelvion can affect reproduction or cause harm to a developing fetus.

Patients should talk about these issues with their doctor if they become or plan to become pregnant, or breastfeed while receiving treatment.

Hemophilia News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.