Rixubis (nonacog gamma) for hemophilia

Last updated March 15, 2024, by Marisa Wexler, MS
Fact-checked by Joana Carvalho, PhD

What is Rixubis for hemophilia?

Rixubis (nonacog gamma) is a replacement therapy approved to prevent and treat bleeds, including those occurring during surgery, in adults and children with hemophilia B.

The therapy, which is administered via an into-the-vein (intravenous) infusion, was originally developed by Baxter International and marketed by its spinoff Baxalta, which is now part of Takeda.

Therapy snapshot

How does Rixubis work?

Hemophilia B is caused by the lack or dysfunction of a clotting protein called factor IX, or FIX. The absence or low activity of this clotting protein leads to impairments in blood clotting, which in turn causes patients to experience the hallmark hemophilia symptoms of excessive and prolonged bleeding.

Rixubis is a factor replacement therapy that contains a functional version of the FIX protein that can be administered to increase FIX activity, helping to promote and restore normal blood clotting in people with hemophilia B.

The therapy specifically contains a recombinant, or lab-made, version of the FIX protein that’s produced using a genetically engineered Chinese hamster ovary cell line.

Who can take Rixubis?

Rixubis was originally approved by the U.S. Food and Drug Administration (FDA) in June 2013 as a routine prophylactic (preventive) therapy to reduce the frequency of bleeds and as on-demand treatment to manage active bleeds, including those occurring around the time of surgery, in adults with hemophilia B. With that decision, Rixubis became the first recombinant FIX product to be approved for hemophilia B in more than 15 years, and the first recombinant factor product to be approved for preventive and on-demand treatment of bleeds in adults with hemophilia B in the U.S.

In September 2014, Rixubis was FDA-approved for children with hemophilia B.

Rixubis is similarly approved in Europe as an on-demand and prophylactic treatment for hemophilia B patients of all ages.

Who should not take Rixubis?

Rixubis is contraindicated, or not recommended, for patients with:

• a known allergy to the therapy or any of its components, including hamster proteins
• disseminated intravascular coagulation, a condition marked by abnormal blood clotting taking place in blood vessels throughout the body
• signs of fibrinolysis, the biological process through which blood clots are broken down.

Rixubis is also not to be used for induction of immune tolerance in hemophilia B patients. This means it should not be used in an attempt to reeducate a patient’s immune system to stop producing neutralizing antibodies (inhibitors) against delivered clotting factors.

How is Rixubis administered?

Rixubis is administered through an infusion directly into the bloodstream. It may be self-administered by patients, but only after they are trained in how to properly do so by a healthcare provider or hemophilia treatment center.

The medication comes as a white powder in single-use color-coded vials of five different strengths:

• Light blue is 250 international units (IU) of FIX.
• Pink is 500 IU of FIX.
• Green is 1,000 IU of FIX.
• Orange is 2,000 IU of FIX.
• Silver is 3,000 IU of FIX.

Before being administered, Rixubis should be reconstituted, or diluted, in sterile water. The therapy should be administered within three hours of being reconstituted at a maximum infusion rate of 10 ml per minute.

When used for routine prophylaxis, the recommended dose of Rixubis for previously treated patients is:

• 60 to 80 IU per kilogram of body weight twice weekly for children younger than 12
• 40 to 60 IU per kilogram of body weight twice weekly for patients 12 and older.

For on-demand treatment, the dosing schedule is determined based on the desired level of FIX activity, which depends on the severity of the bleed:

• For minor bleeds, such as uncomplicated joint bleeds or superficial muscle bleeds, infusions should be given every 12 to 24 hours for at least a day to keep FIX activity levels at 20 to 30 IU/dL until healing is achieved.
• For moderate bleeds, such as muscle bleeds and hematuria (blood in the urine), infusions should be given every 12 to 24 hours for at least two to seven days to keep FIX activity levels at 25 to 50 IU/dL until bleeding is resolved, and healing is achieved.
• For major bleeds, such as those occurring in the brain or abdomen, infusions should be given every 12 to 24 hours for at least seven to 10 days to keep FIX activity levels at 50 to 100 IU/dL until bleeding is resolved, and healing is achieved.

When used to manage bleeds occurring around the time of surgery, Rixubis dosing depends on the type and complexity of the procedure:

• For minor surgical procedures, such as tooth extraction, infusions should be given every 24 hours for at least one day to keep FIX activity levels at 30 to 60 IU/dL until healing is achieved.
• For major surgeries, such as joint replacement surgery or those involving the brain, infusions should be given every eight to 24 hours for at least seven to 10 days to keep FIX activity levels at 80 to 100 IU/dL until bleeding stops, and healing is achieved.

Patients wishing to self-administer Rixubis should follow the specific instructions given by their doctor. Detailed instructions for preparing and administering the therapy are available online.

Rixubis in clinical trials

Rixubis’ original approval for adults with hemophilia B was supported by data from a pivotal Phase 1/3 clinical trial (NCT01174446) that involved 73 previously treated male patients, ages 12-65, with moderately severe or severe hemophilia B (FIX activity levels at 2% or lower than normal).

The therapy’s approval for children was backed by data from a Phase 2/3 clinical trial (NCT01488994) that enrolled 23 children younger than 12 with moderately severe or severe hemophilia B.

Pivotal Phase 1/3 trial

From the 73 patients who were dosed in the pivotal trial, 56 received prophylactic treatment with Rixubis (40 to 60 IU/kg twice weekly) for at least three months, and 14 were given on-demand treatment only.

Among patients treated prophylactically, the overall median annualized bleeding rate was two bleeds per year. Nearly half (42.9%) of the patients were bleed-free over the course of the study, and most did not experience any spontaneous or joint bleeds while they were on Rixubis prophylactic treatment.

Rixubis was also used on demand for 249 bleeding episodes during the trial. Of these, 211 (84.7%) were controlled with one or two infusions of the therapy. Rixubis’ efficacy at controlling bleeds was rated as “good” or “excellent” — meaning that a single dose was enough to provide definite or full relief from pain, and/or ease or halt bleeding — in more than 96% of all treated bleeds.

Pediatric Phase 2/3 trial

In this study, 23 previously treated children younger than 12 received prophylactic treatment with Rixubis (40 to 80 IU/kg twice weekly) for at least three months.

Results showed the median annualized bleeding rate was two bleeds per year, with 39.1.% of patients remaining bleed-free during the study. Most had no spontaneous or joint bleeds.

Rixubis was used on demand for 26 bleeding episodes in the study. From these, 23 (88.5%) were resolved with one or two infusions. The therapy’s efficacy at controlling bleeds was rated as “good” or “excellent” in more than 96% of the cases.

Surgery Phase 3 trial

Rixubis’ safety and efficacy at controlling bleeds occurring around the time of surgery was assessed in a group of 14 previously treated hemophilia B patients, ages 19-54, who participated in a Phase 3 clinical trial (NCT01507896).

The therapy was used to control bleeding in 14 surgeries, including 11 major and three minor surgical procedures. In all cases, the efficacy of the therapy at controlling surgical bleeds during surgery was rated as “excellent.” At the time of hospital discharge, Rixubis’ efficacy at controlling surgical bleeds was rated as “good” or “excellent.”

Common side effects of Rixubis

The most common side effects of Rixubis observed in clinical trials include:

• an altered sense of taste (dysgeusia)
• pain in the extremities
• testing positive for antibodies against a human protein called furin.

Allergic reactions

Allergic reactions, including a severe one called anaphylaxis, may occur in patients given Rixubis. The risk of experiencing an allergic reaction is highest in the initial phases of treatment and in previously untreated patients.

Signs of an allergic reaction may include swelling, chest tightness, low blood pressure, restlessness, nausea, vomiting, tingling, wheezing, or shortness of breath. If patients experience an allergic reaction, Rixubis should be discontinued and appropriate supportive care should be administered promptly.

Rixubis contains small amounts of hamster proteins. Thus, some treated patients may develop allergic reactions against these animal proteins.

Development of inhibitors

In some hemophilia patients given replacement therapies like Rixubis, the body’s immune system may mistake the therapy for an infectious threat. When this happens, neutralizing antibodies called inhibitors are produced. These antibodies target the delivered clotting factor and may prevent it from working as intended. Patients should be tested for the presence of inhibitors if they don’t respond as expected to Rixubis.

Patients who are positive for inhibitors may be at an increased risk of experiencing a severe allergic reaction to Rixubis. For this reason, it’s recommended that patients experiencing an allergic reaction be tested for the presence of inhibitors.

Immune tolerance induction and nephrotic syndrome

There have been reports of nephrotic syndrome, a type of kidney damage, when FIX replacement therapies like Rixubis are used for immune tolerance induction — a type of treatment designed to eliminate inhibitors — in hemophilia B patients with inhibitors.

The safety and effectiveness of Rixubis for immune tolerance induction have not been established.

Blood-clotting complications

The use of FIX-containing products has been associated with thromboembolic, or blood clot-related, complications. Patients on Rixubis should be monitored for the presence of blood-clotting abnormalities, especially those with liver disease, disseminated intravascular coagulation, or other conditions that may predispose them to more blood clots. In patients at risk of experiencing these complications, the benefits and risks of Rixubis treatment should be carefully considered.

Use in pregnancy and breastfeeding

No data are available on the use of Rixubis in people who are pregnant or breastfeeding, and animal studies have not been conducted. Thus, it’s not known if Rixubis can be harmful to a developing fetus, affect female fertility, pass to breast milk, or have a negative effect on breastfed infants.

Patients who are pregnant or breastfeeding, or wish to become pregnant or to breastfeed while taking Rixubis are advised to discuss the potential risks and benefits of treatment with their healthcare providers.

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