Last updated March 10, 2023 by Lindsey Shapiro, PhD
Fact-checked by Joana Carvalho, PhD
What is Altuviiio for hemophilia?
Altuviiio (efanesoctocog alfa), previously known as BIVV001, is an approved long-lasting factor VIII (FVIII) replacement therapy for children and adults with hemophilia A. It is indicated as a prophylactic or preventive therapy to lower the frequency of bleeding episodes, and also can be prescribed as an on-demand treatment for active bleeds. Altuviiio also is indicated for managing bleeds occurring during surgery.
The therapy originally was developed by Bioverativ, which was acquired by Sanofi in 2018. Sanofi continued Altuviiio’s development in collaboration with Sobi. Sanofi will have development and commercialization rights of the therapy in the U.S.
How does Altuviiio work?
Hemophilia A patients lack sufficient amounts of FVIII, an important blood clotting protein. Altuviiio is a replacement therapy that aims to provide patients with a version of the missing protein.
Much like some other FVIII replacement therapies, it consists of a lab-made, or recombinant version of FVIII and a fragment of von Willebrand Factor, another clotting protein. The therapy uses Fc-fusion technology to extend the treatment’s lifespan in the bloodstream and reduce the number of injections needed.
Altuviiio also contains a small protein fragment called XTEN, which ultimately helps to stabilize the therapy and further extend its presence in the bloodstream. In doing so, Altuviiio requires less frequent dosing compared with similar therapies when used prophylactically to prevent bleeds.
Who can take Altuviiio?
The U.S. Food and Drug Administration (FDA) approved Altuviiio in February 2023 for adults and children with hemophilia A.
The therapy is indicated for routine prophylaxis to reduce the frequency of bleeding episodes, on-demand treatment for bleed control, and bleed management during surgery.
Who should not take Altuviiio?
Patients who have experienced allergic reactions to Altuviiio or any of its ingredients should not use the medication. The therapy also is not indicated for the treatment of von Willebrand disease, another inherited bleeding disorder.
How is Altuviiio administered?
Altuviiio is delivered as an into-the-vein (intravenous) injection directly into the bloodstream.
It comes as a white to off-white powder in single-dose vials that must be reconstituted, or diluted, in 3 mL of sterile water within three hours before use. Pre-filled syringes of sterile water are provided.
Vials come in seven different dose strengths based on the international units (IUs) of FVIII activity they provide. Each strength will be listed on the label and the box, and will have a different colored cap. These are as follows:
- a yellow cap for 250 IU
- a red cap for 500 IU
- a garnet cap for 750 IU
- a green cap for 1,000 IU
- a royal blue cap for 2,000 IU
- a mist gray cap for 3,000 IU
- an orange cap for 4,000 IU.
For routine prophylaxis in children and adults, Altuviiio should be administered at a dose of 50 IU per kilogram of body weight once weekly.
For on-demand treatment in children and adults, a single dose of 50 IU/kg is recommended, with additional doses given every 2-3 days as needed. If a minor or moderate bleed occurs within two to three days after a prophylactic dose, a lower on-demand dose of 30 IUs/kg may be used. Prophylactic dosing can be resumed following an interval of at least 72 hours (three full days) from the last on-demand dose.
For surgical management, a single dose of 50 IU/kg is recommended before surgery, with additional doses of 30–50 IU/kg given every 2-3 days as needed.
A patient’s healthcare provider may make dose adjustments based on the person’s response and FVIII activity levels.
Patients should not self-administer Altuviiio until a healthcare provider has shown them how to correctly mix and administer the treatment. Patients who are self-administering Altuviiio should carefully follow their healthcare provider’s instructions regarding the dose and schedule that’s best in their particular case.
Additional instructions for using Altuviiio can be found on the treatment’s website.
Altuviiio in clinical trials
Prior to its approval in the U.S. Altuviiio was tested in a series of clinical trials.
The open-label Phase 1/2a EXTEN-A trial (NCT03205163) investigated the safety, tolerability and pharmacokinetics — a treatment’s movement into, through, and out of the body — of a single dose of Altuviiio.
A total of 16 men with severe hemophilia A whose FVIII activity levels were less than 1% of normal first received a single dose of Advate (25 IU/kg or 65 IU/kg), another approved FVIII replacement therapy. After a three-day washout, all participants received Altuviiio at the same dose.
The results showed that Altuviiio safely and effectively increased FVIII activity in trial participants, with a 3-4 times longer half-life than Advate, meaning it lasted longer in the bloodstream. It also was well tolerated, with no allergic reactions or clinically significant side effects observed.
The subsequent open-label Phase 3 XTEND-1 trial (NCT04161495) evaluated Altuviiio in 159 severe hemophilia A patients, ages 12 and older, who had previously been given other FVIII replacement therapies.
Among them, 133 were given Altuviiio on a preventive regimen of 50 IU/kg, delivered intravenously once per week, for a year. The other 26 participants were given the same 50 IU/kg dose as an on-demand therapy for six months, followed by a six-month preventive regimen.
Top-line results showed that XTEND-1 met its main goal of reducing annualized bleeding rates among those in the preventive treatment arm. Nearly two-thirds of those participants had no bleeds for the entire year, while 93% had fewer than three bleeds. A total of 80% of patients didn’t have any spontaneous bleeds, meaning those occurring without an obvious cause.
For patients who had received other preventive FVIII replacement therapies in a previous study, bleed rates were significantly reduced by 77% with Altuviiio compared with prior therapies, declining from a mean of nearly three bleeds per year to 0.69 per year.
Measures of quality of life, joint health, and pain also favored Altuviiio over other treatments.
Once-weekly Altuviiio could maintain FVIII activity at 40% of normal or higher for about four days after dosing, dropping to 15% of normal by day seven.
For the small group of participants given Altuviiio as an on-demand therapy, a single infusion resolved 97% of bleeds. Bleed control was considered excellent for 12 people who underwent surgery during the study.
The Phase 3 XTEND-Kids trial (NCT04759131) tested Altuviiio in 74 boys, up to age 12, with severe hemophilia A, who had used other FVIII replacement therapies. Its main goal was to assess the development of neutralizing antibodies (inhibitors) against the therapy over a year of weekly treatment.
The study’s top-line data showed that none of the children enrolled in XTEND-Kids developed inhibitors, which render the treatment less effective, meeting the study’s main goal. The children had a mean bleed rate of 0.89 bleeds per year, and a median annual bleeding rate of zero, indicating that most of them were completely free of clinically relevant bleeds.
The ongoing Phase 3 XTEND-ed extension trial (NCT04644575) is evaluating the long-term safety of Altuviiio in patients who participated in XTEND-1 or XTEND-Kids. It also will include patients newly initiated on Altuviiio in China and newly started on the treatment for surgical reasons. It’s expected to finish in 2027.
Common side effects of Altuviiio
The most common side effects associated with Altuviiio include:
- joint pain (arthralgia).
Allergic reactions may occur in patients on Altuviiio, including potentially life-threatening ones known as anaphylaxis. Should patients experience signs of an allergic reaction, such as hives, shortness of breath, chest tightness, wheezing, low blood pressure, or itching, Altuviiio should be discontinued and patients should seek immediate medical care.
Development of inhibitors
Some patients using FVIII replacement therapies may develop inhibitors, or neutralizing antibodies against FVIII that may render treatment less effective. While this is also possible with Altuviiio, inhibitors were not reported in clinical trials.
Patients should be monitored for inhibitor development, particularly if their FVIII levels do not reach what is expected, or if they do not achieve adequate bleeding control.
Use in pregnancy and breastfeeding
There are no data on Altuviiio’s use in pregnant women, and thus, it is not known whether the treatment may cause fetal harm. It’s also not known whether Altuviiio can pass into breast milk, affect milk production, or have any effects on a nursing infant.
Patients who are pregnant, plan to become pregnant, or are nursing or plan to breastfeed should talk with their healthcare team about using this treatment.
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