Altuviiio (efanesoctocog alfa) for hemophilia

Last updated Aug. 22, 2024, by Lindsey Shapiro, PhD
 Fact-checked by Joana Carvalho, PhD

What is Altuviiio for hemophilia?

Altuviiio (efanesoctocog alfa) is an approved long-lasting factor VIII (FVIII) replacement therapy used to reduce the frequency of bleeding episodes or control and manage active bleeds, including those occurring during surgery, in children and adults with hemophilia A.

Previously known as BIVV001, it’s administered via an into-the-vein (intravenous) injection.

It was originally developed by Bioverativ, but the company was acquired in 2018 by Sanofi, which continued Altuviiio’s development in collaboration with Sobi. Sanofi has development and commercialization rights to the therapy in the U.S., while Sobi is responsible for developing and marketing it in Europe and other markets.

Therapy snapshot

How does Altuviiio work?

Hemophilia A patients lack sufficient amounts of FVIII, an important blood clotting protein. Altuviiio is a replacement therapy that’s intended to provide patients with a version of the missing protein.

Similar to some other FVIII replacement therapies, it consists of a lab-made, recombinant version of FVIII that’s fused to a fragment of von Willebrand factor, another clotting protein, that helps stabilize and protect FVIII from degradation.

In addition, Altuviiio contains two other components that help it stay longer in the body. Those are an Fc antibody domain, which prevents FVIII from being degraded inside cells and redirects it back into circulation, and XTEN proteins that shield FVIII from breaking down too early.

Together, these modifications help extend Altuviiio’s half life, or the time it takes for its levels in the body to drop to half of those originally administered. A longer half life means that a compound has a more sustained presence in the bloodstream, and therefore can be administered less frequently when used prophylactically to prevent bleeds. Compared with other standard and extended half-life FVIII products, Altuviiio’s half-life is three to four times higher.

Who can take Altuviiio?

The U.S. Food and Drug Administration (FDA) approved Altuviiio in February 2023 for adults and children with hemophilia A. It’s specifically indicated as a routine prophylactic or preventive therapy to lower the frequency of bleeding episodes. Altuviiio can also be prescribed as an on-demand treatment to control active bleeds, and to manage bleeds during surgery.

Altuviiio is approved for a similar indication in Japan and Taiwan, as well as in the European Union, where it is being marketed under the brand name Altuvoct.

Who should not take Altuviiio?

Altuviiio is contraindicated, or not recommended, for anyone who has had allergic reactions to the medication or any of its ingredients. It’s also not indicated for treating von Willebrand disease, another inherited bleeding disorder.

How is Altuviiio administered?

Altuviiio is delivered as an intravenous injection directly into the bloodstream and may be self-administered after proper training.

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 using. Prefilled 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:

• a yellow cap for 250 IU
• a red cap for 500 IU
• a garnet (dark red) 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 50 IU per kg 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 of 30 or 50 IU/kg every two to three 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 after an interval of at least 72 hours (three full days) from the last on-demand dose.

For surgical management, a single 50 IU/kg dose is recommended before surgery, with additional doses of 30 or 50 IU/kg every two to three days as needed.

A healthcare provider may make dose adjustments based on the patient’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 what’s best in their particular case. Additional instructions for using Altuviiio can be found on the treatment’s website.

Altuviiio in clinical trials

Altuviiio was first found to safely increase FVIII activity with a prolonged half-life relative to other replacement therapies in a small Phase 1/2a trial (NCT03205163) involving men with severe hemophilia A. That prompted the launch of two Phase 3 trials, which ultimately supported its approval in the U.S.

XTEND-1 trial

The open-label Phase 3 XTEND-1 trial (NCT04161495) evaluated Altuviiio in 159 severe hemophilia A patients, ages 12 and older, who’d previously been given other FVIII replacement therapies. Among them, 133 were given Altuviiio on a preventive regimen of 50 IU/kg, delivered intravenously once a week, for a year. The other 26 were given the same 50 IU/kg dose as an on-demand therapy for six months, followed by a six-month preventive regimen.

XTEND-1 met its main goal of effectively keeping bleed rates low among those in the preventive treatment arm, with those patients having a median annualized bleed rate of zero during the study. Nearly two-thirds of those participants had no treated bleeds for the entire year, and a little over half (55.5%) had no bleeds at all. A majority of patients (93%) had fewer than three bleeds, and around 80% didn’t have any spontaneous bleeds, meaning those occurring without an obvious cause.

Among a subgroup of patients who had participated in an earlier observational study while receiving other prophylactic therapies, bleed rates were significantly reduced by 77% with Altuviiio compared with the earlier replacement therapy, declining from a mean of nearly three bleeds a year to 0.69 a year. In that subgroup, measures of life quality, joint health, and pain also favored Altuviiio over previous treatments.

Pharmacological data also showed that 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.

When Altuviiio was given as an on-demand therapy, a single infusion resolved 97% of bleeds. Bleed control was considered excellent by investigators or surgeons for 12 people who underwent major surgery during the study.

XTEND-Kids trial

The Phase 3 XTEND-Kids trial (NCT04759131) tested Altuviiio in 74 boys younger than 12 with severe hemophilia A who’d 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.

Study results showed that none of the enrolled children developed inhibitors, the presence of which could render the treatment less effective, meeting the study’s main goal.

The median annualized rate of bleeds requiring treatment was zero, while the mean annualized bleeding rate was 0.6 for that type of bleed. Nearly two-thirds of children (63.9%) had zero bleeds requiring treatment, and half had no bleeds at all during the study. Spontaneous bleeds requiring treatment were avoided entirely by 87.5% of the children, and 83.3% did not have any treated joint bleeds.

Across 43 bleeds requiring on-demand treatment, 95.3% were resolved with a single 50 IU/kg injection of Altuviiio. When used for surgical management, clinicians always rated bleed control as “excellent.”

The therapy’s safety profile in children participating in this trial was similar to that observed in adults in XTEND-1, with fever being the most common side effect seen in these young patients.

Ongoing trials

The ongoing Phase 3 XTEND-ed extension trial (NCT04644575) is evaluating the long-term safety of Altuviiio in patients who participated in XTEND-1, XTEND-Kids, or any other study of Altuviiio. It also will include severe hemophilia A patients newly initiated on Altuviiio in China and newly started on the treatment for surgical reasons. It’s expected to finish in 2027.

Interim data from XTEND-ed showed the mean annualized bleed rates for adults and adolescents who participated in XTEND-1 and for children younger than 12 who took part in XTEND-Kids were less than one bleed per year.

An observational study (NCT05911763) is also ongoing to assess the real-world safety and effectiveness of Altuviiio, particularly its effects on joint health, in hemophilia A patients in Japan and the U.S. Data will be collected for up to five years. This study is expected to conclude in 2028.

An open-label Phase 3b study called FREEDOM (NCT05817812) is evaluating the effects of weekly Altuviiio treatment on physical activity and joint health among severe hemophilia A patients, ages 12 and older, in Europe. The two-year study is expected to finish in 2026.

Common side effects of Altuviiio

The most common side effects overall associated with Altuviiio include:

• headache
• joint pain.

In clinical trials involving children younger than 12, the most common side effect was fever.

Allergic reactions

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 can 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.

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.