Altuviiio (efanesoctocog alfa) for hemophilia
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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.
The therapy is also being reviewed in the European Union for treating people with hemophilia A of all ages.
Therapy Snapshot
| Brand Name: | Altuviiio |
| Chemical Name: | Efanesoctocog alfa |
| Usage: | Used for preventive or on-demand treatment of bleeds, including those occurring during surgery, in hemophilia A patients |
| Administration: | Intravenous injection |
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, or recombinant version of FVIII and a fragment of von Willebrand Factor, another clotting protein, that helps stabilize and protect FVIII from degradation.
But this recombinant version combines two other components that help it stay longer in the body. The Fc antibody domain prevents FVIII from being degraded inside cells and redirects it back into circulation, while XTEN proteins shield FVIII from breaking down too early.
Together, these three modifications help extend the treatment’s lifespan, enabling Altuviiio to be dosed less frequently when used prophylactically to prevent bleeds.
Indeed, compared with other standard and extended half-life FVIII products, Altuviiio’s half-life is three to four times higher. Half-life is the time it takes for a compound’s concentration in the body to drop to half of its original dose. The longer a compound’s half-life, the longer it will remain in circulation.
Who can take Altuviiio?
The U.S. Food and Drug Administration (FDA) approved Altuviiio in 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.
Who should not take Altuviiio?
Altuviiio is contraindicated, or not recommended, to 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. 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:
- 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 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
Prior to its approval in the U.S., Altuviiio was tested in a series of clinical trials.
EXTEN-A trial
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 adult men with severe hemophilia A, whose FVIII activity levels were less than 1% of normal, received a single dose of Advate (25 IU/kg or 65 IU/kg), another approved FVIII replacement therapy. After a washout period, they all received Altuviiio at the same dose.
Altuviiio safely and effectively increased FVIII activity in trial participants, with a three to four times longer half-life than Advate, meaning it lasted longer in the bloodstream. It also was well tolerated and no allergic reactions or clinically significant side effects were observed.
XTEND-1 trial
The subsequent 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.
Top-line results showed 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’d 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 a year to 0.69 a year.
Measures of quality of life, joint health, and pain also favored Altuviiio over other 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.
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.
XTEND-Kids trial
The Phase 3 XTEND-Kids trial (NCT04759131) tested Altuviiio in 74 boys, up to age 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.
The study’s top-line data showed 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 a year, and a median annual bleeding rate of 0, indicating most were completely free of clinically relevant bleeds.
Additional data showed 64% of the children were bleed-free over the course of treatment. Moreover, more than 80% remained free of joint and spontaneous bleeds. The therapy’s safety profile in children participating in this trial was similar to that observed in adults in XTEND-1.
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 patients newly initiated on Altuviiio in China and newly started on the treatment for surgical reasons. It’s expected to finish in 2027.
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 the U.S. and Japan. Data will be collected for up to five years. This study is expected to conclude in 2028.
Common side effects of Altuviiio
The most common side effects associated with Altuviiio include:
- headache
- joint pain (arthralgia).
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 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.
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.
FAQs about Altuviiio
There are no known interactions between Altuviiio and alcohol. However, because drinking alcohol while yaking certain medications can alter their effectiveness or cause side effects, patients who want to drink alcohol while on Altuviiio should discuss that with their healthcare providers.
By providing hemophilia A patients with a man-made version of factor VIII (FVIII), the blood clotting protein they are missing, Altuviiio should increase FVIII levels and reduce the frequency of bleeds. In the two Phase 3 clinical trials that supported its approval, the therapy significantly reduced the rate of annual bleeds by more than 70% when used as a preventive therapy, and helped resolve more than 90% of bleeds when used on demand.
In the XTEND-1 trial that supported Altuviiio’s approval, a significant reduction in the number of bleeds was observed in patients receiving prophylactic treatment after about one year. Moreover, when used as as on-demand treatment, a single dose of the therapy was sufficient to control 97% of the bleeds that occurred during the study. However, because each person is unique and can respond differently to a medication, patients are advised to talk with their healthcare team about how the therapy may help in their particular case.
In clinical trials, the most common side effects of Altuviiio, reported in more than 10% of the patients, included headache and joint pain. Some patients reported back pain. Patients should ask their healthcare provider about these and other side effects that may be potentially experienced on the therapy.
The U.S. Food and Drug Administration (FDA) approved Altuviiio in 2023 for treating children and adults with hemophilia A. Altuviiio is specifically indicated as a routine prophylactic therapy to lower the frequency of bleeding episodes, as well as an on-demand treatment to control active bleeds, including those occurring during surgery.
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