Bridgewater, N.J., September 12, 2023. The U.S. Food and Drug Administration (FDA) has accepted a supplemental biologics license application (sBLA) for ALTUVIIIO® [Antihemophilic Factor (Recombinant), Fc-VWF-XTEN Fusion Protein-ehtl]. The sBLA is based on positive final results from the pivotal Phase 3 XTEND-Kids study, which demonstrated highly effective bleed protection in children with severe hemophilia A with once-weekly dosing. The Prescription Drug User Fee Act (PDUFA) action date is May 10, 2024.
ALTUVIIIO is a first-in-class, high-sustained factor VIII replacement therapy that is indicated for use in adults and children with hemophilia A for routine prophylaxis and on-demand treatment to control bleeding episodes as well as perioperative management (surgery).
The FDA approval in February 2023 was supported by interim data from XTEND-Kids, an open-label, non-randomized interventional study evaluating the safety, efficacy, and pharmacokinetics of ALTUVIIIO as once-weekly prophylaxis in previously treated children under 12 years old with severe hemophilia A. While the current label already includes use of ALTUVIIIO in adults and children, the sBLA seeks to update the Prescribing Information with the final Phase 3 XTEND-Kids study results, which were presented at a late-breaker session at the Annual Meeting of the International Society on Thrombosis and Haemostasis (ISTH) in Montreal, Canada.
Jeff Schaffnit
Head of U.S. Rare Blood Disorders at Sanofi
“In the U.S., treatment advances over time have given children living with hemophilia the opportunity to move from watching sports as a spectator to becoming an active participant with certain limitations and considerations. With ALTUVIIIO, we are building on this momentum by offering a first-of-its-kind option with proven bleed protection and reduced treatment burden for healthcare providers and caregivers of children with hemophilia A.”
Hemophilia A is a rare, lifelong condition in which the ability of a person’s blood to clot properly is impaired, leading to excessive bleeds and spontaneous bleeds into joints that can result in joint damage and chronic pain, and potentially impact quality of life. Hemophilia is typically diagnosed at a very young age and the severity is determined by the level of clotting factor activity in a person’s blood, meaning there is a negative correlation between bleeding risk and factor activity levels.
XTEND-Kids Results Reaffirm ALTUVIIIO’s Therapeutic Benefit
Children with hemophilia typically clear administered factor concentrates in the blood at a higher rate than adults, so multiple injections per week are often needed when using other factor replacement products. Full results from XTEND-Kids reinforce that a once-weekly 50 IU/kg dose of ALTUVIIIO provides highly effective bleed protection in children with hemophilia A and the medicine can be used across clinical scenarios.
In the XTEND-Kids study, patients (n=74) received once-weekly ALTUVIIIO prophylaxis (50 IU/kg) for 52 weeks. ALTUVIIIO met the study’s primary endpoint with no factor VIII inhibitor development detected (0% [95% confidence interval (CI)] 0–4.9]). ALTUVIIIO also met key secondary endpoints with median (interquartile range [IQR]) and mean (95% CI) annualized bleeding rates (ABR) of 0.00 (0.00–1.02) and 0.89 (0.56–1.42), respectively, as well as maintenance of factor activity levels in the normal to near-normal range (above 40%) for approximately three days. ALTUVIIIO demonstrated a safety profile similar to the XTEND-1 trial, confirming efficacy in both adults and children. No serious allergic reactions, anaphylaxis, or embolic or thrombotic events were reported. Although none were reported in the clinical study, formation of inhibitors and allergic reactions are possible when taking ALTUVIIIO. The most common treatment-emergent adverse events (>10%) were SARS-CoV-2 test positive, upper respiratory tract infection, and fever (pyrexia). No adverse events led to treatment discontinuation.
Granted Breakthrough Therapy designation by the FDA in May 2022 — the first factor VIII therapy to receive this designation — ALTUVIIIO also received Fast Track designation in February 2021 and Orphan Drug designation in 2017. The European Commission granted Orphan Drug designation in June 2019.
About ALTUVIIIO®
ALTUVIIIO [Antihemophilic Factor (Recombinant), Fc-VWF-XTEN Fusion Protein-ehtl] is a first-in-class high-sustained factor VIII therapy that is designed to extend protection from bleeds with once-weekly prophylactic dosing for adults and children with hemophilia A. In adults and adolescents, ALTUVIIIO has a 3 to 4-fold longer half-life relative to standard and extended half-life factor VIII products. Once-weekly treatment with ALTUVIIIO provides high-sustained factor activity levels within the normal to near-normal range for most of the week in adults and for approximately three days in children. ALTUVIIIO is the first factor VIII therapy that has been shown to break through the von Willebrand factor ceiling, which imposes a half-life limitation on other factor VIII therapies. ALTUVIIIO builds on the innovative Fc fusion technology by adding a region of von Willebrand factor and XTEN polypeptides to extend its time in circulation.
About the XTEND Clinical Programs
The XTEND clinical program is comprised of two Phase 3 trials in hemophilia A: XTEND-1 in people 12 years or older and XTEND-Kids in children younger than 12 years old. There is also an ongoing extension study (XTEND-ed).
The Phase 3 XTEND-1 study (NCT04161495) was an open-label, non-randomized interventional study assessing the safety, efficacy, and pharmacokinetics of once-weekly ALTUVIIIO in people 12 years of age or older (n=159) with severe hemophilia A who were previously treated with factor VIII replacement therapy. The study consisted of two parallel treatment arms — the prophylaxis Arm A (n=133), in which patients who had received prior factor VIII prophylaxis were treated with once-weekly intravenous ALTUVIIIO prophylaxis (50 IU/kg) for 52 weeks, and the on-demand Arm B (n=26), in which patients who had received prior on-demand factor VIII therapy began with 26 weeks of on-demand ALTUVIIIO (50 IU/kg), then switched to once-weekly prophylaxis with ALTUVIIIO (50 IU/kg) for an additional 26 weeks.
The primary efficacy endpoint of XTEND-1 was the mean annualized bleeding rate (ABR) in Arm A, and the key secondary endpoint was an intra-patient comparison of ABR during the ALTUVIIIO weekly prophylaxis treatment period versus the prior factor VIII prophylaxis ABR for a subset of participants in Arm A who had participated in a previous observational study (Study 242HA201/OBS16221).
The XTEND-Kids study (NCT04759131) was an open-label, non-randomized interventional study of the safety, efficacy, and pharmacokinetics of once-weekly ALTUVIIIO in previously treated patients younger than 12 years of age with severe hemophilia A. Patients received once-weekly ALTUVIIIO prophylaxis (50 IU/kg) for 52 weeks. The primary endpoint was the occurrence of inhibitor development.
U.S. INDICATIONS AND IMPORTANT SAFETY INFORMATION
INDICATION
ALTUVIIIO™ [antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl] is an injectable medicine that is used to control and reduce the number of bleeding episodes in people with hemophilia A (congenital Factor VIII deficiency).
Your healthcare provider may give you ALTUVIIIO when you have surgery.
IMPORTANT SAFETY INFORMATION
What is the most important information I need to know about ALTUVIIIO?
Do not attempt to give yourself an injection unless you have been taught how by your healthcare provider or hemophilia center. You must carefully follow your healthcare provider's instructions regarding the dose and schedule for injecting ALTUVIIIO so that your treatment will work best for you.
Who should not use ALTUVIIIO?
You should not use ALTUVIIIO if you have had an allergic reaction to it in the past.
What should I tell my healthcare provider before using ALTUVIIIO?
Tell your healthcare provider if you have had any medical problems, take any medications, including prescription and non-prescription medicines, supplements, or herbal medicines, are breastfeeding, or are pregnant or planning to become pregnant.
What are the possible side effects of ALTUVIIIO?
You can have an allergic reaction to ALTUVIIIO. Call your healthcare provider or emergency department right away if you have any of the following symptoms: difficulty breathing, chest tightness, swelling of the face, rash, or hives.
Your body can also make antibodies called “inhibitors” against ALTUVIIIO. This can stop ALTUVIIIO from working properly. Your healthcare provider may give you blood tests to check for inhibitors.
The common side effects of ALTUVIIIO are headache, joint pain, and back pain.
These are not the only possible side effects of ALTUVIIIO. Tell your healthcare provider about any side effect that bothers you or does not go away.
Please see full Prescribing Information.
About the Sanofi and Sobi collaboration
Sobi and Sanofi collaborate on the development and commercialization of Alprolix® and Elocta®/Eloctate®. The companies also collaborate on the development and commercialization of efanesoctocog alfa, or ALTUVIIIO in the US. Sobi has final development and commercialization rights in the Sobi territory (essentially Europe, North Africa, Russia and most Middle Eastern markets). Sanofi has final development and commercialization rights in North America and all other regions in the world excluding the Sobi territory.
About Sobi®
Sobi is a specialised international biopharmaceutical company transforming the lives of people with rare and debilitating diseases. Providing reliable access to innovative medicines in the areas of haematology, immunology and specialty care, Sobi has approximately 1,600 employees across Europe, North America, the Middle East, Asia and Australia. In 2022, revenue amounted to SEK 18.8 billion. Sobi’s share (STO:SOBI) is listed on Nasdaq Stockholm. More about Sobi at sobi.com, LinkedIn and YouTube.
About Sanofi
We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across some 100 countries, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions. Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY
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