ALTUVIIIO: CLINICAL EVIDENCE
Knowledge of how a treatment impacts the underlying condition is important when evaluating the clinical value that it brings
ALTUVIIIO IS THE FIRST FVIII REPLACEMENT THERAPY TO OVERCOME THE HALF-LIFE LIMITATIONS IMPOSED BY VWF1-3
MECHANISM OF EXTENSION
Structure of ALTUVIIIO3
From Konkle BA, et al. N Engl J Med. 2020;383:1018-1027. © 2022 Massachusetts
Medical Society. Reused with permission from Massachusetts Medical Society.
THE SLOPE MAKES A DIFFERENCE
FVIII activity levels with ALTUVIIIO remained higher for a longer duration compared with other FVIII products1*
*Data from a Phase 1 trial in 13 previously treated adults with severe hemophilia A. PK profiles of ALTUVIIIO, Advate, and Adynovate were evaluated after sequential IV infusions.1
Advate and Adynovate are registered trademarks of Baxalta Incorporated, a Takeda company.
ALTUVIIIO CLINICAL TRIALS
ALTUVIIIO was studied in a robust clinical program4,5
XTEND-1 trial
Open-label, multicenter, Phase 3 study of ALTUVIIIO in previously treated patients5
Adults and adolescents (aged ≥12 years) with severe hemophilia A who had been previously treated with any recombinant and/or plasma-derived FVIII cryoprecipitate for ≥150 exposure days were eligible to participate in the study.
A subset enrolled in a 12-month observational prestudy
A total of 92 patients rolled over from the observational prestudy into XTEND-1, including 82 patients into the prior FVIII prophylaxis group (Arm A) and 10 into the prior FVIII on-demand group (Arm B)
Primary endpoint: Mean annualized bleeding rate (ABR) in the prophylaxis treatment arm (Arm A).5
Key secondary endpoint: Intrapatient ABR comparison.5*
Additional secondary endpoints: Joint health outcomes (HJHS, target joint, joint ultrasound imaging†), quality of life (PROs, physical activity tracking†), ALTUVIIIO consumption, treatment of bleeds, perioperative management, safety and tolerability, and PK.5,6
*ABR during the ALTUVIIIO weekly prophylaxis treatment period (Arm A) vs ABR during prestudy prophylaxis from the prior prospective observational study (Study 242HA201/OBS16221).5 †Exploratory endpoint. ClinicalTrials.gov, NCT04161495.6
XTEND-1 study results
ALTUVIIIO delivered clinically meaningful bleeding protection4,5
The primary endpoint, the mean ABR, was 0.7 (95% Cl, 0.5-1.0) in the prior FVIII prophylaxis group (Arm A) (n=128).4,5
*Data from prospective observational study.5 Based on the negative binomial model.4
Patients who switched to ALTUVIIIO prophylaxis experienced a significant reduction in ABRs
The mean number of bleeding episodes reported during the 12 months prior to the study was 35.7 (SD: 22.2) in the prior FVIII on-demand group.5
ALTUVIIIO prevented joint bleeds and substantially improved joint health5
Joint bleeds4
FVIII prophylaxis group (n=128): the median AjBR* was 0.0 (IQR, 0.0-1.0), and the mean AjBR† was 0.5 (95% CI, 0.4-0.7) at 52 weeks of prophylaxis.
FVIII on-demand group (n=26): the median AjBR* was 0.0 (IQR, 0.0-0.0), and the mean AjBR† was 0.6 (95% CI, 0.3-1.5) at 26 weeks of prophylaxis.
*Based on treated bleeds.4
†Based on the negative binomial model.4
Target joint resolution4*
All 45 target joints resolved (100%) among 45 patients who had target joints identified at baseline and at least 52 weeks of on-study prophylaxis.
*All patients with target joints (defined as ≥3 spontaneous bleeding episodes in a major joint that occurred in a consecutive 6-month period) at baseline achieved resolution (defined as ≤2 bleeding episodes in the target joint in 12 months) of all target joints (45/45, 100%) with 12 months of prophylaxis treatment with ALTUVIIIO.4
Joint health improvement5
The mean HJHS decreased from baseline to Week 52 (mean change, -1.5; 95% CI, -2.7 to -0.4).*
HJHS is a validated tool used to measure joint health. The open-label nature of the study may impact the interpretation of results.
*Mean change in total score from baseline to Week 52.5
XTEND-Kids
A 52-week, multinational, multicenter, single-arm, open-label, Phase 3 study of ALTUVIIIO4
Primary endpoint21: The occurrence of inhibitor development.
Secondary endpoint21: ABR for treated bleeds by type and location.
Additional secondary endpoints21
- Pharmacokinetics
- Safety and tolerability
- Perioperative management
- Treatment of bleeds
In children aged <12 years, ALTUVIIIO provided FVIII activity levels >40% for ~3 days, and an unprecedented overall mean steady-state trough of >10% at Day 7
ALTUVIIIO delivered effective bleed protection21
Most patients experienced zero bleeds when treated with ALTUVIIIO prophylaxis (N=72)21
Safety
ALTUVIIIO has an established safety profile21
No FVIII inhibitors were detected in Phase 3 clinical trials*
FVIII inhibitor formation is possible with ALTUVIIIO
All patients were monitored for FVIII inhibitors in the Phase 3 clinical programs
*Phase 3 clinical trials include XTEND-1 and XTEND-Kids.
Hypersensitivity reactions
ALTUVIIIO is contraindicated in patients who have had severe hypersensitivity reactions, including anaphylaxis, to the product or its excipients
No adverse allergic-type reactions, including anaphylaxis, were reported during Phase 3 studies
Allergic-type hypersensitivity reactions, including anaphylaxis, are possible with ALTUVIIIO
ADVERSE REACTIONS WITH FREQUENCY OF ≥3% REPORTED FOR ALTUVIIIO
| ADVERSE REACTIONS | Patients, n (%) (N=233*) |
| Headache | 35 (15) |
| Arthralgia | 31 (13) |
| Pain in extremity | 10 (4) |
| Back pain | 9 (4) |
| Pyrexia | 10 (4) |
| Vomiting | 7 (3) |
*233 subjects across the adult and adolescent and pediatric studies.
Please see the full Prescribing Information for complete details on dosing and administration.
The value of ALTUVIIIO
See how ALTUVIIIO’s simple, fixed-dosing regimen may help payers predict the impact to their budgets.22
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AjBR=annualized joint bleeding rate; Fc=fragment crystallizable; HJHS=Hemophilia Joint Health Score; IQR=interquartile range; IV=intravenous; PK=pharmacokinetic; PRO=patient-reported outcome; SD=standard deviation.
References: 1. Lissitchkov T, Willemze A, Jan C, Zilberstein M, Katragadda S. Pharmacokinetics of recombinant factor VIII in adults with severe hemophilia A: fixed-sequence single-dose study of octocog alfa, rurioctocog alfa pegol, and efanesoctocog alfa. Res Pract Thromb Haemost. 2023;7(4):100176. doi:10.1016/j.rpth.2023.100176 2. Chhabra ES, Liu T, Kulman J, et al. BIVV001, a new class of factor VIII replacement for hemophilia A that is independent of von Willebrand factor in primates and mice. Blood. 2020;135(17):1484-1496. doi:10.1182/blood.2019001292 3. Konkle BA, Shapiro AD, Quon DV, et al. BIVV001 fusion protein as factor VIII replacement therapy for hemophilia A. N Engl J Med. 2020;383(11):1018-1027. doi:10.1056/NEJMoa2002699 4. ALTUVIIIO. Prescribing information. Bioverativ Therapeutics Inc.; 2023. 5. von Drygalski A, Chowdary P, Kulkarni R, et al. Efanesoctocog alfa prophylaxis for patients with severe hemophilia A. N Engl J Med. 2023;388(4):310-318. doi:10.1056/NEJMoa2209226 6. Advate. Prescribing information. Takeda Pharmaceuticals U.S.A., Inc.; 2023. 7. Adynovate. Prescribing information. Takeda Pharmaceuticals U.S.A., Inc.; 2023. 8. Eloctate. Prescribing information. Bioverativ Therapeutics Inc.; 2023. 9. Afstyla. Prescribing information. CSL Behring GmbH; 2023. 10. Esperoct. Prescribing information. Novo Nordisk A/S; 2024. 11. Jivi. Prescribing information. Bayer HealthCare LLC; 2018. 12. Novoeight. Prescribing information. Novo Nordisk A/S; 2020. 13. Helixate. Prescribing information. Bayer HealthCare LLC; 2016. 14. Recombinate. Prescribing information. Takeda Pharmaceuticals U.S.A., Inc.; 2023. 15. Study to evaluate the safety, pharmacokinetics and efficacy of recombinant factor VIII Fc fusion protein (rFVIIIFc) in previously treated subjects with severe hemophilia A. NCT01181128. ClinicalTrials.gov. Updated January 8, 2021. Accessed November 11, 2023. https://clinicaltrials.gov/study/NCT01181128 16. Trial to evaluate the efficacy and safety of a new full length recombinant human FVIII for hemophilia A (Leopold I). NCT01029340. ClinicalTrials.gov. Updated November 28, 2016. Accessed November 11, 2023. https://clinicaltrials.gov/study/NCT01029340 17. Study evaluating “real world” treatment pattern in previously treated hemophilia A patients receiving KOVALTRY (octocog alfa) for routine prophylaxis (TAURUS). NCT02830477. ClinicalTrials.gov. Updated November 7, 2023. Accessed November 11, 2023. https://clinicaltrials.gov/study/NCT02830477 18. Non-interventional post-authorisation study to document the immunogenicity, safety, and efficacy of NUWIQ. NCT02962765. ClinicalTrials.gov. Updated October 21, 2021. Accessed November 11, 2023. https://clinicaltrials.gov/study/NCT02962765 19. Study evaluating prophylaxis treatment & characterizing efficacy, safety, & PK of B-domain deleted recombinant FVIII. NCT00543439. ClinicalTrials.gov. Updated January 11, 2019. Accessed November 11, 2023. https://clinicaltrials.gov/study/NCT00543439 20. Study to establish bioequivalence of ReFacto AF (BDDrFVIII) with Advate (FLrFVIII) in hemophilia A. NCT00141843. ClinicalTrials.gov. Updated April 22, 2008. Accessed November 11, 2023. https://clinicaltrials.gov/study/NCT00141843 21. Data on file. Bioverativ Therapeutics Inc. 22. Simpson ML, Desai V, Maro GS, Yan S. Comparing factor use and bleed rates in U.S. hemophilia A patients receiving prophylaxis with 3 different long-acting recombinant factor VIII products. J Manag Care Spec Pharm. 2020;26(4):504-512. doi:10.18553/jmcp.2020.19318
INDICATION
ALTUVIIIO® [antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl] is a von Willebrand Factor (VWF) independent recombinant DNA-derived, Factor VIII concentrate indicated for use in adults and children with hemophilia A (congenital factor VIII deficiency) for:
- Routine prophylaxis to reduce the frequency of bleeding episodes
- On-demand treatment & control of bleeding episodes
- Perioperative management of bleeding
Limitation of Use
ALTUVIIIO is not indicated for the treatment of von Willebrand disease.
CONTRAINDICATIONS
ALTUVIIIO is contraindicated in patients who have had severe hypersensitivity reactions, including anaphylaxis, to the product or its excipients.
WARNINGS AND PRECAUTIONS
- Allergic-type hypersensitivity reactions, including anaphylaxis, may occur with ALTUVIIIO. Allergic-type hypersensitivity reactions were not reported in the clinical trials. Advise patients to discontinue use of ALTUVIIIO if hypersensitivity symptoms occur and contact a physician and/or seek immediate emergency care.
- Formation of neutralizing antibodies (inhibitors) to Factor VIII is possible following administration of ALTUVIIIO. Neutralizing antibodies were not reported in the clinical trials. Monitor all patients for the development of Factor VIII inhibitors by appropriate clinical observations and laboratory tests.
- If assessment of plasma Factor VIII activity is needed, it is recommended to use a validated one-stage clotting assay. The ALTUVIIIO Factor VIII activity level is overestimated by the chromogenic assay and a specific ellagic acid-based aPTT reagent in one-stage clotting assay by approximately 2.5-fold. If these assays are used, divide the result by 2.5 to approximate the patient’s ALTUVIIIO Factor VIII activity level.
ADVERSE REACTIONS
The most common adverse reactions (>10% of subjects) reported in clinical trials were headache and arthralgia.
Please see full Prescribing Information.
Learn more about Sanofi’s commitment to fighting counterfeit drugs.
INDICATION
ALTUVIIIO® [antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl] is a von Willebrand Factor (VWF) independent recombinant DNA-derived, Factor VIII concentrate indicated for use in adults and children with hemophilia A (congenital factor VIII deficiency) for:
- Routine prophylaxis to reduce the frequency of bleeding episodes
- On-demand treatment & control of bleeding episodes
- Perioperative management of bleeding
Limitation of Use
ALTUVIIIO is not indicated for the treatment of von Willebrand disease.
CONTRAINDICATIONS
ALTUVIIIO is contraindicated in patients who have had severe hypersensitivity reactions, including anaphylaxis, to the product or its excipients.
WARNINGS AND PRECAUTIONS
- Allergic-type hypersensitivity reactions, including anaphylaxis, may occur with ALTUVIIIO. Allergic-type hypersensitivity reactions were not reported in the clinical trials. Advise patients to discontinue use of ALTUVIIIO if hypersensitivity symptoms occur and contact a physician and/or seek immediate emergency care.
- Formation of neutralizing antibodies (inhibitors) to Factor VIII is possible following administration of ALTUVIIIO. Neutralizing antibodies were not reported in the clinical trials. Monitor all patients for the development of Factor VIII inhibitors by appropriate clinical observations and laboratory tests.
- If assessment of plasma Factor VIII activity is needed, it is recommended to use a validated one-stage clotting assay. The ALTUVIIIO Factor VIII activity level is overestimated by the chromogenic assay and a specific ellagic acid-based aPTT reagent in one-stage clotting assay by approximately 2.5-fold. If these assays are used, divide the result by 2.5 to approximate the patient’s ALTUVIIIO Factor VIII activity level.
ADVERSE REACTIONS
The most common adverse reactions (>10% of subjects) reported in clinical trials were headache and arthralgia.
Please see full Prescribing Information.
Learn more about Sanofi’s commitment to fighting counterfeit drugs.
INDICATION
ALTUVIIIO® [antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl] is a von Willebrand Factor (VWF) independent recombinant DNA-derived, Factor VIII concentrate indicated for use in adults and children with hemophilia A (congenital factor VIII deficiency) for:
- Routine prophylaxis to reduce the frequency of bleeding episodes
- On-demand treatment & control of bleeding episodes
- Perioperative management of bleeding
Limitation of Use
ALTUVIIIO is not indicated for the treatment of von Willebrand disease.
CONTRAINDICATIONS
ALTUVIIIO is contraindicated in patients who have had severe hypersensitivity reactions, including anaphylaxis, to the product or its excipients.
WARNINGS AND PRECAUTIONS
- Allergic-type hypersensitivity reactions, including anaphylaxis, may occur with ALTUVIIIO. Allergic-type hypersensitivity reactions were not reported in the clinical trials. Advise patients to discontinue use of ALTUVIIIO if hypersensitivity symptoms occur and contact a physician and/or seek immediate emergency care.
- Formation of neutralizing antibodies (inhibitors) to Factor VIII is possible following administration of ALTUVIIIO. Neutralizing antibodies were not reported in the clinical trials. Monitor all patients for the development of Factor VIII inhibitors by appropriate clinical observations and laboratory tests.
- If assessment of plasma Factor VIII activity is needed, it is recommended to use a validated one-stage clotting assay. The ALTUVIIIO Factor VIII activity level is overestimated by the chromogenic assay and a specific ellagic acid-based aPTT reagent in one-stage clotting assay by approximately 2.5-fold. If these assays are used, divide the result by 2.5 to approximate the patient’s ALTUVIIIO Factor VIII activity level.
ADVERSE REACTIONS
The most common adverse reactions (>10% of subjects) reported in clinical trials were headache and arthralgia.
Please see full Prescribing Information.
Learn more about Sanofi’s commitment to fighting counterfeit drugs.
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ALTUVIIIO and Sanofi are registered trademarks of Sanofi or an affiliate.
