Hemophilia

Eloctate^® (Antihemophilic Factor [Recombinant], Fc Fusion Protein) is an antihemophilic factor indicated for the on-demand treatment and control of episodes of bleeding, the perioperative management of bleeding, and routine prophylaxis to reduce the frequency of episodes of bleeding in adults and children with hemophilia A.¹ Hemophilia A is caused by a congenital deficiency of clotting factor VIII (FVIII). Patients with hemophilia A bleed longer than other people. Bleeding into the joints and muscles may occur, and in the severe form of the disease, episodes of bleeding may be spontaneous.²

Eloctate is a sterile lyophilized powder to be administered intravenously after reconstitution. Eloctate was first approved by the US Food and Drug Administration (FDA) in 2014 and is marketed by Sanofi.¹ 

Mechanism of Action

The treatment of hemophilia A relies on the replacement of FVIII, so that clots can form properly and bleeding be prevented. Patients receive a concentrated FVIII product, which can be either plasma-derived or recombinant. Recombinant factor products such as Eloctate are developed with DNA technology.² The active ingredient in Eloctate is B-domain deleted recombinant FVIII, FC fusion protein (BDD-rFVIIIFc), which is a recombinant protein in which the B-domain deleted analogue of human FVIII is covalently linked to the Fc domain sequence of human immunoglobulin G₁.¹ No animal- or human-derived proteins are used in the formulation process, and the production process includes 2 steps for viral clearance.¹

Eloctate replaces FVIII, but only temporarily. Because Fc fusion technology is used to produce Eloctate, the protein can bind to the neonatal Fc receptor (FcRn). Immunoglobulin degradation is therefore delayed, and the plasma half-life of the drug is increased.¹ 

Get full prescribing information on Eloctate at MPR

Eloctate in Clinical Trials

The safety and pharmacokinetics of a single dose of rFVIIIFc was initially evaluated in a phase I trial (NCT01027377),³ which was followed by 2 phase III trials in adults and children: A-LONG (NCT01181128) and Kids A-LONG (NCT01458106).^4-6 The results of these trials supported the use of rFVIIIFc as an extended half-life treatment for patients with hemophilia A.

A-LONG was a multicenter open-label study involving 165 previously treated patients with hemophilia A who were at least 12 years old.⁴ Patients were randomized to receive individualized prophylaxis with drug administration every 3 to 5 days, weekly prophylaxis, or on-demand treatment during episodes of bleeding.⁴ In 98.8% of the patients who received prophylactic treatment, infusion frequency was decreased and the annualized bleeding rates were low.⁵ Episodes of bleeding resolved after a single injection of Eloctate in 87.3% of the patients.⁴

In the open-label Kids A-LONG trial, the safety, efficacy, and pharmacokinetics of rFVIIIFc were evaluated. A total of 71 participants were enrolled in the study.⁶ Patients received infusions twice a week. Results of the trial revealed that 93% of the episodes of bleeding were managed with 1 or 2 infusions.⁶

An extension study, ASPIRE (NCT01454739), included 179 adults and adolescents at least 12 years old and 61 patients younger than 12 years old.^7,8 Participants in this study had previously participated in A-LONG or Kids A-LONG. The ASPIRE trial confirmed the safety profile and efficacy of Eloctate, showing that the annualized bleeding rate remained low in the participants treated with a prophylaxis regimen.^7,8

Uses, Warnings, and Adverse Reactions

The appropriate dose of Eloctate depends on the severity of disease, the location and severity of bleeding, and the patient’s profile. The recommended dose (50 IU/kg twice weekly) may require adjustment for patients younger than 6 years old.¹

Eloctate may induce hypersensitivity reactions and the formation of neutralizing antibodies (inhibitors). It is contraindicated in patients who have experienced life-threatening reactions to any component of Eloctate.¹ The most common adverse reactions observed in the clinical trials included myalgia, malaise, headache, arthralgia, and rash.¹

References

1. ELOCTATE^® (Antihemophilic factor [recombinant], Fc Fusion protein). Package insert. Sanofi; revised 12/2020. Accessed December 17, 2021. 

2. Hemophilia A. National Hemophilia Foundation. Accessed December 17, 2021.

3. Powell JS, Josephson NC, Quon D, et al. Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia A patients. Blood. 2012;119(13):3031-7. doi:10.1182/blood-2011-09-382846

4. Mahlangu J, Powell JS, Ragni MV, et al. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood. 2014;123(3):317-25. doi:10.1182/blood-2013-10-529974

5. Shapiro AD, Ragni MV, Kulkarni R, et al. Recombinant factor VIII Fc fusion protein: extended-interval dosing maintains low bleeding rates and correlates with von Willebrand factor levels. J Thromb Haemost. 2014;12(11):1788-800. doi:10.1111/jth.12723

6. Young G, Mahlangu J, Kulkarni R, et al. Recombinant factor VIII Fc fusion protein for the prevention and treatment of bleeding in children with severe hemophilia A. J Thromb Haemost. 2015;13(6):967-77. doi:10.1111/jth.12911

7. Nolan B, Mahlangu J, Pabinger I, et al. Recombinant factor VIII Fc fusion protein for the treatment of severe haemophilia A: final results from the ASPIRE extension study. Haemophilia. 2020;26(3):494-502. doi:10.1111/hae.13953

8. Nolan B, Mahlangu J, Perry D, et al. Long-term safety and efficacy of recombinant factor VIII Fc fusion protein (rFVIIIFc) in subjects with haemophilia A. Haemophilia. 2016;22(1):72-80. doi:10.1111/hae.12766

Reviewed by Debjyoti Talukdar, MD, on 12/18/2021.

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Diana Diez Gaspar, PharmD, PhD

Diana earned her PhD and PharmD with distinction in the field of Medicinal and Pharmaceutical Chemistry at the Universidade do Porto. She is an accomplished oncology scientist with 10+ years of experience in developing and managing R&D projects and research staff directed to the development of small proteins fit for medical use.