Esperoct® [antihemophilic factor (recombinant), glycopegylated-exei] is a coagulation factor VIII (FVIII) concentrate indicated for the on-demand treatment and control of episodes of bleeding, the management of perioperative bleeding, and routine prophylaxis to decrease the incidence of episodes of bleeding in adults and children with hemophilia A.1 Esperoct is  a sterile, preservative-free, and non-pyrogenic lyophilized powder that is injected intravenously following reconstitution with the supplied saline diluent. Esperoct contains an active ingredient, a recombinant analogue of human FVIII, that is conjugated to a 40-kDa polyethylene glycol (PEG) molecule. Sodium chloride, sucrose, polysorbate 80, L-methionine, L-histidine, and calcium chloride are among the excipients in the Esperoct formulation.2 Manufactured by Novo Nordisk, Esperoct has been approved by the US Food and Drug Administration (FDA) since 2019 for on-demand treatment, perioperative management, and routine prophylaxis in children and adults with hemophilia A.2 The use of Esperoct to treat von Willebrand disease is not recommended.1 

Mechanism of Action

In patients with congenital hemophilia, Esperoct, a glycopegylated version of recombinant antihemophilic factor, provides a temporary source of coagulation FVIII, which is required for effective hemostasis and is absent in patients with hemophilia A. The FVIII in Esperoct is conjugated to a 40-kDa polyethylene glycol molecule, which increases its half-life by slowing clearance from the blood.3 The administration of ESPEROCT temporarily raises plasma levels of FVIII and corrects the abnormal coagulation, evidenced by a reduction in the activated partial thromboplastin time (aPTT).3 

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Efficacy in Trials and Trial Results

Safety and Efficacy 

Esperoct was approved by the FDA on the basis of the pathfinder program, which included 5 prospective, multicenter clinical trials enrolling 270 previously treated patients with severe hemophilia A (endogenous FVIII activity <1% of normal) and no history of inhibitor development. Patients were exposed to Esperoct for a total of 80,425 days, the equivalent of 889 patient-years of treatment. Esperoct delivered effective prophylaxis in persons with severe hemophilia A at a set dose of 1 injection every 4 days in adults and adolescents, and twice weekly in children. At a dose of 50 IU/kg every 4 days, Esperoct achieved excellent prophylaxis, with a low median annualized bleeding rate (ABR) of 1.18 in adults and adolescents. It also proved to be effective in the treatment and control of episodes of bleeding, as well as in perioperative care.4

The incidence of adverse effects was 0.10 per patient-year of exposure during clinical trials in previously treated patients. Rashes (5.2%), injection site reactions (2.6%), redness (1.9%), and pruritus (1.5%) were the most commonly reported side effects.5 

Routine Prophylaxis in Adolescents/Adults  

Routine prophylaxis with dosing every 4 days was established in adults and adolescents. A total of 186 patients had 159 exposure years during the Main Phase of the adolescent/adult study. The median ABR for treated bleeds in adults and adolescents treated every 4 days was 1.2, and the mean ABR was 3.0. When all bleeds (treated and untreated) were considered, the median ABR was 1.2, and the mean ABR was 3.3.

Routine Prophylaxis in Children Younger Than 12 Years Old  

A total of 68 children received prophylactic therapy twice a week at an average dose of 65 IU/kg. The prophylactic benefit was proven by a median ABR of 2.0 for treated bleeds and of 2.0 for all bleeds. The mean ABRs (SD) for treated bleeds and all bleeds, respectively, were 3.1 (7.1) and 4.4 (8.7). During the Main Phase of the trial, 32% of the 68 children did not have any episodes of bleeding, and 43% did not have any bleeding events that required treatment.6 

Warnings, Precautions, and Adverse Reactions

Patients with documented hypersensitivity to Esperoct or any of its components, such as hamster proteins, should not use it. If a hypersensitivity reaction to Esperoct develops, the drug should be stopped immediately, and medical attention is advised. The formation of  neutralizing antibodies (inhibitors) has also been noted. An assay measuring the FVIII inhibitor concentration should be performed if uncontrollable bleeding occurs with the Esperoct standard dose or if the expected plasma FVIII activity levels are not achieved.7 Rashes, redness, pruritus, and injection site reactions were the most commonly reported adverse effects, with an incidence of more than 1% in clinical trials.2 

References

  1. ESPEROCT (fda.gov). Package insert.  Novo Nordisk; 2019. Accessed December 19, 2021.
  2. Esperoct PI (novo-pi.com). Prescribing information. Revised October 2019. Accessed December 19, 2021.
  3. Clinical review, February 13, 2019 – ESPEROCT. Updated July 7, 2019, Accessed December 19, 2021.
  4. Esperoct [antihemophilic factor (recombinant), glycopegylated-exei]. Wcg CenterWatch. Accessed December 19, 2021.
  5. Esperoct ([antihemophilic factor (recombinant), glycopegylated-exei] injection). RxList. Updated March 7, 2019. Accessed December 19, 2021.
  6. Esperoct ([antihemophilic factor (recombinant), glycopegylated-exei] injection]). empr.com. Accessed December 19, 2021.
  7. DailyMedESPEROCT (antihemophilic factor- recombinant, glycopegylated-exei kit. Updated October 30, 2019, Accessed December 19, 2021.

Reviewed by Hasan Avcu, MD, on 12/26/2021.