Afstyla for Hemophilia

Last updated Sept. 15, 2022 by Teresa Carvalho, MS

Fact-checked by Joana Carvalho, PhD


What is Afstyla for Hemophilia?

Afstyla (lonoctocog alfa) is an injectable factor replacement therapy used for the treatment and prevention of bleeding episodes in people with hemophilia A.

The therapy is marketed by CSL Behring.

How does Afstyla work?

Hemophilia A is an inherited bleeding disorder that prevents blood from clotting normally due to the lack of a protein called factor VIII (FVIII).

Afstyla is produced in Chinese hamster ovary cells as a single-chain polypeptide — a molecule made up of a string of amino acids, which are the basic units of proteins. Its active substance, lonoctocog alfa, is a single-chain recombinant, or man-made version of FVIII that, once activated, works in the same way as natural FVIII, providing long-lasting bleed protection.

Who can take Afstyla?

Afstyla was approved by both the U.S. Food and Drug Administration (FDA) and Health Canada in 2016 as a treatment for adults and children with hemophilia A. The following year, it was approved for the same indication in Europe.

The therapy is indicated for routine prophylaxis to prevent or reduce bleeding frequency, and also can be used as an on-demand treatment to control bleeds. It also is indicated for bleed management during surgery.

Who should not take Afstyla?

Afstyla should not be used by patients who have had previous severe and potentially life-threatening allergic reactions to the treatment or any of its components, as well as to hamster proteins.

How is Afstyla administered?

Afstyla is available as a white or slightly yellow dried powder supplied in single-use bottles containing 250, 500, 1,000, 1,500, 2,000, 2,500, and 3,000 international units (IU).

Given via an injection directly into a vein, it can be self-administered or administered by a caregiver. Anyone administering the therapy must first receive proper training from an experienced healthcare provider to ensure the medication is given correctly. The dosage may be adjusted based on a patient’s response.

For prophylactic or preventive treatment, the medication should be given at the following doses:

  • 20 to 50 IU per kilogram of body weight (IU/kg), given two to three times weekly, in the case of adults and adolescents ages 12 and older.
  • 30 to 50 IU/kg, two to three times weekly, in the case of children under age 12.

For on-demand treatment, Afstyla should be given to maintain FVIII activity levels at:

  • 20 to 40 IU/dL, with dosing every 12–24 hours until the bleed is resolved, in the case of minor bleeds.
  • 30 to 60 IU/dL, with dosing every 12–24 hours until the bleed is resolved, in the case of moderate bleeds.
  • 60 to 100 IU/dL, with dosing every 8–24 hours until the bleed is resolved, in the case of major or life-threatening bleeds.

For minor surgical procedures, Afstyla should be given every 24 hours for at least one day and until healing is achieved, to maintain FVIII activity levels at 30 to 60 IU/dL.

For major surgical procedures, patients should get Afstyla doses every 8–24 hours until healing is achieved to maintain FVIII activity levels at 80 to 100 IU/dL. The therapy should then be given for an additional period of at least seven days to maintain FVIII activity levels at 30 to 60 IU/dL.

The medication should be reconstituted, or diluted, before injection, using the Mix2Vial needle-free reconstitution and transfer system. The rate of administration should be adjusted according to the patient’s comfort level, and should not exceed 10 mL per minute.

Afstyla can be stored at room temperature or in the refrigerator, for up to three months. If stored at room temperature, the medication should not be returned to the fridge. After reconstitution, Afstyla should be administered right away or within four hours.

Afstyla in clinical trials

Phase 2/3 and Phase 3 trials

Afstyla’s approvals were supported by data from two pivotal trials — a Phase 2/3 study (NCT01486927), enrolling adolescents and adults ages 12–65, and a Phase 3 study (NCT02093897) that involved children under 12. Findings from an open-label extension study (NCT02172950) also were used to support the therapy’s approval.

All were part of the the AFFINITY clinical development program.

Data showed the median annualized spontaneous bleeding rate was zero in all studies. For patients undergoing prophylaxis with Afstyla, the median annualized bleeding rate was 1.14 in adults and adolescents, and 3.69 in children younger than 12.

Of the 1,195 bleeds treated in the pivotal studies (848 in adults and adolescents; 347 in children), about 94% of those in adults and adolescents and 96% of them in children were effectively controlled with no more than two infusions of Afstyla weekly. Also, about 81% of bleeds in adults and adolescents, and 86% in pediatric patients were effectively controlled by only one infusion.

Among the 13 adolescents and adults who underwent surgical procedures, Afstyla’s ability to stop bleeds was rated as excellent in 15 surgeries and as good in one procedure.

Ongoing trials

OPERA

CSL Behring is sponsoring a non-interventional, prospective study, called OPERA (NCT04675541), that is underway in several sites in France. The study aims to record real-life data in hemophilia A patients treated with Afstyla. The goal is to confirm the treatment’s efficacy and safety over a period of three years. The study is expected to be completed in December 2024.

Common side effects of Afstyla

The most common side effects associated with Afstyla include:

  • dizziness
  • hypersensitivity (allergic reactions)

Allergic reactions

Patients may develop a severe allergic reaction to Afstyla. The treatment is contraindicated, or not recommended, for people with known severe allergies to hamster proteins or to other therapy components. If symptoms occur, Afstyla should be stopped and patients should immediately seek emergency treatment.

Development of inhibitors

Neutralizing antibodies against FVIII, also known as inhibitors, may develop during treatment with Afstyla. Patients should be closely monitored for the development of such inhibitors. In cases where FVIII activity levels are not attained, or bleeds fail to be kept under control following treatment with Afstyla, the presence of inhibitors should be suspected.

Use in pregnancy and breastfeeding

It is still unknown if Afstyla can affect a developing fetus or pass to breast milk. Pregnant or breastfeeding women should seek medical advice before starting treatment.

 


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