Afstyla

Afstyla (lonoctocog alfa) is a single-chain recombinant, or man-made, version of factor VIII (FVIII) — the clotting protein missing or defective in people with hemophilia A — marketed by CSL Behring.

It was approved by the U.S. Food and Drug Administration (FDA) in 2016 to treat adults and children with hemophilia A. The following year, it was approved for the same indication in Europe.

The therapy is indicated for on-demand treatment to control bleeds, as a routine prophylaxis or preventive treatment to reduce bleeding frequency, and to manage bleeds during surgery.

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 FVIII.

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

Afstyla in clinical trials

Afstyla’s approval was based on results from two pivotal trials (NCT01486927NCT02093897) and one open-label extension study (NCT02172950) that evaluated the safety and efficacy of Afstyla in children, adolescents, and adults with hemophilia A.

Data showed the median annualized spontaneous bleeding rate — the number of bleeds that occur over a year without an obvious cause — 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 bleeds in adults and adolescents and 96% 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.

Other details

Afstyla is injected directly into the bloodstream. The therapy 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, or 3,000 international units (IU).

As a routine prophylaxis in adults and adolescents, ages 12 or older, the recommended starting regimen is 20 to 50 IU per kg of Afstyla given two to three times weekly. In children younger than 12, the recommended starting dose is 30 to 50 IU per kg of Afstyla two to three times weekly. Dosage may be adjusted based on a patient’s response.

The most common side effects associated with Afstyla include dizziness and allergic reactions such as rash or hives, itching, tightness in the chest or throat, difficulty breathing, lightheadedness, nausea, or a decrease in blood pressure.

In some cases, neutralizing antibodies against FVIII, also known as inhibitors, may develop. Afstyla should be used with caution if a patient is taking other medications, supplements, or herbal remedies. Pregnant or breastfeeding women should seek medical advice before starting treatment.

Afstyla should not be used if a patient experienced a life-threatening allergic reaction (anaphylaxis) to it in the past, or is allergic to its ingredients or to hamster proteins.

 

Last updated: Feb. 1, 2022, by Teresa Carvalho MS

 


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