Hemophilia

Afstyla^® is a novel, single-chain recombinant form of antihemophilic factor (factor VIII) that is used to treat adults and children with hemophilia A. Indications include the management of episodes of bleeding, routine prophylaxis to decrease the frequency of bleeding, and the management of perioperative bleeding.¹ Afstyla is the first and only single-chain product for use in patients with hemophilia A. Dosed 2 to 3 times weekly, this product was specifically developed to provide long-term protection against episodes of bleeding.² It is injected intravenously and can be self-administered by the patient or administered by a caregiver. The infusion technique is taught to the patient by a healthcare professional or at a hemophilia treatment center. If the patient is found to be allergic to any of the components of Afstyla, or to hamster proteins, the drug should be avoided.³ 

Afstyla is a brand name. The generic name of the drug is antihemophilic factor (recombinant), single chain. Afstyla was approved by the US Food and Drug Administration on May 25, 2016, under the company name CSL Behring for the treatment of hemophilia A.⁴ 

Mechanism of Action

Hemophilia A is an X-linked hereditary disorder of blood coagulation in which blood levels of factor VIII are below normal. The deficiency leads to bleeding into muscles, joints, and internal organs, which is either spontaneous or due to trauma (accidental or surgical).¹ 

Afstyla is a recombinant protein that acts as a replacement for coagulation factor VIII, which is required for proper hemostasis. It consists of a single polypeptide chain with a shortened B-domain that allows the factor VIII heavy and light chains to be linked via a covalent bridge. In comparison with full-length recombinant factor VIII, Afstyla has a stronger affinity for von Willebrand factor (VWF). VWF stabilizes and thus prevents the degradation of factor VIII. The amino acid sequence of activated Afstyla is similar to that of endogenous activated factor VIII (FVIIIa).⁵ 

Get full prescribing information for Afstyla at MPR

Efficacy in Trials and Trial Results

The efficacy and safety of Afstyla have been demonstrated in 2 studies. One is an open-label, multicenter, crossover trial of the safety, efficacy, and pharmacokinetics of Afstyla in adults and adolescents. The other is an open-label study of the pharmacokinetics, efficacy, and safety of Afstyla in children.¹ 

On-Demand Treatment and Control of Episodes of Bleeding 

Afstyla was used to treat a total of 848 episodes of bleeding in the adult/adolescent study, The investigator conducted an efficacy assessment for Afstyla in 835 of these episodes. A single injection of Afstyla was sufficient to manage 686 of the 848 bleeding events (81%), 2 injections were required in 107 cases (13%), and 3 or more injections were required in 55 cases (6%). The investigator rated the hemostatic efficacy of Afstyla as excellent or good in 94% of the bleeding events.¹ In the pediatric trial, Afstyla was used to treat 347 episodes of bleeding, and the investigator evaluated the efficacy of Afstyla in all of these. Of the 347 episodes, 298 (86%) could be managed with a single injection of Afstyla, 34 (10%) required 2 injections, and 15 (4%) required 3 or more injections. The investigator rated the hemostatic efficacy of Afstyla as excellent or good in 96% of the bleeding events.¹ 

Routine Prophylaxis to Decrease the Frequency of Episodes of Bleeding

The annualized bleeding rate (ABR) in adults and adolescents receiving prophylaxis (median, 1.14) was considerably lower (P =.0001) than the ABR in patients treated on demand (median, 19.64). While on prophylaxis, 63 of 146 patients (43%) had no episodes of bleeding. No serious or life-threatening bleeds occurred in the participants who received prophylaxis​​.⁵ 

Perioperative Management of Bleeding

In the adult/adolescent trial, 13 individuals underwent 16 surgical procedures. In general, investigators rated the hemostatic performance of Afstyla in the management of perioperative bleeding as outstanding in 15 of 16 procedures and good in 1 procedure.⁵

Warnings, Precautions and Adverse Reactions

Before treatment is started, the presence of factor VIII deficiency should be confirmed. Adverse effects include dizziness and hypersensitivity reactions. Patients should be made aware of the early signs of hypersensitivity reactions, which can lead to anaphylaxis. If a hypersensitivity reaction takes place, Afstyla should be discontinued and proper treatment started. The patient can also be premedicated with an antihistamine in such cases.^1,6,7 

Neutralizing antibodies (inhibitors) to factor VIII have been identified after treatment with Afstyla. Previously untreated patients are at higher risk. A Bethesda inhibitor assay should be done to evaluate the factor VIII inhibitor concentration if the anticipated plasma activity levels are not achieved, or if bleeding is not controlled with the recommended dose. Bethesda units (BU) are used to report inhibitor levels.^1,5 Plasma factor VIII activity is monitored with the chromogenic assay or the 1-stage clotting assay.⁵ Other side effects of Afstyla include rash, paresthesia, erythema, dizziness, pyrexia, itching, chills, feeling hot, fever, and pain at the injection site.⁶ 

References

1. AFSTYLA^®, antihemophilic factor (recombinant), single chain. Package insert. CSL Behring; 2020. Accessed December 8, 2021.
2. McKee S. FDA nod for CSL’s long-acting hemophilia drug. News release. PharmaTimes online; May 27, 2016, Accessed December 7, 2021. 
3. AFSTYLA^®, antihemophilic factor (recombinant), single chain. CSL Behring. Accessed December 8, 2021. 
4. Afstyla FDA approval history. Drugs.com. Accessed December 8, 2021.
5. AFSTYLA^®, antihemophilic factor (recombinant), single chain. antihemophilic factor, human recombinant kit. DAILYMED, US National Library Of Medicine. Updated June 21, 2021. Accessed December 8, 2021.
6. AFSTYLA Rx. MPR.  Accessed December 8, 2021.
7. AFSTYLA®, antihemophilic factor (recombinant), single chain. wcg CenterWatch. Accessed December 8, 2021. 

Reviewed by Debjyoti Talukdar, MD, on 12/7/2021.

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Harshi Dhingra, MD

Harshi Dhingra is a licensed medical doctor with specialization in Pathology. She is currently employed as faculty in a medical school with a tertiary care hospital and research center in India. Dr. Dhingra has over a decade of experience in diagnostic, clinical, research, and teaching work, and has written several publications and citations in indexed peer reviewed journals. She holds medical degrees for MBBS and an MD in Pathology.