Challenges persist in managing hemophilia with inhibitors

Hemophilia A with Inhibitors

Patients with HBwI are clinically underserved with a dire need for additional prophylaxis treatments^1,2

High rate of bleeds occurred with current treatment options³

High rate of bleeds occurred with current treatment options^2,3

Median ABR of

Patients using
on-demand BPAs
(n=16)

Median ABR of

Patients using
BPAs as prophylaxis
(n=15)

A descriptive, cross-sectional analysis was conducted using baseline characteristics and historical data including ABRs and treatment duration to describe real-world unmet needs in males aged ≥12 years with severe HA, moderate/severe HB, or HAwI/HBwI of any severity (N=31 patients with HBwI). BPAs were used on demand (n=16) for 111 months (mean) and as prophylaxis (n=15) for 85 months (mean). Due to the non-interventional design, study was subject to selection bias.³

Until now, the standard of care option for bleed prevention left HBwI patients vulnerable to^4,5:

Severe allergic reactions (anaphylaxis)^2,4

Numerous IV infusion steps involving reconstitution⁴

Multiple infusions per week for prophylaxis⁴

How do your patients’ bleeds affect outcomes such as hospitalizations, absenteeism, or mobility challenges?

ABR=annualized bleeding rate; BPA=bypassing agent; HA=hemophilia A; HAwI=hemophilia A with inhibitors; HB=hemophilia B; HBwI=hemophilia B with inhibitors; IV=intravenous.

Hemophilia B with Inhibitors

Significant treatment burden remains for patients managing HAwI^2,6-10

Bleeds still occur
despite standard of care^2,11

~50^%

n=70

of patients on FVIII mimetic experienced at least 1 spontaneous bleed^8,a

^aIn a real-world observational study at the Israeli National Hemophilia Center, breakthrough bleeding patterns were analyzed in patients with severe HA or HAwI receiving FVIII mimetic therapy prophylactically and completing 18 months of follow-up (n=28 patients with HAwI and 42 with HA without inhibitors). Results include patients with HA with and without inhibitors. Findings have not been confirmed by a clinical or randomized-controlled trial.⁸

Time-consuming administration⁷
Up to 15 minutes or more to prepare and inject FVIII mimetic

Pain and discomfort^7,9-10
Large volume and large needles (up to 25G) in subcutaneous administration

Multiple steps and supplies⁷
Prepare and administer treatment with vials and syringes

There can be uncertainty surrounding individual response to treatment and limited ability to measure⁶

FVIII=Factor VIII; HA=hemophilia A; HA=hemophilia A; HAwI=hemophilia A with inhibitors.

Important Safety Information for Alhemo^®

Contraindications

Alhemo^® is contraindicated in patients with a history of known serious hypersensitivity to Alhemo^® or its ingredients

Warnings and Precautions

Thromboembolic Events (TEs): Venous and arterial TEs were reported in 1.3% of patients (4/320) who also had multiple risk factors, including the use of high doses or prolonged treatment with factor products or bypassing agents (2 of 4 events). Risk factors for TEs may also include conditions in which tissue factor is overexpressed (eg, atherosclerotic disease, crush injury, cancer, disseminated intravascular coagulation, thrombotic microangiopathy, or septicemia).
Inform patients about and monitor them for signs and symptoms of TEs. In case of suspicion of TEs, discontinue Alhemo^® and initiate further investigations and management strategies

Indications and Usage

Alhemo^® (concizumab-mtci) injection 60 mg, 150 mg, or 300 mg is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years of age and older with hemophilia A with FVIII inhibitors and hemophilia B with FIX inhibitors.

Important Safety Information cont'd

Warnings and Precautions cont'd

Hypersensitivity Reactions: Alhemo^® is contraindicated in patients with a history of known serious hypersensitivity to Alhemo^® or its ingredients. Hypersensitivity reactions, including erythema, rash, pruritus, and abdominal pain, have occurred in patients treated with Alhemo^®. One patient (<1%) experienced anaphylaxis, which resolved after treatment with antihistamines and corticosteroids. Instruct patients of the signs of acute hypersensitivity reactions and to contact their healthcare provider for mild reactions and to seek urgent medical attention for moderate to severe reactions. Discontinue Alhemo^® if severe hypersensitivity symptoms occur, and initiate medical management
Increased Laboratory Values of Fibrin D-dimer and Prothrombin Fragment 1.2: Increased levels of fibrin D-dimer and prothrombin fragment 1.2 were seen in 29 (9.1%) and 18 (5.6%) patients, respectively, which is positively correlated with the plasma concentration of concizumab-mtci, indicating a hemostatic effect. For patients taking Alhemo^®, these coagulation biomarkers may not be reliable predictive markers for clinical decision-making with suspicion of thrombosis, such as deep vein thrombosis and pulmonary embolism

Adverse Reactions

The most frequently reported adverse reactions (≥5%) were injection site reactions and urticaria
Serious adverse reactions were reported in 6.1% of patients who received Alhemo^®. Permanent discontinuation of Alhemo^® occurred in 1 patient due to a renal infarct and dosage interruptions of Alhemo^® occurred in 1 patient (3%) and was a hypersensitivity reaction

Drug Interactions

Bypassing Agents (BPAs): Take appropriate precautions when treating breakthrough bleeding events in hemophilia patients receiving Alhemo^® prophylaxis and a BPA (eg, rFVIIa or aPCC). For mild and moderate bleeds, the lowest approved dose in the approved BPA product labeling is recommended. For aPCC, a maximum dose of 100 units/kg within 24 hours is recommended. For severe bleeds, follow the dosing instructions in the approved labeling based on clinical judgment

Please click here for Alhemo^® Prescribing Information.

References:

Lewandowska M, Nasr S, Shapiro AD. Emerging therapies in hemophilia: improving equitable access to care. J Blood Med. 2025;16:95-115.
Srivastava A, Santagostino E, Dougall A, et al. WFH guidelines for the management of hemophilia. Haemophilia. 2020;26(suppl 6):1-158.
Windyga J, Apte S, Frei-Jones M, et al. Disease and treatment burden of patients with haemophilia entering the explorer6 non-interventional study. J Haematol. 2024;113(5):631-640.
FEIBA^® [package insert]. Takeda Pharmaceuticals USA, Inc; 2024.
Shapiro AD, Mitchell IS, Nasr S. The future of bypassing agents for hemophilia with inhibitors in the era of novel agents. J Thromb Haemost. 2018;16(12):2362-2374. doi:10.1111/jth.14296
Nardi MA. Hemophilia A: emicizumab monitoring and impact on coagulation testing. Adv Clin Chem. 2023;113:273-315.
HEMLIBRA^® [package insert]. Genentech, Inc; 2024.
Levy-Mendelovich S, Brutman-Barazani T, Budnik I, et al. Real-world data on bleeding patterns of hemophilia A patients treated with emicizumab. J Clin Med. 2021;10(19):4303.
Arendt-Nielsen L, Egekvist H, Bjerring P. Pain following controlled cutaneous insertion of needles with different diameters. Somatosens Mot Res. 2006;23(1-2):37-43.
Usach I, Martinez R, Festini T, Peris JE. Subcutaneous injection of drugs: literature review of factors influencing pain sensation at the injection site. Adv Ther. 2019;36:2986-2996.
National Bleeding Disorders Foundation. MASAC Document #268. MASAC Recommendations on the use and management of emicizumab-kxwh (Hemlibra^®) for hemophilia A with and without inhibitors. National Bleeding Disorders Foundation. Adopted April 27, 2022. Accessed May 16, 2025. https://www.bleeding.org/sites/default/files/document/files/268_Emicizumab.pdf