Alhemo: Uses, Dosage & Side Effects

What Is Alhemo and What Is It Used For?

Alhemo contains the active substance concizumab, which belongs to a class of medicines known as monoclonal antibodies. Monoclonal antibodies are laboratory-produced proteins designed to recognize and bind to a specific target in the body. In the case of concizumab, the target is tissue factor pathway inhibitor (TFPI), a naturally occurring protein that plays a critical role in regulating blood coagulation. By selectively binding to and blocking TFPI, concizumab removes a natural brake on the coagulation cascade, allowing blood to clot more efficiently in patients who have a deficiency in one of the essential clotting factors.

Hemophilia is an inherited bleeding disorder caused by a deficiency or absence of specific blood clotting proteins. Hemophilia A results from a deficiency of coagulation factor VIII, while hemophilia B is caused by a deficiency of factor IX. Both conditions lead to prolonged and sometimes spontaneous bleeding, particularly into joints (hemarthrosis), muscles, and other soft tissues. Without adequate treatment, recurrent joint bleeds can cause progressive joint damage (hemophilic arthropathy), chronic pain, and significant disability. Hemophilia affects approximately 1 in 5,000 male births for hemophilia A and 1 in 25,000 male births for hemophilia B worldwide.

A major challenge in hemophilia treatment is the development of inhibitors – antibodies produced by the patient’s immune system that neutralize the therapeutic clotting factor concentrates. Inhibitors render standard factor replacement therapy ineffective and represent one of the most serious complications in hemophilia care. Approximately 25–30% of patients with severe hemophilia A and 3–5% of patients with hemophilia B develop inhibitors at some point during their treatment. For these patients, bypassing agents such as activated prothrombin complex concentrate (aPCC) or recombinant activated factor VII (rFVIIa) have traditionally been used, but these treatments have variable efficacy and require frequent intravenous infusions.

Alhemo represents a fundamentally different approach to hemophilia prophylaxis. Rather than replacing the missing clotting factor, concizumab works by blocking TFPI, which is a natural inhibitor of the tissue factor pathway – the primary pathway for initiating blood coagulation. Under normal physiological conditions, when tissue is damaged, tissue factor (TF) is exposed and forms a complex with factor VIIa to initiate the coagulation cascade. TFPI normally limits this process by inhibiting both the TF/FVIIa complex and factor Xa. By blocking TFPI, concizumab enhances thrombin generation through the tissue factor pathway, effectively bypassing the need for factor VIII or factor IX. This mechanism makes Alhemo effective regardless of whether a patient has inhibitors against these clotting factors.

Alhemo is approved for the prevention and reduction of bleeding episodes (prophylaxis) in adults and adolescents aged 12 years and older with the following conditions:

• Hemophilia A with inhibitors: Patients who have developed antibodies (inhibitors) that block the activity of factor VIII replacement therapy.
• Severe hemophilia A without inhibitors: Patients whose blood levels of factor VIII are less than 1% of normal, who do not have inhibitors but require effective prophylaxis.
• Hemophilia B with inhibitors: Patients who have developed antibodies that block the activity of factor IX replacement therapy.
• Moderate to severe hemophilia B without inhibitors: Patients whose blood levels of factor IX are less than or equal to 2% of normal.

The efficacy of Alhemo has been demonstrated in the explorer clinical trial program, a series of phase 3 clinical trials that evaluated concizumab in patients with hemophilia A and B, both with and without inhibitors. These trials showed significant reductions in annualized bleeding rates compared to no prophylaxis, with many patients achieving zero or near-zero treated bleeds during the study period. The once-daily subcutaneous administration via a pre-filled pen offers a substantial improvement in treatment convenience compared to the frequent intravenous infusions required with traditional factor replacement or bypassing agent therapies.

What Should You Know Before Using Alhemo?

Contraindications

There is one absolute contraindication for the use of Alhemo: hypersensitivity (allergy) to concizumab or to any of the other ingredients in the product. The excipients include L-arginine hydrochloride, L-histidine, sodium chloride, sucrose, polysorbate 80, phenol, hydrochloric acid/sodium hydroxide (for pH adjustment), and water for injections. If you have experienced an allergic reaction to any of these substances previously, you must not use Alhemo.

Before starting treatment, your healthcare provider will perform a thorough assessment of your medical history, current medications, and overall health status to determine whether Alhemo is appropriate for you. This evaluation is particularly important because concizumab, by enhancing blood clotting, carries an inherent risk of causing unwanted blood clots (thrombotic events), especially in certain clinical situations.

Warnings and Precautions

There is a risk of allergic reactions with Alhemo, as with all monoclonal antibody therapies. Mild allergic reactions may present as skin rash, redness, hives, and itching. More severe allergic reactions (anaphylaxis) are possible and can be life-threatening. If you experience any signs of an allergic reaction, stop the injection and contact your doctor. If symptoms suggest a severe allergic reaction, seek emergency medical help immediately.

The risk of thrombotic events is a fundamental consideration with any therapy that enhances coagulation. Clinical trial data have shown that thrombotic events occurred uncommonly with Alhemo, but healthcare providers must carefully weigh the benefits of bleeding prevention against this risk. Patients should be educated about the signs and symptoms of blood clots and instructed to seek immediate medical attention if any occur. The risk may be increased during periods when additional hemostatic agents (factor concentrates or bypassing agents) are used to treat breakthrough bleeding episodes, and specific dosing guidelines for these situations must be followed precisely.

Pregnancy and Breastfeeding

The safety of Alhemo during pregnancy has not been established, and animal reproductive toxicity studies have not been conducted with concizumab. Since hemophilia is an X-linked condition that predominantly affects males, the use of Alhemo in pregnant women is an uncommon clinical scenario. However, female carriers of hemophilia may occasionally have low enough factor levels to require treatment. If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before using Alhemo.

It is not known whether concizumab passes into breast milk. Because monoclonal antibodies, including IgG, can be excreted in human milk, a risk to the breastfed infant cannot be excluded. Discuss with your healthcare provider whether to discontinue breastfeeding or discontinue Alhemo, taking into account the importance of the medicine for you and the potential risk to the child.

Women of childbearing potential should use a highly effective method of contraception during treatment with Alhemo and for at least 7 weeks after the last injection. Talk to your doctor about which type of contraception is most appropriate for you.

Driving and Operating Machinery

Alhemo is not expected to affect your ability to drive or operate machinery. No specific studies have been performed to evaluate the effect of concizumab on the ability to drive or use machines. However, if you experience any side effects that could affect your concentration or reaction time, you should refrain from driving or operating machinery until those effects have resolved.

Important Information About Ingredients

Alhemo contains less than 1 mmol (23 mg) of sodium per dose, meaning it is essentially sodium-free and is unlikely to have any effect on sodium-restricted diets. The product also contains 25 mg of polysorbate 80 per milliliter. Polysorbate is an excipient that can cause allergic reactions in susceptible individuals. Inform your doctor if you have any known allergies to polysorbate or have previously experienced reactions to medicines containing this ingredient.

How Does Alhemo Interact with Other Drugs?

Because Alhemo enhances blood coagulation by blocking TFPI, the most clinically significant interactions involve other medications that also promote clotting. The concurrent use of Alhemo with other procoagulant therapies requires careful management by your healthcare team to balance the need for effective hemostasis against the risk of excessive clotting (thrombosis). Tell your doctor about all medications you are using, have recently used, or might use, including over-the-counter products and supplements.

No formal drug interaction studies with conventional (non-hemostatic) medications have been conducted with concizumab. Because concizumab is a monoclonal antibody, it is not expected to be metabolized by cytochrome P450 enzymes or to interact with drugs that are substrates, inhibitors, or inducers of these enzymes. However, as with all new therapies, caution is advised when starting any new medication while on Alhemo.

Major Interactions

Minor Interactions

What Is the Correct Dosage of Alhemo?

Always use Alhemo exactly as your doctor has instructed. Your healthcare provider will determine the correct dose based on your body weight and individual response to treatment. Alhemo is injected subcutaneously (under the skin) into the abdomen or thigh using the pre-filled injection pen. The injection can be administered at any time of day, but it is important to maintain a consistent daily schedule. Before you begin self-injecting, you will receive thorough training from your doctor or nurse on the correct injection technique.

Adults and Adolescents (12 years and older)

The Alhemo pre-filled injection pen contains 15 mg of concizumab in 1.5 mL of solution (concentration: 10 mg/mL). The pen can deliver a maximum of 8 mg per injection. If your prescribed dose exceeds 8 mg, you will need to administer multiple injections. Your healthcare provider may prescribe a different pen size if available to allow your full daily dose in a single injection. Always use a new needle for each injection and perform a flow check before administering your dose.

Children Under 12 Years

Alhemo is not recommended for children under 12 years of age. The safety and efficacy of concizumab in this age group have not yet been established through clinical trials. Research is ongoing to evaluate the potential use of Alhemo in younger patients, and recommendations may be updated as new data become available. If your child has hemophilia, discuss alternative treatment options with their hematologist.

Elderly Patients

No specific dose adjustment is required for elderly patients based on age alone. However, elderly patients may have additional comorbidities (such as cardiovascular disease or impaired liver or kidney function) that could affect the risk-benefit profile of Alhemo. Your doctor will consider your overall health status when determining the appropriate dose and monitoring schedule. Because the risk of thrombotic events may be higher in older individuals, careful monitoring is particularly important in this population.

Missed Dose

Taking Alhemo consistently every day is important for maintaining its effectiveness. Missing doses can reduce the protection against bleeding. The steps for managing missed doses depend on when they occur during treatment:

• During the first 4 weeks of treatment: If you miss a dose during the initial phase, contact your doctor to discuss how to continue treatment. A missed dose during this critical period may require adjustments to your dosing regimen.
• After maintenance dose is established – 1 missed dose: Simply resume your regular daily dose the next day. Do not take a double dose to make up for the missed one.
• After maintenance dose is established – 2 to 6 missed doses: Take your daily dose twice (administered as two separate injections, each corresponding to one daily dose) on the day you resume treatment, then continue with your regular daily dose from the following day.
• 7 or more missed doses: Contact your doctor immediately, as you will need to receive a new loading dose before resuming your regular daily maintenance dose the following day.

Overdose

If you accidentally inject more Alhemo than prescribed, contact your doctor immediately. An overdose of concizumab could theoretically increase the risk of thrombotic events due to excessive inhibition of TFPI. Your healthcare provider will assess your condition and may perform blood tests to monitor coagulation parameters. There is no specific antidote for concizumab overdose; treatment would be supportive and based on clinical symptoms.

What Are the Side Effects of Alhemo?

Like all medicines, Alhemo can cause side effects, although not everyone will experience them. Most side effects are mild to moderate and tend to occur at the injection site. However, some side effects are serious and require immediate medical attention. It is important to be aware of the signs and symptoms of serious adverse events so that you can respond promptly.

Before listing the side effects by frequency, it is critical to emphasize that you should stop using Alhemo and contact your doctor immediately if you experience any symptoms suggesting a severe allergic reaction or blood clots, as described in the warnings section above. These are potentially life-threatening situations that require urgent medical evaluation.

Injection site reactions are the most frequently reported side effects with Alhemo. These reactions are generally mild and tend to improve over time as patients become accustomed to the daily injections. Rotating the injection site (choosing a new spot at least 5 centimeters from the previous injection site) can help minimize local reactions. If injection site reactions are persistent, severe, or worsening, inform your healthcare provider.

Allergic reactions have been observed in clinical trials and may range from mild skin reactions to more severe systemic responses. Your doctor should evaluate any allergic reaction to determine whether it is safe to continue treatment. In some cases, premedication with antihistamines may be considered for patients who have experienced mild allergic reactions.

Thrombotic events are the most clinically significant safety concern with Alhemo. These events are uncommon but can be serious. The risk may be increased when additional hemostatic agents are administered for breakthrough bleeding. Patients and caregivers must be thoroughly educated about the signs and symptoms of blood clots (described in the warnings section) and understand the importance of seeking immediate medical attention if they occur.

How Should You Store Alhemo?

Proper storage of Alhemo is essential to maintain the medicine’s effectiveness and safety. Concizumab, like all protein-based medicines, is sensitive to temperature extremes and must be handled according to the manufacturer’s instructions. Improper storage can degrade the active substance and potentially affect both efficacy and safety.

Before First Use

• Store unused Alhemo pre-filled pens in a refrigerator at 2°C to 8°C (36°F to 46°F).
• Keep the pen cap on at all times when not in use.
• Do not place the pen directly next to the cooling element inside the refrigerator, as this may cause freezing.
• Do not freeze Alhemo. If the medicine has been frozen, do not use it.
• Do not store at temperatures above 30°C (86°F).

After First Use (In-Use Storage)

Once you begin using an Alhemo pen, you have two storage options for the pen currently in use. The pen can be stored for a maximum of 28 days (4 weeks) from the date of first use, regardless of which storage method you choose:

• Refrigerator storage: Keep the pen at 2°C to 8°C. Do not place directly next to the cooling element. Do not use if the pen has been frozen.
• Room temperature storage: Keep the pen at temperatures below 30°C. Discard the pen if it has been exposed to temperatures above 30°C. Do not store in direct sunlight.

Always store the in-use pen with the pen cap on and without a needle attached. Attaching a needle during storage can lead to contamination, air bubbles, or medication leakage. Always use a new needle for each injection.

General Storage Instructions

• Keep Alhemo out of the sight and reach of children.
• Do not use the medicine after the expiry date printed on the label and carton (EXP). The expiry date refers to the last day of the indicated month.
• Do not use the medicine if the solution appears discolored. Alhemo should be a clear to slightly opalescent, colorless to slightly yellow solution. Translucent to white protein particles are acceptable.
• Dispose of used pens and needles safely according to the instructions of your healthcare provider, pharmacist, or local waste disposal guidelines. Do not dispose of medicines via wastewater or household waste.

What Does Alhemo Contain?

Understanding the full composition of Alhemo is important, particularly for patients who may have allergies or sensitivities to specific ingredients. The medicine is formulated as a sterile solution for subcutaneous injection, designed for stability and patient comfort during self-administration.

Active Ingredient

The active substance is concizumab. Each milliliter of Alhemo 15 mg/1.5 mL contains 10 mg of concizumab. Each pre-filled pen delivers 15 mg of concizumab in a total volume of 1.5 mL. Concizumab is a humanized immunoglobulin G4 (IgG4) monoclonal antibody produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells.

Inactive Ingredients (Excipients)

Appearance and Packaging

Alhemo is a clear to slightly opalescent, colorless to slightly yellow solution for injection in a pre-filled pen for single-patient use. Translucent to white particles of protein are acceptable and do not indicate a quality defect. Do not use the pen if the solution appears discolored or contains visible foreign particles beyond the acceptable protein particles described.

Alhemo 15 mg/1.5 mL is available as a single pack containing 1 pre-filled pen, or a multipack containing 5 pre-filled pens (5 packs of 1). Not all pack sizes may be marketed in all countries. Injection needles are not included and must be obtained separately. The pens are designed for use with NovoFine Plus 32G × 4 mm or NovoFine 32G × 4 mm needles, as recommended by your healthcare provider.

Marketing authorization holder and manufacturer: Novo Nordisk A/S, Novo Allé 1, DK-2880 Bagsværd, Denmark.