Hemlibra (Emicizumab)

What Is Hemlibra and What Is It Used For?

Hemlibra (emicizumab) is a bispecific monoclonal antibody prescribed for routine prophylaxis of bleeding episodes in patients of all ages with hemophilia A. It is indicated both for patients who have developed inhibitory antibodies against factor VIII and for those with severe or moderate hemophilia A without inhibitors who have a severe bleeding phenotype.

Hemlibra contains the active substance emicizumab, which belongs to a class of medicines known as monoclonal antibodies. Monoclonal antibodies are a type of protein designed to recognise and bind to specific targets in the body. What makes Hemlibra unique is that it is bispecific – meaning it can simultaneously bind to two different targets at once. Specifically, emicizumab binds to both activated factor IX (FIXa) and factor X (FX), bringing them together in a way that mimics the natural cofactor function of activated factor VIII (FVIIIa).

Hemophilia A is an inherited bleeding disorder caused by a deficiency or absence of coagulation factor VIII (FVIII), a protein essential for normal blood clotting. Without adequate FVIII, the blood cannot clot properly, leading to prolonged and sometimes spontaneous bleeding episodes. These bleeds can occur into joints (hemarthrosis), muscles, and internal organs, causing pain, swelling, and over time, irreversible joint damage known as hemophilic arthropathy. The severity of hemophilia A is classified by the level of FVIII activity in the blood: severe (<1%), moderate (1–5%), and mild (5–40%).

Hemlibra is indicated for use in the following patient populations:

• Patients with FVIII inhibitors: Some patients with hemophilia A develop inhibitory antibodies (inhibitors) against replacement factor VIII, rendering standard FVIII treatment ineffective. Hemlibra provides an alternative approach because its molecular structure is completely different from FVIII and is therefore not neutralised by these inhibitors.
• Patients without inhibitors with severe hemophilia A: Patients whose blood FVIII levels are less than 1% of normal.
• Patients without inhibitors with moderate hemophilia A and a severe bleeding phenotype: Patients whose FVIII levels are 1–5% of normal but who experience frequent or clinically significant bleeding episodes.

The primary goal of Hemlibra treatment is prophylaxis – the prevention of bleeding episodes rather than the treatment of acute bleeds. In the landmark HAVEN clinical trial program (HAVEN 1 through HAVEN 7), emicizumab demonstrated statistically significant and clinically meaningful reductions in annualised bleeding rates across all patient populations studied. In HAVEN 1, which enrolled adults and adolescents with FVIII inhibitors, emicizumab prophylaxis reduced bleeding rates by 87% compared to no prophylaxis. In HAVEN 3, which studied patients without inhibitors, emicizumab reduced bleeding rates by 68% compared to prior factor VIII prophylaxis.

What Should You Know Before Using Hemlibra?

Do not use Hemlibra if you are allergic to emicizumab or any other ingredient. Before starting treatment, inform your doctor about all medicines you take, especially bypassing agents such as aPCC and rFVIIa. Concurrent use of aPCC with Hemlibra has caused life-threatening thrombotic microangiopathy and blood clots.

Contraindications

You must not use Hemlibra if you are allergic (hypersensitive) to emicizumab or any of the other ingredients in the solution. The excipients include L-arginine, L-histidine, L-aspartic acid, poloxamer 188, and water for injections. If you are uncertain whether you have an allergy to any component, consult your doctor or pharmacist before using this medicine.

Warnings and Precautions

Before you start using Hemlibra, it is essential to discuss with your doctor the use of medicines that have factor VIII inhibitor bypassing activity, known as “bypassing agents” (medicines that help the blood to clot but work in a different way from factor VIII). This is critically important because treatment with certain bypassing agents may need to be changed while you are receiving Hemlibra. Examples of such medicines include activated prothrombin complex concentrate (aPCC) and recombinant factor VIIa (rFVIIa).

Use of bypassing agents during Hemlibra treatment: Hemlibra increases the ability of your blood to clot. Therefore, the dose of bypassing agent required may be lower than the dose you used before starting Hemlibra. Use aPCC only if no other treatment options are available. If aPCC is necessary, speak to your doctor if you feel you need a total of more than 50 units/kg of aPCC. Although experience is limited, you should also be aware that there is a risk of thromboembolic events when antifibrinolytics (medicines that promote clotting, such as tranexamic acid or aminocaproic acid) are given intravenously in combination with aPCC or rFVIIa in patients receiving Hemlibra.

Antibody Formation (Immunogenicity)

In some patients, the body may develop antibodies against emicizumab that can reduce the effectiveness of the medicine. You may notice that bleedings cannot be controlled with your prescribed dose. If you or your caregiver observe an increase in bleeding episodes, contact your doctor immediately. Your doctor may decide to change your treatment if Hemlibra is no longer working for you.

Children Under 1 Year of Age

In children younger than 1 year, the blood coagulation system is still developing. If your child is younger than 1 year, your doctor will only prescribe Hemlibra after carefully weighing the expected benefits against the risks of using this medicine.

Laboratory Tests

Tell your doctor if you are using Hemlibra before you have any blood tests to measure how well your blood clots. Because Hemlibra mimics FVIII activity, it can interfere with certain coagulation laboratory tests, potentially leading to inaccurate results. Affected tests include the activated partial thromboplastin time (aPTT), aPTT-based one-stage FVIII activity assays, and some aPTT-based factor assays. Chromogenic FVIII activity assays using bovine reagents and thrombin time-based assays are not affected.

Pregnancy and Breastfeeding

You should use an effective method of contraception during treatment with Hemlibra and for 6 months after your last injection. If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine. Your doctor will consider the benefits of taking Hemlibra against the risks to your child.

Driving and Operating Machinery

Hemlibra is not expected to affect your ability to drive a vehicle or operate any tools or machinery.

How Does Hemlibra Interact with Other Drugs?

The most critical drug interactions with Hemlibra involve bypassing agents, particularly activated prothrombin complex concentrate (aPCC). Concurrent use of aPCC with Hemlibra has caused thrombotic microangiopathy and thromboembolism. The dose of bypassing agents may need to be reduced. Antifibrinolytics used with aPCC or rFVIIa also carry additional clotting risk.

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines. The most important interactions concern medicines used to manage hemophilia A, specifically bypassing agents and factor VIII concentrates. Because Hemlibra increases the blood’s clotting ability, the interaction with additional pro-haemostatic agents can shift the haemostatic balance dangerously towards excessive clotting.

Critical Interactions with Bypassing Agents

What Is the Correct Dosage of Hemlibra?

Hemlibra dosing is weight-based. All patients start with a loading dose of 3 mg/kg once weekly for 4 weeks. After this, the maintenance dose is either 1.5 mg/kg weekly, 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks, as decided by the prescribing physician. The maximum volume per injection is 2 mL.

Hemlibra is supplied as a ready-to-use solution in single-use vials and does not require reconstitution or dilution. Treatment should be initiated and supervised by a physician experienced in the management of hemophilia. Always use this medicine exactly as your doctor has told you. Check with your doctor, pharmacist, or nurse if you are unsure.

Loading Dose (Weeks 1–4)

Maintenance Dose (From Week 5 Onward)

After completing the 4-week loading phase, one of the following maintenance regimens is selected in consultation with your physician:

The choice of maintenance regimen should be made in consultation with your physician and, if applicable, your caregiver. Different Hemlibra concentrations (30 mg/mL and 150 mg/mL) must not be combined in the same injection when preparing the total volume. The maximum volume of Hemlibra solution per single injection is 2 mL. If the prescribed dose requires more than 2 mL, it must be divided into separate injections at different injection sites.

Children and Adolescents

Hemlibra can be used in adolescents and children of all ages, including newborns. The dosing regimen (loading and maintenance doses) is the same as for adults, calculated based on the child’s body weight. A child may self-inject this medicine provided that the child’s healthcare provider and parent or caregiver agree. Self-injection is not recommended for children under 7 years of age.

Missed Dose

If you forget to take your scheduled injection, inject the missed dose as soon as possible before the day of your next scheduled dose. Then continue injecting the medicine as scheduled. Do not inject two doses on the same day to make up for a missed dose. If you are unsure what to do, ask your doctor, pharmacist, or nurse.

Overdose

If you use more Hemlibra than you should, tell your doctor immediately. This is important because you may be at increased risk of developing side effects such as blood clots. Always use Hemlibra exactly as your doctor has instructed.

Stopping Treatment

Do not stop using Hemlibra without first talking to your doctor. If you stop using Hemlibra, you may no longer be protected against bleeding. Emicizumab has a long half-life of approximately 4–5 weeks, meaning the drug remains in your body for some time after discontinuation, and you should discuss with your doctor when it is safe to resume alternative prophylactic therapy.

How Should Hemlibra Be Administered?

Hemlibra is given as a subcutaneous injection (under the skin). After training from a healthcare provider, patients or caregivers can administer injections at home. Recommended injection sites include the lower abdomen, outer upper arms, or front of the thighs. Rotate injection sites and use a new needle for each injection.

Hemlibra is supplied as a clear, colourless to slightly yellow ready-to-use solution in single-use glass vials. Before use, take the vial out of the refrigerator approximately 15 minutes before the injection and allow it to reach room temperature (below 30°C). Do not try to warm it in any other way. Do not shake the vial. Check that the solution does not contain particles, is not cloudy, and is not discoloured before use.

Preparing the Injection

The solution is drawn up from the vial into a syringe using either a transfer needle with a 5-micrometre filter or a vial adapter with a 5-micrometre filter. The filter is essential to remove any potential particles. You will then replace the transfer device with an injection needle (26 gauge, or an acceptable range of 25–27 gauge) for subcutaneous administration. Syringes, transfer needles/adapters, and injection needles are not included in the Hemlibra package and must be obtained separately.

• For injections up to 1 mL: Use a 1 mL syringe with 0.01 mL graduations
• For injections between 1 mL and 2 mL: Use a 2–3 mL syringe with 0.1 mL graduations
• Do not use a 2–3 mL syringe for doses up to 1 mL

Recommended Injection Sites

The recommended areas for subcutaneous injection are:

• Front of the waist (lower abdomen), avoiding the area 5 cm around the navel
• Outer upper arm (only if given by another person)
• Front of the thighs

For each injection, use a different area from the one used previously, at least 2.5 cm from any previous injection site. Do not inject into areas where the skin is red, bruised, tender, hard, or has birthmarks or scars. Pinch a fold of skin at the cleaned injection site to ensure the needle goes into the fatty tissue beneath the skin, not into muscle. Insert the needle at a 45–90 degree angle and inject slowly.

After the Injection

If you see blood drops at the injection site, press a sterile cotton ball or gauze over the site for at least 10 seconds until bleeding stops. If bruising occurs, an ice pack can be gently applied. Do not rub the injection site. Dispose of all used needles, syringes, and vials in a sharps disposal container immediately after use.

What Are the Side Effects of Hemlibra?

The most common side effects of Hemlibra are injection site reactions (redness, itching, pain), headache, and joint pain. The most serious side effects – thrombotic microangiopathy and thromboembolism – have occurred when aPCC was used concurrently. Stop treatment and seek immediate medical attention if you experience symptoms of TMA or blood clots.

Like all medicines, Hemlibra can cause side effects, although not everybody gets them. The safety profile of Hemlibra has been extensively evaluated in the HAVEN clinical trial program and through ongoing post-marketing surveillance. The most serious adverse events are associated with the concurrent use of aPCC bypassing agent.

Reporting side effects: If you experience any side effects, including those not listed here, talk to your doctor, pharmacist, or nurse. You can also report side effects directly through your national adverse drug reaction reporting system (e.g., the Yellow Card Scheme in the UK, MedWatch in the US, or corresponding agencies in your country). By reporting side effects, you can help provide more information on the safety of this medicine.

How Should You Store Hemlibra?

Store unopened Hemlibra vials in a refrigerator at 2–8°C. Do not freeze. Keep in the original packaging to protect from light. Unopened vials may be kept at room temperature (below 30°C) for up to 7 days. Once drawn into a syringe, the solution must be used immediately.

Proper storage of Hemlibra is essential to maintain the medicine’s effectiveness and safety. Follow these storage guidelines carefully:

• Refrigeration: Store vials in a refrigerator at 2–8°C (36–46°F). Do not freeze. If a vial has been accidentally frozen, do not use it – dispose of it appropriately.
• Light protection: Keep vials in the original carton to protect from light.
• Room temperature storage: Unopened vials that have been removed from the refrigerator may be stored at room temperature (at or below 30°C / 86°F) for up to 7 days. After room temperature storage, they can be returned to the refrigerator. The total cumulative time outside the refrigerator must not exceed 7 days.
• Dispose of exposed vials: Discard any vials that have been stored at room temperature for more than 7 days or that have been exposed to temperatures above 30°C.
• Use after drawing up: Once Hemlibra solution has been transferred from the vial to the syringe, it must be used immediately. Do not refrigerate the filled syringe.
• Check before use: Before each use, inspect the solution. It should be colourless to slightly yellow. Do not use if the solution is cloudy, discoloured, or contains visible particles.
• Single-use only: Each vial is for single use. Discard any unused solution remaining in the vial after your injection.
• Expiry date: Do not use after the expiry date printed on the carton and vial label (EXP). The expiry date refers to the last day of the stated month.
• Keep out of reach of children.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures help to protect the environment.

What Does Hemlibra Contain?

Each vial of Hemlibra contains emicizumab as the active substance at a concentration of 30 mg/mL or 150 mg/mL. The vials contain 12 mg (0.4 mL), 30 mg (1 mL), 60 mg (0.4 mL), 105 mg (0.7 mL), or 150 mg (1 mL) of emicizumab. Inactive ingredients include L-arginine, L-histidine, L-aspartic acid, poloxamer 188, and water for injections.

Active Substance

The active substance is emicizumab, a humanised bispecific monoclonal antibody produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells. Hemlibra is available in two concentrations:

Inactive Ingredients (Excipients)

• L-arginine
• L-histidine
• L-aspartic acid
• Poloxamer 188
• Water for injections

Appearance

Hemlibra is a clear, colourless to slightly yellow solution for injection. Each pack contains 1 single-use glass vial. Not all pack sizes or concentrations may be marketed in all countries.

Manufacturer

Hemlibra is manufactured by Roche Pharma AG, Emil-Barell-Strasse 1, 79639 Grenzach-Wyhlen, Germany. The marketing authorisation holder is Roche Registration GmbH, Emil-Barell-Strasse 1, 79639 Grenzach-Wyhlen, Germany.

Frequently Asked Questions About Hemlibra