Alhemo (concizumab-mtci) for hemophilia

Last updated Jan. 8, 2025, by Lindsey Shapiro, PhD
Fact-checked by Joana Carvalho, PhD

What is Alhemo for hemophilia?

Alhemo (concizumab-mtci) is an antibody-based therapy that’s approved in the U.S. to prevent or reduce the frequency of bleeds in people with hemophilia A or B who have inhibitors, or neutralizing antibodies targeting the clotting factor they are missing.

Developed and marketed by Novo Nordisk, Alhemo is administered via daily under-the-skin, or subcutaneous, injections that can be self-administered by patients or given by caregivers after proper training.

Therapy snapshot

How does Alhemo work?

People with hemophilia lack certain blood clotting proteins, making them vulnerable to excessive, prolonged, or spontaneous bleeding episodes. Specifically, hemophilia A patients lack a clotting protein called factor VIII, or FVIII, while those with hemophilia B lack factor IX, or FIX.

Standard preventive (prophylactic) treatment for hemophilia often involves factor replacement therapy to provide patients with a version of FVIII or FIX. However, some patients’ immune systems will mistakenly identify these proteins as a threat, and develop antibodies called inhibitors to attack them, making the treatment less effective.

Alhemo is an antibody-based therapy that’s designed to block the activity of the tissue factor pathway inhibitor (TFPI) protein. TFPI normally interferes with the initial steps that lead to the production of thrombin, an enzyme critical for blood clotting. By inhibiting TFPI, Alhemo increases the production of thrombin, thereby facilitating blood clotting and preventing bleeds in people with hemophilia. Because it works by a different mechanism that doesn’t rely on FVIII or FIX, Alhemo can be used in people with inhibitors.

Who can take Alhemo?

Alhemo was approved by the U.S. Food and Drug Administration (FDA) in December 2024 as a routine prophylactic therapy to prevent or reduce the frequency of bleeds in people with hemophilia A or B, ages 12 and older, with inhibitors. With the approval, Alhemo became the first subcutaneous treatment of its kind to be approved for this specific patient population.

The therapy is similarly approved in other regions, including the European Union, as well as in Canada, Australia, and Switzerland. In Japan, it’s approved for patients with hemophilia A and B, ages 12 and older, with or without inhibitors.

Who should not take Alhemo?

Alhemo is contraindicated, or not recommended, to patients with a history of serious allergic reactions to the medication or any of its ingredients.

How is Alhemo administered?

Alhemo is given via daily subcutaneous injections that can be self-administered by patients or given by caregivers after proper training from a healthcare provider. It comes in premixed, prefilled injection pens in the following concentrations:

• 60 mg/1.5 mL (40 mg/mL), brown label
• 150 mg/1.5 mL (100 mg/mL), gold label
• 300 mg/3 mL (100 mg/mL), white label.

Alhemo is administered at an individualized maintenance dose based on the concentration of the medication’s active ingredient in a person’s bloodstream measured four weeks, or about one month, after starting treatment. Before that measurement, Alhemo should be administered as follows:

• a loading dose of 1 mg/kg of body weight on the first day of treatment
• a once-daily dose of 0.2 mg/kg until the individual maintenance dose is selected.

Individualized maintenance dosing should be initiated once Alhemo concentrations have been measured in the blood, and no later than eight weeks, or about two months, after treatment has been started. Dose selection should be based on Alhemo blood concentrations, as follows:

• less than 200 nanograms per milliliter (ng/mL), adjust to a daily dose of 0.25 mg/kg
• 200 to 4,000 ng/mL, continue at a daily dose of 0.2 mg/kg
• greater than 4,000 ng/mL, adjust to daily dose of 0.15 mg/kg.

The therapy’s blood concentration should be routinely measured in patients who have been on the same maintenance dose for eight weeks to ensure that it remains above 200 ng/mL. If the therapy’s blood concentration is lower than 200 ng/mL in two consecutive measurements, the benefits of treatment and the potential risk of bleeding should be reconsidered. Alternative treatments may also be considered in such cases.

Alhemo injection pens are designed to be used with 32 gauge NovoFine or NovoFine Plus needles that are 4 mm in length, which are sold separately. A new needle should be used for each injection, and Alhemo pens should not be shared between patients, even if the needle is changed.

Injections are given into the thigh or abdomen, and the injection site should be rotated daily. Injections should not be given in areas where the skin is tender, bruised, red or hard, or in areas where there are moles, scars, or stretch marks.

Prior to the first use, Alhemo should be stored in the refrigerator. After the first use, Alhemo can be stored in the fridge or at room temperature for up to 28 days, or approximately four weeks. Any unused portion should be discarded thereafter. Alhemo should always be stored with the cap on and in its original carton to protect it from light. It should be kept away from direct heat and sunlight and should never be frozen.

Patients should inform their healthcare provider right away if they miss a dose of Alhemo during the first month of treatment, as the dosing regimen may need to be adjusted. If a dose is missed after the maintenance dose is established, the following guidelines should be followed:

• for one missed dose, continue the normal daily dosing regimen
• for 2-6 missed doses, take a double dose as soon as possible and then continue the normal daily dose the next day
• for seven or more missed doses, contact a healthcare provider as soon as possible, as a new loading dose may be necessary before continuing daily treatment.

The dose of Alhemo does not need to be adjusted if breakthrough bleeds occur or around the time of any minor surgery. Before a major surgery, the patient’s doctor will advise whether Alhemo needs to be paused for some time before the procedure.

When switching to Alhemo from other hemophilia therapies, certain treatments may need to be stopped for a certain amount of time beforehand. Patients should talk with their healthcare team about when and if it is appropriate to discontinue any other treatments. They also should discuss with their doctors the appropriate use of bypassing agents to treat any breakthrough bleeds while on Alhemo.

Alhemo in clinical trials

Alhemo’s safety and proof-of-concept efficacy were first established in the Novo Nordisk-sponsored Phase 2 explorer4 (NCT03196284) and explorer5 (NCT03196297) studies, involving patients with and without inhibitors, respectively. The benefits of the treatment were then confirmed in the Phase 3 explorer7 (NCT04083781) and explorer8 (NCT04082429) trials, also respectively involving patients with and without inhibitors.

Explorer7 and explorer8 were temporarily paused by the FDA in 2020 after three people who received Alhemo in the trials experienced blood clotting events. The studies were later resumed with updated protocols and a new dose adjustment regimen.

Explorer7 trial

Alhemo’s U.S. approval was based largely on data from explorer7, which enrolled 133 males with hemophilia A or B, ages 12 and older, with inhibitors.

The main efficacy analysis involved a group of participants who had been receiving on-demand treatment with bypassing agents. These patients were randomly assigned to either continue receiving on-demand treatment without prophylaxis for at least 24 weeks, or about six months — dubbed group 1 — or to receive Alhemo prophylaxis for at least 32 weeks, or slightly longer than seven months. This second cohort was named group 2.

Two additional groups of trial participants also were enrolled. Among them were those who had received Alhemo in explorer4, patients who had received prophylaxis with a bypassing agent, and additional patients taking on-demand treatment. All received Alhemo.

The study’s main goal was to compare the estimated mean annualized bleed rate, or ABR — the mean number of bleeds occurring per year — for spontaneous and traumatic bleeds requiring treatment between groups 1 and 2.

The results showed the estimated mean ABR for treated spontaneous and traumatic bleeds was 11.8 among patients in group 1 and 1.7 in group 2, amounting to an 86% bleed reduction with Alhemo. Rates of all bleeding episodes, including treated and untreated bleeds, were similarly lower in the Alhemo group. Across all patients who received Alhemo, the median ABR for treated spontaneous and traumatic bleeds was zero, compared with 9.8 in patients not on prophylaxis. Patient-reported outcome measures favored Alhemo in some measures of life quality, treatment burden, and patient treatment preferences.

An open-label extension phase of explorer7 is ongoing; all participants are receiving Alhemo for up to about five years.

Explorer8 trial

The similarly designed explorer8 trial tested Alhemo in patients ages 12 and older without inhibitors. It enrolled 148 people with severe hemophilia A or moderate to severe hemophilia B who had been treated with replacement therapies in the six months before study screening.

As in explorer7, the study’s main goal was to compare the number of treated spontaneous and traumatic bleeds among patients who had been randomly assigned to continue on-demand factor therapy without prophylaxis for at least 24 weeks, or to receive Alhemo prophylaxis for at least 32 weeks.

Two additional groups of patients, including individuals who participated in explorer5, had enrolled before the trial’s pause, or who had received previous prophylaxis in the observational explorer6 study (NCT03741881), were enrolled and received Alhemo.

In the study, the estimated mean ABR for treated spontaneous and traumatic bleeds was reduced by 86% with Alhemo compared with the no prophylaxis group in people with hemophilia A, and by 79% in individuals with hemophilia B, the results showed.  Among those with hemophilia A, the median ABR while on Alhemo was 2.9 compared with 19.6 without prophylaxis. For those with hemophilia B, the median ABR was 1.6 with Alhemo and 14.9 without it.

An open-label extension phase of explorer8 is ongoing in which all participants are receiving Alhemo for up to about five years.

Other ongoing trials

An open-label Phase 3 trial called Explorer10 (NCT05135559) is further testing Alhemo’s safety and efficacy in approximately 90 people with severe hemophilia A or moderate to severe hemophilia B, with or without inhibitors. Its main goal is to evaluate the treatment’s effects on the number of treated spontaneous and traumatic bleeds. Explorer10 is expected to finish in late 2029.

Common side effects of Alhemo

The most common side effects of Alhemo reported in hemophilia patients include:

• injection site reactions
• hives, or urticaria.

Blood Clots

Alhemo may increase the risk of thromboembolic or blood clotting-related events, especially in people with other risk factors for thromboembolism. Risk factors include the use of high or frequent doses of on-demand treatments for breakthrough bleeds, or conditions in which the tissue factor protein is at higher than normal levels, such as atherosclerotic disease, crush injury, cancer, disseminated intravascular coagulation, thrombotic microangiopathy, or septicemia.

Patients should be monitored for signs of blood clots. If a blood clot is suspected, Alhemo should be discontinued.

Alhemo can also lead to increased levels of fibrin D-dimer and prothrombin fragment 1.2, which are two biomarkers used to identify blood clots. As such, these markers may not be reliable for predicting the presence of blood clots in people on Alhemo.

Allergic reactions

Alhemo may cause allergic reactions, including redness, rash, itching, or abdominal pain. In rare cases, its use could lead to anaphylaxis, a life-threatening allergic reaction. Patients should contact their healthcare providers if they experience mild reactions, and seek urgent medical attention for moderate or severe reactions. If a severe allergic reaction occurs, Alhemo should be discontinued and medical management initiated.

Use in pregnancy and breastfeeding

No clinical studies have investigated Alhemo’s use in pregnant women, but based on its mechanism of action, and the fact that it can pass through the placenta, it is believed the treatment may cause harm to a developing fetus if administered during pregnancy. Alhemo should only be used during pregnancy if the potential benefits for the mother outweigh the potential risks to the fetus.

Pregnancy testing is recommended before starting Alhemo for women of reproductive potential. Such patients should also use a highly effective form of contraception during treatment and for seven weeks after ending treatment.

There is no information on whether Alhemo passes into breast milk or has an effect on nursing infants. However, antibodies in the same class as Alhemo are known to be excreted, or pass, into the breast milk during the first few days after birth. Alhemo can be used after this initial period if clinically needed.

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