Marstacimab

Marstacimab has not been studied in patients with moderate or severe renal impairment.

Marstacimab has not been studied in patients with moderate or severe hepatic impairment.

Removal of TFPI inhibition may increase a patient’s coagulation potential and contribute to a patient’s individual, multifactorial risk for thromboembolic events. The following patients may be at an increased risk of thromboembolic events with use of this medicinal product:

• patients with a history of coronary artery disease, venous or arterial thrombosis or ischaemic disease,
• patients currently experiencing an acute severe illness with increased tissue factor expression (such as serious infection, sepsis, trauma, crush injuries, cancer).

Marstacimab has not been studied in patients with a history of previous thromboembolic events and there is limited experience in patients with acute severe illness.

The use of other anti-tissue factor pathway inhibitor (anti-TFPI) products has been associated with the development of thromboembolic complications in patients exposed to additional haemostatic agents (i.e. bypassing agents) in close proximity. No cases of thromboembolic events were observed in haemophilia patients who had received marstacimab prophylaxis in the clinical studies. Factor VIII and factor IX products have been safely administered for the treatment of breakthrough bleeds in patients receiving marstacimab. If factor VIII or factor IX products are indicated in a patient receiving marstacimab prophylaxis, the minimum effective dose of factor VIII or factor IX product according to the product label is recommended.

The benefit and risk of using marstacimab in patients with a history of thromboembolic events or currently experiencing an acute severe illness should be considered. Patients at risk should be monitored for early signs of thrombosis, and prophylaxis measures against thromboembolism should be instituted according to current recommendations and standard of care. Marstacimab prophylaxis should be interrupted if diagnostic findings consistent with thromboembolism occur and manage as clinically indicated.

There are no clinical studies of marstacimab use in pregnant women. Animal reproduction studies have not been conducted with marstacimab. It is not known whether marstacimab can cause foetal harm when administered to a pregnant woman or can affect reproduction capacity. Marstacimab should be used during pregnancy only if the potential benefit for the mother outweighs the risk to the foetus taking into account that, during pregnancy and after parturition, the risk for thrombosis is increased and that several pregnancy complications are linked to an increased risk for disseminated intravascular coagulation (DIC).

It is not known whether marstacimab is excreted in human milk. No studies have been conducted to assess the impact of marstacimab on milk production or its presence in breast milk. Human IgG is known to be excreted in breast milk during the first few days after birth, which is decreasing to low concentrations soon afterwards; consequently, a risk to the breast-fed infant cannot be excluded during this short period. Afterwards, marstacimab could be used during breast-feeding if clinically needed.

Women of childbearing potential

Women of childbearing potential receiving marstacimab should use effective contraception during, and for at least 1 month after cessation of marstacimab treatment.

Fertility

Animal studies do not indicate direct or indirect harmful effects with respect to fertility. No fertility data are available in humans. Thus, the effect of marstacimab on male and female fertility is unknown.

Marstacimab has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most frequently reported adverse reactions after treatment with marstacimab were injection site reactions (ISRs) (11.2%).

Tabulated list of adverse reactions

Safety data in the table below are based on pooled data from the Phase 3 safety and efficacy study (BASIS) and its open-label extension (OLE) study. The data from the pivotal Phase 3 study 12-month active treatment period reflects exposure of 116 male patients with haemophilia A or B without inhibitors to marstacimab administered once weekly. Ninety-seven (83.6%) patients were adults (18 years of age and older) and 19 (16.4%) were adolescents (12 years up to <18 years). At the time of data cut-off, a total of 87 of the 116 patients completing the 12-month treatment period subsequently enrolled in the OLE study. The median duration of exposure was 518.5 days (range 28 to 847 days).

The following table summarises the adverse reactions reported in patients who received marstacimab prophylaxis. The adverse reactions listed in the table below are presented by system organ class (SOC) and frequency categories, defined using the following convention: very common (≥1/10); common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000) or frequency not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Adverse reactions:

^a see 'Description of selected adverse reactions'

Description of selected adverse reactions

Injection site reactions

In total, 11.2% of patients treated with marstacimab reported ISRs. The majority of ISRs observed in marstacimab clinical studies were transient and reported as mild to moderate in severity. No occurrences of injection site reaction led to a dose adjustment or drug discontinuation. ISRs include injection site bruising, injection site erythema, injection site haematoma, injection site induration, injection site oedema, injection site pain, injection site pruritus, and injection site swelling.

Rash

In the non-inhibitor population, 0.9% of patients reported non-serious rash (Grade 1).

Paediatric population

The paediatric population studied comprises a total of 19 adolescent patients (from 12 to <18 years of age). The safety profile of marstacimab was overall consistent between adolescents and adults.