WINREVAIR Powder and solvent for solution for injection Ref.[114917] Active ingredients: Sotatercept

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Erythrocytosis

Increases in Hgb have been observed in patients during treatment with sotatercept. Severe erythrocytosis may increase the risk of thromboembolic events and hyperviscosity syndrome. Use caution in patients with erythrocytosis who are at increased risk of thromboembolic events. Hgb should be monitored before each dose for the first 5 doses, or longer if values are unstable, and every 3 to 6 months thereafter to determine if dose adjustments are required (see sections 4.2 and 4.8). If a patient develops erythrocytosis, HCP should consider re-evaluating the patient’s or caregiver’s administration technique.

Severe thrombocytopenia

Decreased platelet count has been observed in some patients taking sotatercept including severe thrombocytopenia (platelet count <50 × 10⁹/L). Thrombocytopenia was reported more frequently in patients also receiving prostacyclin infusion (21.5%) compared to patients not receiving prostacyclin infusion (3.1%) (see section 4.8). Severe thrombocytopenia may increase the risk of bleeding events. Platelet count should be monitored before each dose for the first 5 doses, or longer if values are unstable, and every 3 to 6 months thereafter to determine whether dose adjustments are required (see section 4.2).

Serious bleeding

In clinical studies, serious bleeding events (including gastrointestinal, intracranial haemorrhage) have been observed in 4.3% of patients during treatment with sotatercept (see section 4.8). Patients with serious bleeding events were more likely to be on prostacyclin background therapy and/or antithrombotic agents, have low platelet count, or be 65 years of age or older. Patients should be advised about any signs and symptoms of blood loss. A physician should evaluate and treat bleeding events accordingly. Sotatercept should not be administered if the patient is experiencing a serious bleeding event.

Limitation of the clinical data

The clinical studies did not include participants with human immunodeficiency virus (HIV), portal hypertension, schistosomiasis-, or pulmonary veno occlusive disease (PVOD)-associated PAH.

Excipients with known effect

This medicinal product contains le ss than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium free’.

This medicinal product contains 0.20 mg of polysorbate 80 in each mL of reconstituted solution. Polysorbates may cause allergic reactions.

No interaction studies have been performed

Women of childbearing potential

Pregnancy testing is recommended for women of childbearing potential before starting treatment. Women of childbearing potential should use effective contraception during treatment and for at least 4 months after the last dose if treatment is discontinued (see section 5.3).

Pregnancy

There are no data from the use of sotatercept in pregnant women. Studies in animals have shown reproductive toxicity (increases in post-implantation losses, reduction in foetal body weights, and delays in ossification) (see section 5.3).

Winrevair is not recommended during pregnancy and in women of childbearing potential not using contraception.

Breast-feeding

It is unknown whether sotatercept/metabolites are excreted in human milk. A risk to newborns/infants cannot be excluded.

Breast-feeding should be discontinued during treatment and for 4 months after the last dose of treatment.

Fertility

Based on findings in animals, sotatercept may impair female and male fertility (see section 5.3).

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

Summary of safety profile

The most frequently reported adverse reactions were headache (24.5%), epistaxis (22.1%), telangiectasia (16.6%), diarrhoea (15.3%), dizziness (14.7%), rash (12.3%), and thrombocytopenia (10.4%).

The most frequently reported serious adverse reactions were thrombocytopenia (<1%) and epistaxis (<1%).

The most common adverse reactions leading to discontinuation were epistaxis and telangiectasia.

Tabulated list of adverse reactions

The safety of sotatercept was evaluated in the pivotal study STELLAR, a placebo-controlled study of 163 patients with PAH treated with sotatercept (see section 5.1). The median duration of treatment with sotatercept was 313 days.

The adverse reactions reported with sotatercept are listed in the table below by MedDRA system organ class and by frequency. Frequencies are defined as 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), and very rare (<1/10 000).

Table 3. Adverse reactions:

¹ See description of selected adverse reactions
² Includes ‘thrombocytopenia’ and 'platelet count decreased'
³ Includes ‘hypertension’, ‘blood pressure diastolic increased’ and 'blood pressure increased'

Description of selected adverse reactions

Increased haemoglobin

In STELLAR, adverse reactions of i ncreased Hgb (‘haemoglobin increased’ and ‘polycythaemia’) were reported in 8.6% of patients taking sotatercept. Based on laboratory data, m oderate elevations in Hgb (>1.24 mmol/L (2 g/dL) above ULN) occurred in 15 .3% of patients taking sotatercept. Increases in Hgb were managed by dose adjustments (see sections 4.2 and 4.4).

Thrombocytopenia

Thrombocytopenia (‘thrombocytopenia’ and ‘platelet count decreased’) was reported in 10.4% of patients taking sotatercept. Severe reduction in platelet count <50 × 10⁹/L occurred in 2.5% of patients taking sotatercept. Thrombocytopenia was reported more frequently in patients also receiving prostacyclin infusion (21.5%) compared to patients not receiving prostacyclin infusion (3.1%). Thrombocytopenia was managed by dose adjustments (see sections 4.2 and 4.4).

Telangiectasia

Telangiectasia was observed in 16.6% of patients taking sotatercept. The median time to onset was 18.6 weeks. Discontinuations of treatment due to telangiectasia were 1% in the sotatercept group.

Increased blood pressure

Increased blood pressure was reported in 4.3% of patients taking sotatercept. In patients taking sotatercept, mean systolic blood pressure increased from baseline by 2.2 mmHg and diastolic blood pressure increased by 4.9 mmHg at 24 weeks.

Elderly

With the exception of bleeding events (a collective group of adverse events of clinical interest), there were no differences in safety between the <65-year-old and ≥65-year-old subgroups. Bleeding events occurred more commonly in the older sotatercept subgroup (52% vs 31.9% in patients <65-year-old); however, there was no notable imbalance between age cate gories for any specific bleeding event. Serious bleeding occurred in 3.6% of patients <65-year-old and in 8.0% of patients ≥65-year-old taking sotatercept.

Long-term safety data

Long-term safety data are available from pooled phase 2 and phase 3 clinical studies (n=431). The median duration of exposure was 657 days. The safety profile was generally similar to that observed in the pivotal STELLAR study.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactio ns via the national reporting system listed in Appendix V.

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.