SOTATERCEPT-CSRK INJ,LYPHL

Clinical Criteria Summary

Care provided by a VA/VA Community Care provider experienced in the management of Pulmonary Arterial Hypertension (PAH)
World Health Organization (WHO) Group 1 PAH (idiopathic, heritable, drug-induced, connective tissue disease induced, or after shunt correction)
Definitive PAH confirmed by right-heart catheterization and hemodynamic diagnosis: mean pulmonary artery pressure greater than 20 mmHg, pulmonary capillary wedge pressure 15 mmHg or less, and pulmonary vascular resistance greater than 5 Wood units
WHO functional class II or III
On stable doses of background PAH therapy for at least 90 days
Risk factors for bleeding have been considered and addressed, including evaluating the continued need for use of drugs that increase bleeding risk (e.g., anticoagulants, NSAIDs, antiplatelets)

All patients of reproductive potential: Counseling provided on potential risk of fertility impairment
Patients who can become pregnant: Pregnancy should be excluded prior to receiving sotatercept. Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy and for 4 months after stopping treatment

Indicated for treatment of adults with pulmonary arterial hypertension (PAH) WHO Group 1 to increase exercise capacity, improve WHO functional class, and reduce risk of clinical worsening events.
Applicable PAH subtypes: idiopathic, heritable, drug-induced, connective tissue disease-associated, or after shunt correction.
Patients must be symptomatic (WHO functional class II or III) and on stable doses of PAH background therapy for at least 90 days.

Other Group 1 subtypes: PAH associated with HIV, portal-pulmonary disease, schistosomiasis, or veno-occlusive disease.
Platelet count <50,000/mm3.
Hepatic aminotransferase levels >3 times the upper limit of normal.

Available as lyophilized powder for injection in single-use vials (45 mg and 60 mg).
Starting dose: 0.3 mg/kg by subcutaneous (SC) injection once every 3 weeks.
Target dose: 0.7 mg/kg SC once every 3 weeks.
Store in refrigerator until ready for use.
Administered as a weight-based subcutaneous injection; requires laboratory monitoring of platelets and hemoglobin.

Check hemoglobin and platelet counts prior to each dose for the first 5 doses (or longer if values are unstable).
Delay treatment for at least 3 weeks if any of the following occur:
Hemoglobin increased >2.0 g/dL from previous dose and is above ULN
Hemoglobin increased >4.0 g/dL from baseline
Hemoglobin increased >2.0 g/dL above ULN
Platelet count decreased to <50,000/mm3

No boxed warnings or contraindications stated.
Erythrocytosis: Increased hemoglobin >2g/dL above ULN occurred in 15% of patients; severe erythrocytosis may increase risk of thromboembolic events or hyperviscosity syndrome.
Thrombocytopenia: Platelet counts <50,000/mm3 seen in 3% of patients (all receiving epoprostenol).
Serious bleeding: Increased bleed risk observed; serious bleeding more likely with prostacyclin therapy, antithrombotics, or low platelet count. Excess bleeding primarily epistaxis and gingival bleeding.
Adverse reactions occurring in >10% of patients: Headache, epistaxis, rash, telangiectasia, diarrhea, dizziness, erythema.

Embryo-fetal toxicity: May cause fetal harm; advise use of effective contraception during treatment and for at least 4 months after stopping.
Impaired fertility: May impair fertility in females and males.

No difference in efficacy between patients <65 years and ≥65 years.
More bleeding events observed in older vs younger subgroups.
Insufficient numbers of patients aged 75 years and older to evaluate efficacy and safety.