Safety Profile

Safety Profile

The following data reflect exposure to WINREVAIR in the pivotal STELLAR trial.

• After completing the primary 24-week treatment phase, patients continued into a long-term double-blind (LTDB) treatment period, maintaining their current therapy, until all patients completed the primary treatment period.
• The median durations of treatment were similar between the placebo and WINREVAIR groups (229.5 days vs 252.0 days, respectively).

Adverse reactions occurring in STELLAR by the time all patients completed the primary 24-week period of the study are summarized below.

Adverse reactions in patients receiving WINREVAIR (DBPC + LTDB)^a:

^aDouble-blind placebo-controlled period + long-term double-blind period.
^bComposite terms.

Increased hemoglobin

The majority of events of increased hemoglobin (Hgb increased, polycythemia) were non-serious, mild, and reversible, and were not associated with discontinuation of therapy.

• Moderate elevations in Hgb (>2 g/dL above upper limit of normal [ULN]) occurred in 12.3% of patients taking WINREVAIR.
• No severe elevations (≥4 g/dL above ULN) were observed.
• Increases in Hgb were manageable by dose delays, dose reductions, or both.

Thrombocytopenia

The majority of events of thrombocytopenia (thrombocytopenia and platelet count decreased) were non-serious, mild, reversible, and have not been associated with discontinuation of therapy.

• Severe reduction in platelet count <50,000/mm³ (<50.0 x 10⁹/L) occurred in 1.8% of patients taking WINREVAIR. 
• Thrombocytopenia occurred more frequently in patients also receiving prostacyclin infusion (10.8% taking WINREVAIR and 0% taking placebo) compared with patients who were not taking prostacyclin infusion (3.1% of patients taking WINREVAIR and 3.1% of patients taking placebo). 

Telangiectasia

Events of telangiectasia were non-serious and did not progress in severity over time.

• In all patients exposed to WINREVAIR, the median time to onset was 47.1 weeks.
• Discontinuations of therapy due to telangiectasia were 1% in the WINREVAIR group vs 0% in the placebo group.
• No episodes of serious bleeding have been associated with telangiectasia. 

Increased blood pressure

Events of increased blood pressure (hypertension, blood pressure diastolic increased, blood pressure increased) were non-serious and no severe events were reported.

• In patients taking WINREVAIR, mean systolic blood pressure increased from baseline by 2.2 mmHg and diastolic blood pressure increased by 4.9 mmHg at 24 weeks.
• In patients taking placebo, the change from baseline in mean systolic blood pressure was -1.6 mmHg and -0.6 mmHg change in diastolic blood pressure.

Treatment discontinuation

The overall incidence of treatment discontinuations due to an adverse reaction was 4% in the WINREVAIR group and 7% in the placebo group.

There were no specific adverse reactions causing treatment discontinuations that occurred with a frequency greater than 1% and more often in the WINREVAIR group.

Long-term safety data

Long-term safety data are available from a Phase 2 clinical trial (PULSAR) that comprised a 24-week, double-blind, placebo-controlled treatment period followed by a 30-month, open-label extension period (n=104). A majority of these patients then continued into a long-term follow-up study.

• The mean duration of exposure to WINREVAIR in PULSAR and the long-term follow-up study was 151 weeks, with a maximum exposure of 218 weeks.
• The safety profile was generally similar to that observed in the pivotal STELLAR study.
• However, telangiectasia was not observed during the double-blind, placebo-controlled treatment period in PULSAR.
  • Telangiectasia was first reported in the open-label extension, occurring in 27% of patients at study completion, with a median time to onset of 106 weeks.

[SSI PLACEHOLDER]

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