Insmed (INSM) Study result summary

Study design and patient population

• The open-label extension (OLE) study followed two phase II studies, enrolling 91 patients globally with PAH, including those who continued TPIP and those who crossed from placebo, allowing up-titration up to 1,280 mcg once daily.

• 95% of eligible patients from phase II enrolled in the OLE; 91% completed 12 months of treatment, with 83 patients completing the 12-month period.

• Baseline characteristics were balanced between groups, including age, sex, PAH subtype, and background medications.

• Physicians could titrate TPIP based on individual patient needs, mirroring real-world prostanoid use.

• The primary endpoint was long-term safety and tolerability; secondary endpoints included six-minute walk distance, NT-proBNP, WHO Functional Class, and REVEAL Lite 2.0 score.

Efficacy outcomes

• Sustained improvement in six-minute walk distance: +55.7 meters (continued TPIP) and +54.1 meters (placebo crossed) at 12 months.

• NT-proBNP reductions of ~60% from baseline were maintained through 12 months in both groups.

• Over 25% of patients achieved WHO Functional Class I by month 12; ~80% reached Class I or II.

• Mean REVEAL Lite 2.0 score improved by 2.0 points (continued TPIP) and 1.4 points (placebo crossed), with ~65% achieving refined low-risk status by month 12.

• Both patients continuing TPIP and those switching from placebo experienced similar positive outcomes across all efficacy measures.

Safety and tolerability

• TPIP was generally safe and well-tolerated, with no new safety signals at doses up to 1,280 mcg through 12 months.

• 89% experienced treatment-emergent adverse events, mostly mild or moderate; 18.7% had serious TEAEs; severe TEAEs in 16.5%.

• Most common TEAEs included headache, cough (mostly mild), dizziness, nasopharyngitis, diarrhea, and URTI.

• TEAEs led to discontinuation in 7.7% of patients; four deaths occurred, none related to TPIP.

• Mortality rate was 4% over 12 months, lower than the typical 8% for this population.