GRIPHON Trial for PAH, Subgroup Analysis | UPTRAVI® (selexipag)

post hoc analysis: triple-combination subgroup GRIPHON—The FIRST and ONLY COMPLETED PAH Outcomes Trial That Included Patients Treated With TRIPLE-Combination Therapy^1-3

The information below is from a post hoc subgroup analysis of the GRIPHON trial.
View the GRIPHON pivotal data for context of the overall population.

Triple Combination

Post Hoc SUBGROUP Analysis: 37% Risk Reduction of Disease Progression in Patients TREATED WITH UPTRAVI + ERA + PDE-5i^1-3

Baseline patient characteristics

33% (n=376) of all patients in GRIPHON were receiving an ERA and a PDE-5i at baseline (31% FC II and 68% FC III)*
Etiology in triple-combination subgroup: IPAH/HPAH (64%), PAH-CTD (26%), PAH-CHD (5%), other (5%)

Notable differences from overall population

The triple-combination subgroup had:

Longer time from diagnosis (3.8 years vs 2.4 years in the overall population)
Larger percentage from Western Europe/Australia (52.9% vs 27.8%)
Larger percentage from North America (28.5% vs 16.7%)

Time to first disease progression event

Time to first disease progression event

Time to first disease progression event

The treatment effect was established early and maintained over the entire treatment period

Events in patients receiving ERA + PDE-5i at baseline

Adverse reactions in triple-combination subgroup notably different from overall population^‡

Tolerability was generally consistent with overall population
The most common adverse reactions were headache, diarrhea, nausea, and jaw pain
Similar to the overall population, treatment-related adverse reactions were more frequent during titration

FC II Triple Combination

Post Hoc Subpopulation Analysis: 64% Risk Reduction of Disease Progression in FC II Patients already receiving ERA + PDE-5i^1-3

Baseline patient characteristics

10% (n=115) of all patients in GRIPHON were FC II and receiving an ERA and a PDE-5i at baseline
Etiology in FC II triple-combination subpopulation: IPAH/HPAH (70%), PAH-CTD (18%), PAH-CHD (6%), other (6%)

Notable differences from overall population

The FC II triple-combination subpopulation had:

Longer time from diagnosis (4 years vs 2.4 years in the overall population)
Larger percentage from Western Europe/Australia (43.5% vs 27.8%)
Larger percentage from North America (31.3% vs 16.7%)

Time to first disease progression event in FC II patients
receiving ERA + PDE-5i at baseline

Time to first disease progression event in FC II patients receiving ERA + PDE-5i at baseline

Time to first disease progression event in FC II patients receiving ERA + PDE-5i at baseline

Events in FC II patients receiving ERA + PDE-5i at baseline

Adverse reactions in FC II triple-combination subpopulation notably different from overall population^§

Tolerability was generally consistent with overall population
Similar to the overall population, treatment-related adverse reactions were more frequent during titration

FC III Triple Combination

Post Hoc Subpopulation Analysis: 26% Risk Reduction of Disease Progression in FC III Patients already receiving ERA + PDE-5i^1-3

Baseline patient characteristics

22% (n=255) of all patients in GRIPHON were FC III and receiving an ERA and a PDE-5i at baseline
Etiology in FC III triple-combination subpopulation: IPAH/HPAH (61%), PAH-CTD (29%), PAH-CHD (5%), other (4%)

Notable differences from overall population

The FC III triple-combination subpopulation had:

Longer time from diagnosis (3.8 years vs 2.4 years in the overall population)
Larger percentage from Western Europe/Australia (56.9% vs 27.8%)
Larger percentage from North America (27.5% vs 16.7%)
Older average age (52 years vs 48.1 years)

Time to first disease progression event in FC III patients
receiving ERA + PDE-5i at baseline

Time to first disease progression event in FC III patients receiving ERA + PDE-5i at baseline

Time to first disease progression event in FC III patients receiving ERA + PDE-5i at baseline

Events in FC III patients receiving ERA + PDE-5i at baseline

Adverse reactions in FC III triple-combination subpopulation notably different from overall population^‖

Tolerability was generally consistent with overall population
Similar to the overall population, treatment-related adverse reactions were more frequent during titration

Learn about the proven
efficacy of UPTRAVI

View the GRIPHON Results

UPTRAVI time-from-
diagnosis subgroup analyses

UPTRAVI PAH-CTD
subgroup analysis

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Concomitant use of strong inhibitors of CYP2C8 (eg, gemfibrozil) with UPTRAVI is contraindicated.

WARNINGS AND PRECAUTIONS

Pulmonary Veno-Occlusive Disease (PVOD)

Should signs of pulmonary edema occur, consider the possibility of associated PVOD. If confirmed, discontinue UPTRAVI.

ADVERSE REACTIONS

Adverse reactions more frequent compared to placebo (≥3%) are headache (65% vs 32%), diarrhea (42% vs 18%), jaw pain (26% vs 6%), nausea (33% vs 18%), myalgia (16% vs 6%), vomiting (18% vs 9%), pain in extremity (17% vs 8%), flushing (12% vs 5%), arthralgia (11% vs 8%), anemia (8% vs 5%), decreased appetite (6% vs 3%), and rash (11% vs 8%).

These adverse reactions are more frequent during the dose titration phase.

Hyperthyroidism was observed in 1% (n=8) of patients on UPTRAVI and in none of the patients on placebo.

DRUG INTERACTIONS

CYP2C8 Inhibitors

Concomitant administration with gemfibrozil, a strong inhibitor of CYP2C8, doubled exposure to selexipag and increased exposure to the active metabolite by approximately 11-fold. Concomitant use of UPTRAVI with strong inhibitors of CYP2C8 is contraindicated.

Concomitant administration of UPTRAVI with clopidogrel, a moderate inhibitor of CYP2C8, had no relevant effect on the exposure to selexipag and increased the exposure to the active metabolite by approximately 2.7–fold. Reduce the dosing of UPTRAVI to once daily in patients on a moderate CYP2C8 inhibitor.

CYP2C8 Inducers

Concomitant administration with an inducer of CYP2C8 and UGT 1A3 and 2B7 enzymes (rifampin) halved exposure to the active metabolite. Increase UPTRAVI dose, up to twice, when co-administered with rifampin. Reduce UPTRAVI when rifampin is stopped.

DOSAGE AND ADMINISTRATION

Recommended Dosage

Recommended starting dose is 200 mcg twice daily. Tolerability may be improved when taken with food. Increase by 200 mcg twice daily, usually at weekly intervals, to the highest tolerated dose up to 1600 mcg twice daily. If dose is not tolerated, reduce to the previous tolerated dose.

Patients With Hepatic Impairment

For patients with moderate hepatic impairment (Child-Pugh class B), the starting dose is 200 mcg once daily. Increase by 200 mcg once daily at weekly intervals, as tolerated. Avoid use of UPTRAVI in patients with severe hepatic impairment (Child-Pugh class C).

Co-administration With Moderate CYP2C8 Inhibitors

When co-administered with moderate CYP2C8 inhibitors (eg, clopidogrel, deferasirox and teriflunomide), reduce the dosing of UPTRAVI to once daily. Revert back to twice daily dosing frequency of UPTRAVI when co-administration of moderate CYP2C8 inhibitor is stopped.

Dosage Strengths

UPTRAVI tablet strengths:
200, 400, 600, 800, 1000, 1200, 1400, and 1600 mcg.

Please see full Prescribing Information.

INDICATION

UPTRAVI® (selexipag) is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH.

Effectiveness was established in a long-term study in PAH patients with WHO Functional Class II-III symptoms.

Patients had idiopathic and heritable PAH (58%), PAH associated with connective tissue disease (29%), and PAH associated with congenital heart disease with repaired shunts (10%).