GRIPHON Subgroup Analyses:
Triple Combination

Griphon subgroup analyses triple combination selector

For context, GRIPHON overall population information is shown below. Select an icon or scroll for FC II and FC III triple-combination subgroup data.

Overall
Population
Triple
Combination
FC II
Triple Combo
FC III
Triple Combo

GRIPHON Phase 3 Study1:

  • Long-term, multicenter, double-blind, placebo-controlled, parallel-group, event-driven study
  • Enrolled 1156 patients with PAH
    • UPTRAVI: n=574, placebo: n=582
    • >98% WHO FC II-III at baseline
  • Median duration of exposure to UPTRAVI: 1.4 years
    • Maximum: 4.2 years
Overall
Population
Triple
Combination
FC II
Triple Combo
FC III
Triple Combo

Subgroup Analysis:
GRIPHON—The ONLY PAH Outcomes Trial That Included Patients Treated With TRIPLE-combination Therapy1-3*

Patients receiving ERA and PDE-5i at baseline were a prespecified subgroup for evaluation of the GRIPHON primary endpoint; however, the more detailed analyses described here are exploratory and post hoc. Sample size should be considered and results should be interpreted with caution.

Baseline patient characteristics and notable differences from overall population

  • 33% (n=376) of all patients in GRIPHON were on ERA and PDE-5i background therapy at baseline
  • The triple-combination subgroup had a longer time from diagnosis (3.8 years vs 2.4 years in the overall population), a larger percentage from Western Europe/Australia (52.9% vs 27.8%), and a larger percentage from North America (28.5% vs 16.7%)

POST HOC ANALYSIS: 
37% RISK REDUCTION OF DISEASE PROGRESSION IN PATIENTS ALREADY RECEIVING ERA + PDE-5i

The treatment effect on time to first event in patients receiving ERA + PDE-5i was consistent with the overall population.

Tolerability was generally consistent with the 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. See the Important Safety Information below for the most frequent adverse reactions in the overall population. Adverse reactions in the triple-combination subgroup notably different from the overall population§ (UPTRAVI n=179 vs placebo n=197): headache (76.0% vs 38.6%), diarrhea (55.9% vs 26.4%), nausea (47.5% vs 24.9%), jaw pain (41.3% vs 10.2%), vomiting (23.5% vs 10.7%), pain in extremity (22.9% vs 10.2%), and flushing (20.1% vs 8.1%).

Overall
Population
Triple
Combination
FC II
Triple Combo
FC III
Triple Combo

Subpopulation Analysis:
GRIPHON—The ONLY PAH Outcomes Trial That Included FC II Patients Treated With TRIPLE-combination Therapy1-3*

ERA + PDE-5i +/- UPTRAVI in FC II

This subgroup analysis was post hoc and exploratory. Sample size should be considered and results should be interpreted with caution.

Baseline patient characteristics and notable differences from overall population

  • 10% (n=115) of all patients in GRIPHON were FC II on ERA and PDE-5i background therapy at baseline
  • The FC II triple-combination subpopulation had a longer time from diagnosis (4 years vs 2.4 years in the overall population), a larger percentage from Western Europe/Australia (43.5% vs 27.8%), and a larger percentage from North America (31.3% vs 16.7%)

POST HOC ANALYSIS: 
RISK REDUCTION OF DISEASE PROGRESSION IN FC II PATIENTS ALREADY RECEIVING ERA + PDE-5i

Reductions in PAH-related hospitalization and other disease progression events drove the overall risk reduction.

Tolerability was generally consistent with the overall population. Similar to the overall population, treatment-related adverse reactions were more frequent during titration. See the Important Safety Information below for the most frequent adverse reactions in the overall population. Adverse reactions in the FC II triple-combination subpopulation notably different from the overall population (UPTRAVI n=55 vs placebo n=60): headache (78.2% vs 30.0%), diarrhea (58.2% vs 13.3%), nausea (54.5% vs 20.0%), jaw pain (38.2% vs 5.0%), fatigue (14.5% vs 10.0%), bronchitis (12.7% vs 8.3%), abdominal pain (14.5% vs 8.3%), and decreased appetite (10.9% vs 5.0%).

Overall
Population
Triple
Combination
FC II
Triple Combo

Subpopulation Analysis:
GRIPHON—The ONLY PAH Outcomes Trial That Included FC III Patients Treated With TRIPLE-combination Therapy1-3*

ERA + PDE-5i +/- UPTRAVI in FC III

This subgroup analysis was exploratory and post hoc. Sample size should be considered and results should be interpreted with caution.

Baseline patient characteristics and notable differences from overall population

  • 22% (n=255) of all patients in GRIPHON were FC III on ERA and PDE-5i background therapy at baseline
  • The FC III triple-combination subpopulation had a longer time from diagnosis (3.8 years vs 2.4 years in the overall population), a larger percentage from Western Europe/Australia (56.9% vs 27.8%), a larger percentage from North America (27.5% vs 16.7%), and an older average age (52 years vs 48.1)

POST HOC ANALYSIS: 
RISK REDUCTION OF DISEASE PROGRESSION IN FC III PATIENTS ALREADY RECEIVING ERA + PDE-5i

Reductions in PAH-related hospitalization and other disease progression events drove the overall risk reduction.

Tolerability was generally consistent with the overall population. Similar to the overall population, treatment-related adverse reactions were more frequent during titration. See the Important Safety Information below for the most frequent adverse reactions in the overall population. Adverse reactions in the FC III triple-combination subpopulation notably different from the overall population (UPTRAVI n=122 vs placebo n=133): jaw pain (42.6% vs 12.0%), vomiting (23.0% vs 9.8%), pain in extremity (26.2% vs 12.0%), and flushing (21.3% vs 8.3%).