Science and Research

Long-Term Safety and Efficacy of Macitentan in Inoperable Chronic Thromboembolic Pulmonary Hypertension: Results from MERIT and its Open-Label Extension

INTRODUCTION: Evidence for use of pulmonary arterial hypertension targeted-therapies in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is limited. In MERIT-1, the endothelin receptor antagonist macitentan improved hemodynamic and functional parameters versus placebo in patients with inoperable CTEPH over a 24-week double-blind (DB) period. Its open-label (OL) extension study (MERIT-2) provides long-term safety/efficacy data. METHODS: MERIT-2 (NCT02060721) was a multicenter, single-arm, OL, phase 2 extension study of MERIT-1. Patients completing MERIT-1 were eligible to receive 10 mg macitentan once-daily in MERIT-2. Safety and efficacy (6-min walk distance [6MWD] and change in World Health Organization functional class [WHO FC]) were assessed in all patients in MERIT-2 regardless of treatment received in DB (All patients MERIT-2 OL macitentan 10 mg group) and the subgroup of patients receiving DB macitentan in MERIT-1 (Long-term [DB/OL] macitentan 10 mg subgroup). RESULTS: Of the 80 patients randomized in MERIT-1, 76 entered MERIT-2 (All patients MERIT-2 OL macitentan 10 mg group): 40 who received DB macitentan (DB-macitentan patients) and 36 DB placebo (DB-placebo patients). Median (interquartile range) macitentan exposure in the All patients MERIT-2 OL macitentan 10 mg group was 45.5 (26.0, 66.1) months. During the OL period, treatment-emergent adverse events (AE) were reported in 72 (94.7%) patients; most frequent were worsening of pulmonary hypertension (19.7%), decreased hemoglobin (18.4%) and upper respiratory tract infection (15.8%). Fourteen (18.4%) patients died; none were assessed as macitentan-related. At Month 6 post-OL baseline, mean (standard deviation) change in 6MWD was - 0.4 m (43.62) for DB-macitentan patients and 10.7 m (45.63) for DB-placebo patients; the majority had unchanged (83.3%) or improved (12.5%) WHO FC. Safety/efficacy analyses were consistent in the Long-term (DB/OL) macitentan 10 mg subgroup. CONCLUSION: These analyses provide long-term safety/efficacy data in patients with inoperable CTEPH treated with macitentan. No unexpected safety findings occurred; reported AEs were consistent with the known safety profile of macitentan. At 6 months post-OL baseline, DB-placebo patients modestly improved 6MWD; DB-macitentan patients maintained improvements observed in MERIT-1. WHO FC was largely unchanged. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT02021292; NCT02060721.

  • Kim, N. H.
  • D'Armini, A. M.
  • Howard, L. S.
  • Jenkins, D. P.
  • Jing, Z. C.
  • Mayer, E.
  • Chamitava, L.
  • Lack, G.
  • Rofael, H.
  • Solonets, M.
  • Ghofrani, H. A.

Keywords

  • Chronic thromboembolic pulmonary hypertension
  • Inoperable
  • Macitentan
  • Open-label
  • Phase 2
Publication details
DOI: 10.1007/s41030-024-00276-w
Journal: Pulm Ther
Work Type: Original
Location: UGMLC
Disease Area: PH
Partner / Member: JLU
Access-Number: 39520648

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