SUMMARY

• The phase 2 MUSIC trial was conducted to assess the safety and efficacy of OPSUMIT in adult patients with idiopathic pulmonary fibrosis (IPF) of <3 years duration.¹
• This study did not meet its primary endpoint of improvement in forced vital capacity (FVC) vs placebo at month 12. No differences were observed in pulmonary function tests or time to disease worsening or death.¹
• The percentage of patients with serious adverse events (AEs) was similar across groups. Compared to placebo, a higher percentage of OPSUMIT-treated patients had dyspnea, peripheral edema, and anemia.¹
• The incidence of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) elevations >3 × upper limit of normal (ULN) were similar between the OPSUMIT and placebo groups.¹

CLINICAL DATA

Clinical Experience in IPF

The Macitentan USe in an Idiopathic pulmonary fibrosis Clinical (MUSIC) trial was a prospective, randomized, double-blind, multicenter, parallel-group, placebo-controlled phase 2 proof of concept trial.¹ This study included 178 patients diagnosed with IPF according to the American Thoracic Society (ATS)/ European Respiratory Society (ERS) consensus conference criteria with surgical lung biopsy (SLB).² Adult patients with IPF of <3 years duration and a histological pattern of usual interstitial pneumonia (UIP) on surgical lung biopsy were randomized 2:1 to receive OPSUMIT (n=119) or placebo (n=59) once daily. Patients with interstitial lung disease were excluded if they had lung disease due to conditions other than IPF; FVC <50% of predicted values or <1.2 L; diffusing capacity for carbon monoxide corrected for hemoglobin (DL_CO) <30% of predicted values; residual volume ≥120% of predicted values; obstructive lung disease (defined as forced expiratory volume in 1 second [FEV₁]/FVC <0.70).¹

The primary endpoint was change in FVC compared to placebo.¹ Secondary endpoints include time to disease worsening or death, and safety.

The primary endpoint of the MUSIC study was not met.¹ In all randomized patients, the median change from baseline up to Month 12 in FVC was −0.20 L (−2.86 to 0.42) in the OPSUMIT arm and −0.20 L (−4.12 to 0.62) in the placebo arm. Please see Table: Pulmonary Function Test Results below for pulmonary function test study results.¹

The safety set comprised 178 patients who received at ≥1 dose of study treatment.¹ Exposure to study treatment was similar in each group, with an average duration of 14.5 months in the OPSUMIT group and 15.0 months in the placebo group.

AEs occurring in ≥10% of OPSUMIT-treated patients are shown in Table: AEs Occurring in ≥10% of OPSUMIT-Treated Patients below.¹ A total of 15 OPSUMIT-treated patients (12.6%) and 7 placebo recipients (11.9%) experienced AEs that led to premature discontinuation of study treatment. A total of 37 OPSUMIT-treated patients (31.1%) and 20 placebo recipients (33.9%) experienced ≥1 serious AE. Please refer to Table: Serious AEs Occurring in >1 OPSUMIT-Treated Patients below for serious AEs occurring in >1
OPSUMIT-treated patients. In total, 3.4% of OPSUMIT-treated patients and 5.1% of placebo recipients exhibited AST and/or ALT elevations >3 × ULN. Thirteen patients died during treatment or up to 28 days after discontinuation of study drug; 9 patients (7.6%) in the OPSUMIT arm and 4 (6.8%) in the placebo arm. The most common causes of death were IPF worsening (OPSUMIT, n=2 [1.7%]; placebo, n=4 [6.8%]) and respiratory failure (OPSUMIT, n=3 [2.5%]; placebo, n=1 [1.7%]).¹

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 21 January 2025.