The Zhitong Finance App learned that on November 5, the official website of the National Drug Administration (NMPA) showed that Johnson & Johnson (JNJ.US) mazitentan dispersible tablets were approved for marketing. The presumed indication is pulmonary hypertension in children.
TOMORROW is a multi-center, open-label phase III clinical trial involving patients aged ≥2 to <18 years of age, World Health Organization (WHO) grade I-III cardiac function. Patients were randomly assigned 1:1 to the macetentam group (administration by body weight) or SoC group (≤ 2 PAH-specific treatments). The primary endpoint was steady state valley concentration (Ctrough) plasma level of macetentan and its active metabolite aprocitentan at week 12. Secondary endpoints include time to the first clinical worsening event (disease progression as confirmed by the Incident Decision Committee), safety/tolerability, changes in NT-proBNP, and quality of life.
A total of 148 patients were randomized (n = 73 in the macitentam group; n = 75 in the SoC group). The PK characteristics were consistent with the adult population; the mean values (standard deviations) of steady-state valley concentrations were: macetentan 185 (114.3) ng/mL, aprocitentan 983 (324.1) ng/mL, respectively. Average treatment time: 183.36 weeks in the macitentam group and 130.59 weeks in the SoC group. Risk ratio to event analysis (95% CI, macitentane vs. SoC): disease progression was 0.828 (0.460—1.492), PAH hospitalization was 0.912 (0.393-2.118), PAH death was 1.530 (0.429—5.457) (all P>.05). NT-proBNP as a percentage of baseline: 72% in the macitentam group vs. 101% in the SoC group at week 12 (P=.086), 76% vs. 78% (P=.884) at week 24.
Quality of life assessments showed clinically significant improvements in children (week 24, P = .043) and parents (P = .020) compared to SoC. The safety of macitentan is consistent with what has been seen in the adult population.