China Approves Johnson & Johnson’s Macitentan Tablets After Trial Involving 148 Patients
Key Facts
A report published on November 5 said China’s National Medical Products Administration had approved Johnson & Johnson’s dispersible macitentan tablets. Citing the agency’s website, the report said the likely indication was pulmonary arterial hypertension in children. The decision makes the drug one of the options available to this patient group in China. But describing the indication as likely reflects the report’s wording on the treatment’s purpose; the report provided no further details on the approval conditions or the approved age group in China. The news is notable alongside data from a clinical trial of macitentan in children and adolescents with the disease.
The multicenter, open-label TOMORROW trial enrolled participants aged 2 to under 18 years. It included patients in World Health Organization functional classes I to III. The trial was designed to compare macitentan with standard of care, with the drug’s dose determined by the patient’s weight. Participants were randomly assigned in a 1:1 ratio to the two groups, while standard of care could include up to two pulmonary arterial hypertension-specific treatments. This design shows the range of patients and comparator treatment covered by the trial, but does not by itself mean its results conclusively establish the drug’s efficacy.
A total of 148 participants were randomized, including 73 in the macitentan group and 75 in the standard-of-care group. The similar group sizes show how the study sample was allocated between the two treatments. The report cited a statistically significant improvement in children’s quality-of-life assessments at week 24 compared with standard of care, with a p-value of 0.043. Parent reports also showed a statistically significant improvement, with a p-value of 0.020. The two results covered assessments by children and their families, separate measures highlighted in the report’s trial data.
The trial record has an important clinical limitation in the U.S. regulatory assessment. The U.S. Food and Drug Administration said the company had not sought approval for macitentan to treat pulmonary arterial hypertension in children because the Phase 3 study did not establish efficacy or safety in this group. The agency added that the company changed the study’s primary endpoint to pharmacokinetics because of difficulties recruiting participants. This provides necessary context for interpreting the TOMORROW results, including the quality-of-life improvements, as the U.S. review did not consider them evidence establishing efficacy and safety. That assessment pertains to the U.S. agency’s review, while the report cited approval by China’s agency and described the pediatric indication as likely.
In an analysis published in the Journal of Pediatrics, the NT-proBNP ratio to baseline was 72% in the macitentan group at week 12, compared with 101% in the standard-of-care group. The difference between the groups was not statistically significant, with a p-value of 0.086. This result adds another measure to the trial data, but does not provide conclusive statistical evidence that macitentan was superior on this measure. The results therefore vary by measure: statistically significant improvement in quality-of-life assessments, versus a difference that was not statistically significant in the NT-proBNP ratio. This distinction remains relevant when placing the regulatory approval news in the context of the clinical evidence available in the report.
In the market, Johnson & Johnson shares closed at $272.32 on November 5, compared with a close of $276.32 in the previous session. This places the share move on the day the approval news was published in its daily context, without establishing that the news caused the change between the two closes. In China, the drug news came as activity indicators pointed to continued expansion at a slower pace. The composite production index, which combines manufacturing and services, fell to 52.0 points in October from 52.4 points in September. October’s reading marked the index’s slowest expansion in three months, according to Investing.com.