Actelion's Opsumit fails in late-stage study of PAH due to Eisenmenger syndrome

Actelion reported Monday that a late-stage study of Opsumit (macitentan) in patients with pulmonary arterial hypertension (PAH) due to Eisenmenger syndrome failed to meet its primary objective. The company noted that in the MAESTRO trial, after 16 weeks of treatment, the mean change in 6-minute walk distance from baseline was an increase of 18.3 metres in the Opsumit group and 19.7 metres in the placebo group.

In the study, 226 patients with PAH due to Eisenmenger syndrome were randomised to once-daily treatment with Opsumit or placebo for 16 weeks. The drugmaker explained that the 6-minute walk distance least-squares mean difference between the groups at week 16 was -4.7 metres. Meanwhile, Actelion indicated that in the per-protocol population, the mean change in the 6-minute walk distance from baseline was 30.2 metres in the Opsumit group, versus 18.9 metres for placebo. Additionally, the 6-minute walk distance least-squares mean difference between the Opsumit and placebo arms was 6.4 metres. 

Additionally, Actelion observed a 20-percent reduction in the exploratory biomarker endpoint N-terminal pro b-type natriuretic peptide after 16 weeks in the Opsumit arm versus placebo in the entire study population, while in a sub-study of 39 patients, the pulmonary vascular resistance index was reduced by 13 percent in the Opsumit arm compared to placebo. The company said it plans to conduct a full analysis of the study and submit the data for publication in a peer-reviewed journal.

Commenting on the findings, Nazzareno Galiè, steering committee member for the MAESTRO study, said "the results...are very difficult to interpret," adding "although the results point towards a benefit of treatment with [Opsumit], we do not see a significant treatment effect on the primary endpoint of exercise capacity as measured in the 6 minute walk test." Galiè suggested that the findings may have been influenced by an "unexpected improvement" in the placebo arm of the study.

Opsumit was approved by the FDA for the treatment of PAH in adults in October in 2013. The oral endothelin receptor antagonist was cleared in Europe for the same indication later that year. Opsumit generated sales of 218 million francs ($218 million) in the third quarter of 2016.

Analysts suggested that the results of the MAESTRO study weaken Opsumit's revenue potential by as much as 200 million Swiss francs ($200 million) per year, although they said this was unlikely to impact Johnson & Johnson's interest in a deal with Actelion. "The failure is a modest disappointment to the company's efforts to differentiate Opsumit and protect it from price pressure," remarked Deutsche Bank analyst Richard Parkes, with analysts at Jefferies calling the adverse impact "likely minor." 

Earlier this month, Johnson & Johnson reportedly reached a tentative agreement regarding price for a proposed takeover of Actelion. The drugmakers entered into exclusive negotiations last month after previously terminating talks due to disagreements about the structure of a deal (for related analysis, see ViewPoints: Clozel's mind-set says much about Johnson & Johnson's Actelion pursuit.