Actelion has revealed that a late-stage trial of Opsumit in patients with Eisenmenger syndrome failed to meet its objectives, just as it is immersed in takeover talks with Johnson & Johnson (J&J).
The results of the MAESTRO trial showed that after 16 weeks’ treatment, endothelin antagonist Opsumit (macitentan) was unable to achieve an improvement in the six-minute walk test – the primary outcome measure – compared to placebo.
MAESTRO involved 266 patients with pulmonary artery hypertension (PAH) caused by Eisenmenger syndrome, an umbrella term for congenital cardiac defects that lead to left-to-right shunts – reversal of blood flow from the right side of the circulation to the left – which increase pulmonary blood flow.
After 16 weeks, patients on Opsumit were able to walk an extra 18.3 metres in the walk-test, but that compared to a 19.7-metre increase in the placebo group. Secondary endpoints suggested a benefit for the active drug, including a reduction in vascular resistance and biomarkers such as N-terminal pro b-type natriuretic peptide.
Analysts at Deutsche Bank said the trial failure was unlikely to lead to a breakdown in talks between Switzerland-based Actelion and J&J, and was a ‘modest disappointment’ that would affect the Swiss biopharma company’s efforts to differentiate Opsumit from competitors.
Overall, it could reduce Opsumit’s sales potential by around CHF 200m ($200m) a year, they suggested. Opsumit sales were CHF 586m in the first nine months of 2016, up two-thirds on the same period of 2015 and closing the gap on Actelion’s older endothelin antagonist Tracleer (bosentan) which has lost patent protection in the US and Europe.
Actelion also has a third PAH drug – Uptravi (selexipag) – that has grown quickly since its launch and is predicted to hit $1bn in sales by 2020.
Actelion started negotiating with J&J about a possible takeover last November, only to reject the US firm’s overtures in favour of a possible deal with France’s Sanofi. Mere days later, talks with Sanofi had broken down and the Swiss firm was back at the table with J&J before the Christmas holidays. Since then there has been no update from either company on progress towards a deal.
Discussing the results of the MAESTRO trial, investigator Nazzareno Galiè of the University of Bologna, said the data was “difficult to interpret” and probably “influenced by an unexpected improvement in the placebo arm of the study, which is unusual in a predominantly untreated PAH population”.
“We need to fully analyse the data to understand what could have caused this phenomenon,” he added.