Deep in talks with J&J, Actelion’s flagship drug cruises past a pivotal trial failure

Professor Nazzareno Galiè, University of Bologna

Deep into negotiations with J&J over a prospective buyout, Actelion (SIX: ATLN) reported today that its up-and-coming flagship therapy Opsumit flunked a pivotal test for treating pulmonary arterial hypertension due to Eisenmenger Syndrome. And while the trial failure could put a crimp in Actelion’s — as well as J&J’s — plan to continue to rapidly boost sales of Opsumit as Tracleer loses ground to generic competition, analysts seemed ready to write it off and move on.

Investigators for the Swiss biotech say they tracked the kind of biomarker impact they were looking for, but Opsumit (macitentan) did not improve patients’ six-minute walk tests when compared to a placebo. And they added that it was likely an unusual placebo response that caused the unexpected setback.

In fact, the drug arm actually performed worse than the placebo group.  Placebo patients gained an average of 19.7 meters from baseline compared to an inferior 18.3 meter gain in the Opsumit arm. If you wash out three patients with missing 6-minute results, the improvement in the drug arm goes up to 30.2 meters.

Opsumit is already approved to treat PAH. But Actelion execs felt they had a good shot at boosting their market reach by going after the sickest patient population in PAH. These patients suffer from advanced PAH along with congenital heart disease. And the population includes a large number of people suffering from Down Syndrome.

Jefferies’ Peter Welford, who estimates peak sales at $2.3 billion, shrugged off the failure. He noted:

We did not specifically ascribe sales or an NPV to Opsumit for this indication but believe the adverse impact is relatively minor. Estimates suggest up to 15k Eisenmenger patients WW, <5% of the PAH population. Tracleer is approved in Europe to treat PAH due to Eisenmenger after demonstrating a significant +53m benefit on the 6-minute walk distance (6MWD).

Welford also doubts that J&J will be seriously put off by the study results. The pharma giant has been quietly engaged in exclusive talks with Actelion after initially walking away from negotiations.

Investors apparently agreed with that assessment. Actelion’s shares moved up this morning in anticipation of a deal with J&J.

Professor Nazzareno Galiè, head of the Pulmonary Hypertension Center at the Institute of Cardiology, University of Bologna and steering committee member for the MAESTRO study, commented:

The results of the MAESTRO study are very difficult to interpret. We have seen encouraging positive effects of macitentan in the response of N-terminal pro b-type natriuretic peptide plasma levels and hemodynamic measures. Although the results point towards a benefit of treatment with macitentan, we do not see a significant treatment effect on the primary endpoint of exercise capacity as measured in the 6 minute walk test. I believe this has been influenced by an unexpected improvement in the placebo arm of the study, which is unusual in a predominantly untreated PAH population. In fact, we have not seen such a persistent placebo effect in the multiple studies published so far in PAH. We need to fully analyze the data to understand what could have caused this phenomenon.

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