Johnson & Johnson’s $230 million blood pressure bet has hit the mark in phase 3. The Idorsia-partnered prospect significantly reduced blood pressure in patients with resistant hypertension, although the rate of fluid retention and initial lack of detail on efficacy leave scope to question whether it will live up to its blockbuster billing.
J&J opted into the development of the dual endothelin receptor antagonist aprocitentan in 2017, paying $230 million upfront and agreeing to a royalty rate that runs from 20% to 35% to secure global rights to aprocitentan. The deal came months after the delivery of phase 2 data from Idorsia, which was created earlier in 2017 as part of J&J’s $30 billion takeover of Actelion. Earlier this year, analysts at Jefferies tipped aprocitentan to achieve peak sales of $2.5 billion given the “vast market opportunity.”
The phase 3 results will shape whether aprocitentan can capture that blockbuster opportunity. The multipart clinical trial began with a four-week treatment period that included 730 patients who consistently had systolic blood pressure of 140 mmHg or more despite receiving the recommended antihypertensive therapy during the screening stage of the study.
After four weeks of treatment with placebo or one of two doses of aprocitentan, Idorsia saw statistically significant improvements in systolic blood pressure in both treatment arms. The improvements caused both the 12.5-mg and 25-mg cohorts to hit the primary endpoint with p-values of less than 0.005. Investors responded positively to the data, sending shares in Idorsia up around 6% to above 16 Swiss francs ($16) in early trading in Switzerland.
In the second part of the study, all participants received 25 mg of aprocitentan for 32 weeks. Idorsia said the blood pressure reductions were maintained, and subjects who switched from placebo experienced the same blood pressure reduction as seen in the first part of the trial.
The third part of the study re-randomized 614 patients to receive 25 mg of aprocitentan or placebo for 12 weeks. After four weeks, the blood pressure in the placebo arm increased significantly compared to the treatment group, causing the study to hit that secondary endpoint with a p-value of less than 0.0001.
On the safety front, fluid retention was a particular focus given the effects of other endothelin receptor antagonists. Idorsia saw four cases of peripheral edema, a form of fluid retention, in the 327 people who received aprocitentan in phase 2, putting the rate of the adverse event at around 1%.
In the phase 3 clinical trial, approximately 30% of patients developed edema or fluid retention at one time point during the entire study. More than 95% of the cases were mild or moderate. Two cases, both in the 25-mg cohort, were serious, and seven patients dropped out because of the side effect. Most cases happened in the initial four-week treatment period, when 9.1% of patients on the low dose and 18.4% of people on the high dose suffered the adverse event. The rate in the placebo arm was 2.1%.