Idorsia first-in-class hypertension drug gets FDA okay

Idorsia Pharmaceuticals has claimed FDA approval for aprocitentan as a treatment for resistant hypertension, becoming the first drug in the endothelin receptor antagonist class for that indication.

The approval comes just a few months after Johnson & Johnson’s Janssen Biotech unit handed back rights to the drug in resistant hypertension, although the two companies are still partnered on a follow-up use in pulmonary hypertension. As part of the exit, Idorsia could pay J&J around $340 million to re-acquire rights, with the total amount dependent on regulatory and commercial milestones.

Aprocitentan will be sold under the Tryvio brand name in the US and will be an add-on option for patients who can’t control their blood pressure using other therapies. It represents the first new therapeutic pathway to be approved for high blood pressure in almost 40 years.

In the phase 3 PRECISION trial, aprocitentan met its main objective of reducing systemic blood pressure compared to placebo, with an overall reduction of 3.8 mmHg with a daily oral dose of 12.5 mg aprocitentan at four weeks.

It is thought that around 10% of the 1.3 billion people with hypertension around the world struggle to control their blood pressure using the current main classes of antihypertensive, namely diuretics, calcium channel blockers, and renin-angiotensin system-targeting drugs.

J&J’s decision to exit the resistant hypertension partnership last September raised eyebrows, particularly so late in the FDA review process, but came after a three-month delay caused by a request for more materials from Idorsia to support a risk evaluation and mitigation strategy (REMS) for the drug.

Tryvio has been approved with a black box warning for major birth defects if the drug is used during pregnancy.

Idorsia said it intends to launch Tryvio in the second half of the year, fuelling speculation that it may be on the hunt for a new commercial partner for the drug. There’s no news yet on its pricing plans.

The Swiss company is still somewhat in recovery mode after the unexpected failure last year of clazosentan in the REACT trial, which was testing the drug as a treatment for a brain injury known as aneurysmal subarachnoid haemorrhage.

Idorsia's chief executive, Jean-Paul Clozel, said that uncontrolled hypertension is a major public health issue, raising the risk of cardio- and cerebrovascular events.

“Idorsia conducted an ambitious clinical programme in patients remaining hypertensive despite a minimum of three drugs at their optimal dose and sometimes up to four, five, or even six antihypertensives,” he added. “I’m very proud of the Idorsia team and very happy that physicians will have a new treatment option to treat patients whose blood pressure is not controlled.”

When Idorsia filed aprocitentan with the US regulator in December 2022, analysts at Jefferies predicted that it had the potential to become a $2.5 billion blockbuster, due to the urgent need for new therapies for people with uncontrolled hypertension.

GlobalData is less optimistic, modelling sales of $141 million for the drug out of a total treatment-resistant hypertension market of $895 million across several of the larger pharma markets in 2030. The market analytics company predicted in a recently published report that Tryvio will trail AstraZeneca’s aldosterone synthase inhibitor baxdrostat, currently in phase 3, which it reckons could bring in more than $500 million in the same year.