Idorsia enrolls first patient into Precision phase 3 study of aprocitentan

Custom Synthesis,Idorsia has enrolled the first patient into its Phase 3 study called Precision to investigate the efficacy and safety of aprocitentan for resistant hypertension management in adults, defined as uncontrolled blood pressure.

In December 2017, Idorsia entered into a collaboration with Janssen Biotech, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson, to jointly develop and commercialize aprocitentan and any of its derivative compounds or products.

Prof. John Chalmers, Senior Director of The George Institute for Global Health and Professor of Medicine at the University of NSW Sydney, said that despite hypertension being a serious and growing problem around the world, there is surprisingly little research going on in the field. He said it has been over 30 years since an anti-hypertensive drug working via a new pathway has been brought to the market. Depending on the source of information, he said, it is estimated that anywhere from 5 to 30 per cent of the hypertension patient population can be classified as treatment ‘resistant’ due to their uncontrolled blood pressure levels despite receiving multiple antihypertensive medications, though ‘true resistant hypertension’ may be much less frequent, of the order of 5 to 10%. “There is an urgent public health need for additional therapies acting on pathways different from those currently used, in line with the underlying disease mechanism,” Chalmers said.

Martine Clozel, Chief Scientific Officer, said that the dose response of aprocitentan was consistent across blood pressure measurements, resulting in a minimum effective dose of 10 mg and an anticipated therapeutic dose of 25 mg. Clozel noted that aprocitentan was well tolerated across all doses. According to Clozel, the clinical pharmacology profile suggests that it has a low propensity for drug-drug interaction, and could therefore be combined with other background hypertension therapies as well as other medications. The CSO explained that this means that a compound targeting the endothelin pathway, one of the pathways in hypertension, could become a new treatment option for difficult to treat patients.

Guy Braunstein, Head of Global Clinical Development, said that the efficient study design of Precision has been established after consultation with regulatory agencies, including the FDA.

“The design will ensure that we are focused only on patients with true resistant hypertension. It intends also to minimize the placebo response in the treatment period. This maximizes the chance to demonstrate both the short-term blood pressure lowering effect of aprocitentan, when added to standard-of-care, and the durability of its effect on long-term resistant hypertension management,” Braunstein said.

He said that, if successful, the study should provide all the information required for filing and bring a therapy to patients who have exhausted many other options.