J&J, Idorsia plan filings for aprocitentan data in resistant hypertension

People whose blood pressure remains stubbornly high despite current drug treatment and are at increased risk of complications such as kidney disease and stroke could have another treatment option in future, developed by Johnson & Johnson and Idorsia. The two partners have reported the first phase 3 results with dual endothelin receptor antagonist (ERA) aprocitentan in patients with resistant hypertension, showing that the drug was able to achieve a significant reduction in blood pressure over 48 weeks when added to standard therapy. The result of the 730-patient PRECISION trial puts J&J's Janssen Biotech division and Idorsia on course to bring the first drug targeting the endothelin pathway to market for this hard-to-treat patient group. They have said they plan to start filing for approval before the end of this year. It is estimated that  around 10% of the 1.3 billion people with high blood pressure around the world find it hard to control, even when using three of the current main classes of antihypertensive – diuretics, calcium channel blockers, and renin-angiotensin system-targeting drugs. According to analysts at Jefferies, that could translate to a market opportunity of around $2.5 billion a year for a drug that can help people with resistant hypertension meet their target blood pressure. In PRECISION, aprocitentan met its main objective of reducing systemic blood pressure compared to placebo, with an overall reduction of 3.8 mmHg with a daily dose of 12.5 mg aprocitentan at four weeks that wasn't improved by raising the dose to 25 mg. The effect on blood pressure was sustained out to week 40, a period in which all subjects received a 25 mg dose of the drug, according to the investigators, who have published their results in The Lancet. Between weeks 40 and 48, the difference between aprocitentan and placebo was around 5.8 mmHg. The big question facing the two companies is whether that level of improvement is enough to spur strong sales, assuming aprocitentan reaches the market. There is also some debate about the possible implications of mild-to-moderate fluid retention, which was seen in 9% of the 12.5mg group and 18% of those on 25 mg and led to seven treatment discontinuations, although the PRECISION investigators said that most cases were manageable with diuretic therapy. Idorsia chief executive Jean-Paul Clozel has described the blood pressure effect of aprocitentan as "very significant", given that 40% of patients were on triple therapy and 60% on quadruple therapy with a beta blocker added into the regimen. J&J opted into development of the drug in 2017, paying $230 million upfront for global rights on the strength of phase 2 data. Idorsia is in line for 20% royalties on annual net sales up to $500 million, 30% for $500 million to $2 billion, and 35% above that threshold. If approved, it will be Idorsia's third commercial products, after insomnia therapy Quviviq (daridorexant), which was approved in the US in January, and Pivlaz (clazosentan), an ERA for prevention of cerebral vasospasm after aneurysmal subarachnoid haemorrhage which has been approved in Japan.