Baxdrostat

By Pushkala Aripaka Bengaluru: AstraZeneca plans to file for regulatory approval of its experimental blood pressure treatment before the end of the year, a senior company executive said, about a product seen as key to the drugmaker's long-term sales strategy. The company is aiming for potential approvals in 2026 for the drug, baxdrostat , starting with the U.S. and the EU, said Ruud Dobber, president of AstraZeneca's biopharmaceuticals unit, ahead of a presentation of advanced trial data at a medical conference on Saturday. Baxdrostat targets blood pressure-regulating hormone aldosterone, a novel approach compared with older treatments like diuretics and ACE inhibitors, which do not address hormonal drivers. AstraZeneca expects peak annual sales for the drug to exceed $5 billion. Keenly watched data showed that 2mg of baxdrostat, added to standard treatment, reduced systolic blood pressure by 9.8 millimetres of mercury (mmHg) from the baseline at 12 weeks, when adjusted for placebo, in patients with hard-to-control hypertension. At the 1mg dose, that pressure exerted on the arteries by the heart's pumping action was lowered by 8.7 mmHg. Physicians polled by TD Cowen wished to see a 10-12 mmHg fall in placebo-adjusted blood pressure, the brokerage said on Friday. Mineralys Therapeutics ' rival drug, lorundrostat, in March showed a placebo-adjusted reduction in systolic blood pressure by 9.1 mmHg at six weeks with a 50mg dose. The U.S. company also expects to submit data to the FDA by year-end. "There's a huge acknowledgement that hypertension needs to be treated in a much more aggressive way," Dobber said. High blood pressure affects over 1 billion people, according to the World Health Organization, and aggravates risk of heart attacks or strokes. A small percentage of patients - 1.1% - taking baxdrostat developed hyperkalaemia , marked by high potassium levels in the blood. Hyperkalaemia was also observed with Mineralys' lorundrostat. (Reporting by Pushkala Aripaka in Bengaluru; Editing by Sahal Muhammed)

AstraZeneca plans to seek regulatory approval for its experimental hypertension drug baxdrostat "in the months ahead," following detailed Phase III results that showed the treatment significantly reduced blood pressure in patients with stubbornly high hypertension.The results, presented Saturday at the European Society of Cardiology (ESC) congress and simultaneously published in the NEJM, mark the first detailed look at how the oral once-daily therapy could measure up against Mineralys Therapeutics' rival late-stage contender in the same drug class.The BaxHTN study, which was toplined in July, enrolled 794 patients whose hypertension had proven difficult to manage despite multiple therapies. The trial met its primary and all secondary endpoints.Global 'gamechanger'After 12 weeks, patients receiving baxdrostat on top of background therapy experienced sharp declines in systolic blood pressure: a 15.7 mmHg average drop from baseline in seated systolic blood pressure (SBP) at the 2-mg dose, equivalent to a placebo-adjusted decline of 9.8 mmHg, and a decrease of 14.5 mmHg at the 1-mg dose, or 8.7 mmHg versus placebo."I've never seen blood pressure reductions of this magnitude with a drug," said Bryan Williams, the trial's principal investigator. The nearly 10 mmHg placebo-adjusted reduction, he said, is "linked to substantially lower risk of heart attack, stroke, heart failure and kidney disease," adding the data "show that aldosterone plays a greater role in hard-to-control hypertension than previously recognised.""I think this could be a gamechanger in the way we approach difficult to control or hard-to-control blood pressure," Williams said. "The results suggest that this drug could help up to half a billion people globally."AstraZeneca said SBP reductions were consistent across both resistant and uncontrolled subgroups and extended to diastolic pressure. Additionally, roughly 40% of patients receiving either the 1-mg or 2-mg dose achieved a controlled seated SBP of <130 mm Hg at week 12, more than double the 18.7% who did so on placebo.Safety was also favourable, with few cases of hyperkalaemia and no unexpected signals, according to the company.Broader ambitionsMina Makar, the company's senior vice president for global cardiovascular, renal and metabolism, has framed the BaxHTN results as a validation of aldosterone synthase inhibition, and expressed optimism about the potential of baxdrostat, which AstraZeneca acquired via its $1.3-billion CinCor takeout in 2023."It's not just about a single molecule — it's the foundation of a broader portfolio," he told FirstWord in July. "We believe baxdrostat could also offer benefits in heart failure and chronic kidney disease. We now have a substantial development programme under way, including seven Phase III trials across four indications. This is just the beginning." For the rest of that interview, see – ViewPoints: AstraZeneca's Mina Makar on baxdrostat's Phase III win and potential practice-changing status.Lorundrostat's deltaMeanwhile, Mineralys is pushing forward with lorundrostat, a competing aldosterone synthase inhibitor that delivered positive pivotal data from two Phase III studies earlier this year. That drug demonstrated an 11.7 mmHg placebo-adjusted reduction at the 12-week mark. Prior to Saturday's BaxHTN readout, Jefferies analysts said that if baxdrostat's placebo-adjusted delta fell somewhere between 9.7 and 13.7 mmHg, the results "should be considered broadly in-line" with Mineralys' agent.Attention now turns to Bax24, a Phase III study evaluating 24-hour ambulatory effects of baxdrostat, which AstraZeneca expects to report later this year. In addition to positioning the drug both as a standalone therapy, Makar indicated that the drug is also being developed in fixed-dose combinations with AstraZeneca's SGLT2 inhibitor Farxiga (dapagliflozin).