Baxdrostat

As it prepares for an eventual pitch to regulators, Mineralys Therapeutics reported new data showing that its experimental drug lorundrostat significantly lowered blood pressure in patients with chronic kidney disease (CKD). The findings add to a growing body of evidence for the oral aldosterone synthase inhibitor, which had already hit key goals in two pivotal hypertension trials earlier this year.In the Phase II Explore-CKD study reported Tuesday, lorundrostat was added to background treatment – such as SGLT2 inhibitors and ACE inhibitors or angiotensin receptor blockers (ARBs) – in CKD patients with albuminuria. After four weeks, lorundrostat reduced systolic blood pressure by 9.3 mmHg compared to baseline, representing a statistically significant 7.5 mmHg placebo-adjusted reduction, meeting the primary endpoint.The crossover study also demonstrated a placebo-adjusted 25.6% reduction in urine albumin-to-creatinine ratio (UACR), a marker of kidney function that suggests potential renal protective effects, the company said."Along with the successful pivotal trials, Launch-HTN and Advance-HTN, and the ongoing open-label extension trial, these results comprise the core package for our planned NDA submission," said CEO Jon Congleton. Jefferies analysts have said they expect Mineralys to file for FDA approval next year and predict a 2027 launch.The Explore-CKD study builds results from two pivotal hypertension trials that sent Mineralys shares up 42% in March. The Phase III Launch-HTN trial showed lorundrostat achieved an 11.7 mmHg reduction in systolic blood pressure at 12 weeks, while the Phase II Advance-HTN study demonstrated a 7.9 mmHg reduction.On the safety front, three patients (5%) in the CKD trial saw increases in potassium levels during lorundrostat treatment compared with none on placebo. Treatment emergent adverse events (TEAEs) leading to discontinuation occurred in two patients (3%) during lorundrostat treatment and one (2%) on placebo.Kidney function, measured by estimated glomerular filtration rate (eGFR), also declined slightly (-6.8% compared to -2.2% for placebo) – an effect seen with other renin-angiotensin-aldosterone pathway inhibitors like ACE inhibitors, ARBs and mineralocorticoid antagonists, according to the company. "This is the result of a reduction in the deleterious over-perfusion of glomeruli due, in part, to reduced blood pressure," it said.A recent FirstWord poll of US cardiologists suggested there was cautious optimism about lorundrostat, but doctors flagged the need for potassium monitoring and a clean safety profile as key factors that would influence how widely the drug is adopted.Meanwhile, Mineralys faces possible competition down the road from AstraZeneca, which is developing a similar drug, baxdrostat, acquired in its $1.8-billion takeover of CinCor in 2023. That candidate is in Phase III testing."While we don't see a major debate on demand – both primary care and cardios may be interested – there's debate around access and how quickly Mineralys' drug would be adopted," Jefferies analysts said in a note to clients earlier this month. "Ultimately, Mineralys will be covered, but likely through multiple barriers like step edits, quantity limits, etc., and competitor AstraZeneca could launch around the same time with more marketing and commercial presence."For more, see – KOL Views Q&A: How Mineralys' pivotal wins swing ASI vs MRA battle in resistant hypertension.