AstraZeneca announced a promising start for new drug candidate ‘Baxdrostat’, which has been chosen as the next runner up to succeed ‘Forxiga’ (ingredient: dapagliflozin).
On the 2nd, the New England Journal of Medicine (NEJM), an international academic journal, published the results of a phase 2 clinical trial of ‘Boxdrostat’ for treatment-resistant hypertension.
AstraZeneca announced the acquisition of CinCor, a US pharmaceutical company, in early January. Vaxdrostat is a candidate substance that Synco was developing as a treatment for the heart and kidneys, and AstraZeneca expects it to be the next runner to lead the company’s CVRM (Cardiovascular, Renal, Metabolism) division following Forxiga.
Baxdrostat is an oral small molecule inhibitor that is highly selective for aldosterone synthase, the enzyme responsible for the synthesis of aldosterone in the adrenal gland.
Aldosterone synthase has been considered a promising pharmacological target for the treatment of hypertension over the past decades. However, since the synthesis of cortisol, another hormone released by the adrenal cortex, is catalyzed by another enzyme that shares 93% genetic sequence similarity with aldosterone synthase, selective inhibition of aldosterone is difficult to achieve. synthase left as task.
Baxdrostat demonstrated 100:1 selectivity for aldosterone synthase inhibition in preclinical and phase 1 studies and reduced plasma aldosterone levels at multiple doses, but not cortisol levels.
So, in a phase 2 study, the research team randomly assigned 3 doses (0.5 mg, 1 mg, 2 mg) of boxdrostat and placebo to more patients and administered them (administered orally once a day) after 12 weeks by changes in systolic blood. Efficacy and safety as an antihypertensive drug were evaluated.
The patients included in the study were treatment-resistant hypertensive patients with blood pressure of 130/80 mmHg or higher despite taking the first three antihypertensive drugs, including diuretics.
A total of 248 patients completed the study. At week 12 of administration, the changes in systolic blood pressure from baseline in the 2 mg, 1 mg, and 0.5 mg dose groups and the placebo group were −20.3 mmHg, −17.5 mmHg, −12.1 mmHg, and −9.4 mmHg, respectively.
Vaxdrostat 2 mg and 1 mg reduced systolic blood pressure by 11 mmHg and 8.1 mmHg, respectively, compared to placebo, and these values were statistically significant.
No deaths occurred during the study period, no serious side effects were reported with Boxdrostat, and no cases of adrenocortical insufficiency occurred.
Potassium levels associated with boxdrostat increased to more than 6 mmol per liter in two patients, but this increase did not occur again after the drug was discontinued and restarted.
The research team said, “In patients with treatment-resistant hypertension, inhibition of aldosterone synthase by daily administration of 1 mg or 2 mg of boxdrostat resulted in significantly greater reductions in systolic blood pressure at 12 weeks compared with dependent placebo, ” he concludes.
Meanwhile, although antihypertensive drugs of different mechanisms have been developed, it is known that about 20% of hypertensive patients undergoing drug treatment are resistant hypertensive patients.
In general, patients with resistant hypertension are at high risk of cardiovascular events, and some are more likely to have secondary causes of hypertension, requiring specialist intervention and aggressive drug treatment for blood pressure control.
