A new class of drugs, the BAPAIs, targeting a previously unused pathway in arterial hypertension and possibly complementary to those currently targeted, brings hope for difficult-to-treat patients.
A new class of antihypertensives, that of the BAPAIs, has obtained its validation at the American Congress of Cardiology, the American Heart Association, in Chicago.
It had been more than 30 years since a new molecule had been found in the treatment of arterial hypertension, a frequent disease where many patients do not meet the objectives defined by the consensus, and where new therapeutic associations must be put in place. By blocking aminopeptidases-A in the brain, this treatment may complement current treatments and improve the treatment of difficult-to-treat high blood pressure.
Many badly treated patients
Paradoxically for such a frequent and well-known disease, the needs remain glaring in the treatment of arterial hypertension: more than 30% of patients remain difficult to treat and nearly 50% of them do not meet the objectives, in despite treatment sometimes combining 3 molecules.
Obesity, sensitivity to salt, certain ethnic groups whose pathways involved in hypertension are not the same as usual (low renin activity)…, compromise the effectiveness of current treatments.
A new target in the brain
There is a renin-angiotensin system in the brain and one of these moieties, angiotensin III, is one of the most potent peptides in arterial tone.
This peptide contributes to an increase in blood pressure by three different mechanisms: increase in the concentration of vasopressin, increase in the activity of sympathetic neurons associated with vasoconstriction of the vessels, and baroreflex inhibition.
An aminopeptidase A inhibitor
Firibastat is the first inhibitor of cerebral aminopeptidases-A, and it inaugurates the class of BAPAI (Brain AminoPeptidase A Inhibition) with a completely original mechanism of action in hypertension: it acts only on the brain and not on the peripheral organs like other conventional anti-hypertensives.
This small molecule, administered orally in the form of a pro-drug, is capable of penetrating the brain and selectively inhibiting cerebral aminopeptidase A, which will block the transformation of angiotensin II into angiotensin III and reduce the release of vasopressin and sympathetic activity, as well as improving the baroreflex response.
A validation study
New-Hope is a phase II study carried out on 218 hypertensive patients, including many patients at risk and at least 50% black and Hispanic, ethnic groups usually under-represented in studies while resistance to treatment is frequent. . It was conducted with an automated blood pressure measurement, which is now the reference method.
At 8 weeks of treatment, a significant decrease in blood pressure is observed: systolic blood pressure has dropped by 9.7 mm Hg (p<0.0001) and diastolic by 4.3 mm Hg (p<0.0001). It is, moreover, a consistent decline regardless of the type of patient and race. Tolerance was good, with no particular neuropsychiatric effects.
There is now a new therapeutic pathway in hypertension, complementary to the other metabolic pathways used by current treatments. It remains to specify the best methods of association in order to be able to better treat patients who are difficult to treat.
Interview with Fabrice Balavoine, Vice-President research and Development, Quantum Genomics
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