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Aminopeptidase A inhibitor shows promise for BP lowering in high-risk patients

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Keith C. Ferdinand

NEW ORLEANS — Firibastat, a novel aminopeptidase A inhibitor, may be an effective treatment tool to lower BP in high-risk patients, including those of certain racial/ethnic minorities, Keith C. Ferdinand, MD, FACC, FAHA, told the audience at the Vascular Biology Working Group.

“The mechanism of action is to block aminopeptidase A, which converts angiotensin II to angiotensin III. It’s an orally active, brain-penetrating drug that leads to the active compound that specifically blocks aminopeptidase A,” Ferdinand, a Cardiology Today Editorial Board Member, said here. 

Because of that mechanism, firibastat (Quantum Genomics) may be effective in patients with low renin concentration and higher vasopressin effects, he said.

For the phase 2b NEW-HOPE study, researchers evaluated firibastat in 254 patients with hypertension at high risk for CV events. Patients had a mean age of 58 years, 46% were women, 54% were of minority race/ethnicity, 65% were obese and 28% had type 2 diabetes.

“The main priority was to study a population in which monotherapy with ACE inhibitors and angiotensin receptor blockers has shown less robust blood pressure lowering,” Ferdinand said.

Firibastat, a novel aminopeptidase A inhibitor, may be an effective treatment tool to lower BP in high-risk patients, including those of minority races and ethnicities, Keith C. Ferdinand, MD, FACC, FAHA, told the audience at the Vascular Biology Working Group.

Source: Adobe Stock

At baseline, all patients had systolic BP 145 mm Hg to 170 mm Hg.

The primary endpoint was automated office systolic BP at 8 weeks.

While patients could be uptitrated from a 250-mg twice daily dose to a 500-mg twice daily dose of firibastat and have hydrochlorothiazide added to their regimen if necessary, most patients were able to remain on monotherapy, Ferdinand said.

At 8 weeks, automated office systolic BP declined from 155 mm Hg to 144.4 mm Hg (change, –9.5 mm Hg; P < .0001), he said.

Automated office diastolic BP dropped 4.2 mm Hg at 8 weeks (P < .0001), according to the researchers.

24-hour ambulatory systolic BP also declined.

“In a multivariate analysis, the only predictor of effect was higher blood pressure,” Ferdinand said.

The treatment effect did not differ by age, sex, BMI, race/ethnicity or kidney function, he said, though he noted a trend toward a greater effect in black patients than in non-black patients.

The most common adverse effects were headaches and skin reactions, Ferdinand said.

“NEW-HOPE was a first-of-its kind study in a high-risk, diverse population,” he said. “Aminopeptidase A inhibition may be more effective at BP lowering in this population than what has been seen with other monotherapies. NEW-HOPE supports further study to investigate firibastat in patients with difficult-to-treat or resistant hypertension. We are in the process of designing these studies.” – by Erik Swain

Reference:

Ferdinand KC. Session II: New Treatment Strategies. Presented at: Vascular Biology Working Group; March 15, 2019; New Orleans.

Disclosures: The study was sponsored by Quantum Genomics. Ferdinand reports he is a consultant for Amgen, Boehringer Ingelheim, Novartis, Quantum Genomics and Sanofi.