In the JournalsPerspective

NEW HOPE: Firibastat lowers BP in high-risk population

Keith C. Ferdinand
Keith C. Ferdinand

The novel aminopeptidase A inhibitor firibastat was associated with BP reduction at 8 weeks in a high-risk diverse patient population, according to the results of the phase 2 NEW HOPE study.

As Cardiology Today previously reported, firibastat (Quantum Genomics) selectively blocks aminopeptidase A, which converts angiotensin II to angiotensin III in the brain, and may be suitable for patients with low renin concentration and higher vasopressin effects.

For the open-label NEW HOPE study, the researchers enrolled 256 high-risk patients with hypertension. All were overweight or obese and 54% were black or Hispanic.

After a 2-week washout period, all patients received firibastat 250 mg twice daily for 8 weeks. The dose was raised to 500 mg twice daily if BP remained more than 140/90 mm Hg at 2 weeks, and hydrochlorothiazide 25 mg once daily was added at 1 month if BP remained more than 160/110 mm Hg.

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

Among the cohort, 85% did not require the addition of hydrochlorothiazide, Keith C. Ferdinand, MD, FACC, FAHA, professor of medicine at Tulane University School of Medicine and a Cardiology Today Editorial Board Member, and colleagues wrote.

At 8 weeks, treatment with firibastat lowered systolic BP by 9.5 mm Hg (P < .0001) and diastolic BP by 4.2 mm Hg (P < .0001), according to the researchers.

The treatment effect was consistent across all subgroups regardless of age, sex, BMI and race, including systolic BP reductions of 10.2 mm Hg in patients with obesity, 10.5 mm Hg in black patients and 8.9 mm Hg in non-black patients (P < .0001 for all), Ferdinand and colleagues wrote.

The most frequent adverse events were headaches (4%) and skin reactions (3%), and there were no cases of angioedema, according to the researchers.

The novel aminopeptidase A inhibitor firibastat was associated with BP reduction at 8 weeks in a high-risk diverse patient population, according to the results of the phase 2 NEW HOPE study.
Source: Adobe Stock

The drug also did not affect potassium, sodium and creatinine levels.

“The results reported here are a useful guide to the design of a larger, randomized parallel-group trial to investigate the use of firibastat as add-on therapy to complex drug regimens for the treatment of difficult-to-treat or potentially resistant [hypertension] in order to improve BP control and, ultimately, reduce morbidity and mortality rates among high-risk patients,” Ferdinand and colleagues wrote. – by Erik Swain

Disclosures: Ferdinand reports he has received grant and/or research support from Boehringer Ingelheim and served as a consultant for Amgen, Boehringer Ingelheim, Novartis, Quantum Genomics and Sanofi. Please see the study for the other authors’ relevant financial disclosures.

Keith C. Ferdinand
Keith C. Ferdinand

The novel aminopeptidase A inhibitor firibastat was associated with BP reduction at 8 weeks in a high-risk diverse patient population, according to the results of the phase 2 NEW HOPE study.

As Cardiology Today previously reported, firibastat (Quantum Genomics) selectively blocks aminopeptidase A, which converts angiotensin II to angiotensin III in the brain, and may be suitable for patients with low renin concentration and higher vasopressin effects.

For the open-label NEW HOPE study, the researchers enrolled 256 high-risk patients with hypertension. All were overweight or obese and 54% were black or Hispanic.

After a 2-week washout period, all patients received firibastat 250 mg twice daily for 8 weeks. The dose was raised to 500 mg twice daily if BP remained more than 140/90 mm Hg at 2 weeks, and hydrochlorothiazide 25 mg once daily was added at 1 month if BP remained more than 160/110 mm Hg.

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

Among the cohort, 85% did not require the addition of hydrochlorothiazide, Keith C. Ferdinand, MD, FACC, FAHA, professor of medicine at Tulane University School of Medicine and a Cardiology Today Editorial Board Member, and colleagues wrote.

At 8 weeks, treatment with firibastat lowered systolic BP by 9.5 mm Hg (P < .0001) and diastolic BP by 4.2 mm Hg (P < .0001), according to the researchers.

The treatment effect was consistent across all subgroups regardless of age, sex, BMI and race, including systolic BP reductions of 10.2 mm Hg in patients with obesity, 10.5 mm Hg in black patients and 8.9 mm Hg in non-black patients (P < .0001 for all), Ferdinand and colleagues wrote.

The most frequent adverse events were headaches (4%) and skin reactions (3%), and there were no cases of angioedema, according to the researchers.

The novel aminopeptidase A inhibitor firibastat was associated with BP reduction at 8 weeks in a high-risk diverse patient population, according to the results of the phase 2 NEW HOPE study.
Source: Adobe Stock

The drug also did not affect potassium, sodium and creatinine levels.

“The results reported here are a useful guide to the design of a larger, randomized parallel-group trial to investigate the use of firibastat as add-on therapy to complex drug regimens for the treatment of difficult-to-treat or potentially resistant [hypertension] in order to improve BP control and, ultimately, reduce morbidity and mortality rates among high-risk patients,” Ferdinand and colleagues wrote. – by Erik Swain

Disclosures: Ferdinand reports he has received grant and/or research support from Boehringer Ingelheim and served as a consultant for Amgen, Boehringer Ingelheim, Novartis, Quantum Genomics and Sanofi. Please see the study for the other authors’ relevant financial disclosures.

    Perspective

    The mechanism of action of this drug is novel and intriguing. There was no placebo or usual-care control, so that is a significant limitation. These findings need to be replicated in a randomized controlled trial. However, the results to appear to be significant in terms of the ability of firibastat to lower BP in a diverse population with stage 2 hypertension, and the effects looks to be additive to hydrochlorothiazide. This is a potentially useful approach that is definitely worth pursuing in a rigorous randomized controlled design.

    The ultimate goal is to provide another agent to be used for treatment of resistant hypertension, but this study does not go far enough to say whether firibastat might be a candidate in that population. The population in this study did not meet the definition of resistant hypertension.

    • Robert M. Carey, MD, MACP, FRCPI, FAHA
    • Professor of Medicine
      Dean, Emeritus, School of Medicine
      Division of Endocrinology and Metabolism
      Department of Medicine
      University of Virginia Health System

    Disclosures: Carey reports no relevant financial disclosures.