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Firibastat looking good for difficult-to-treat hypertension.

CHICAGO - Firibastat, a first-in-class oral antihypertensive drug, proved safe, effective, and well tolerated in NEW-HOPE, a phase 2b clinical trial focused on an understudied and underserved patient population composed largely of overweight or obese, high-risk, hypertensive racial minorities,

Firibastat is the first brain amino-peptidase A inhibitor. It selectively and specifically inhibits conversion of angiotensin II to angiotensin III, which exerts tonic stimulation over blood pressure. Decreased angiotensin III means less release of vasopressin, reduced sympathetic nervous system activity, and increased baroreflex activity, all of which add up to lower blood pressure, Keith C. Ferdinand, MD, explained at the American Heart Association scientific sessions.

NEW-HOPE (Novel Evaluation With QGC001 in Hypertensive Overweight Patients of Multiple Ethnic Origins) was an open-label multicenter study including 254 middle-aged or older hypertensive patients. Two-thirds were obese; the rest, overweight. Participants had a mean body mass index of 33 kg/[m.sup.2] and a baseline automated office blood pressure (AOBP) of 153.9/91.5 mm Hg. A total of 46% were women, and 38% were black. Indeed, blacks and other minorities made up 54% of the NEW-HOPE population.

"Minority populations in many of the clinical trials in hypertension have been underrepresented," observed Dr. Ferdinand, professor of medicine at Tulane University in New Orleans.

After a 2-week washout period, all patients were placed on firibastat at 250 mg b.i.d. for 2 weeks. If at that point their AOBP was more than 140/90 mm Hg they were bumped up to 500 mg b.i.d. Hydrochlorothiazide at 25 mg/day could be added 1 month into the trial if a patient's systolic blood pressure was 160 mm Hg or more or their diastolic blood pressure was at least 100 mm Hg. Of note, 85% of patients were able to remain on firibastat monotherapy.

The primary endpoint was change from baseline in systolic AOBP at 8 weeks. By week 8, the mean systolic blood pressure (SBP) had fallen by 9.7 mm Hg from a baseline of 153.9, which in hypertension circles is deemed a clinically meaningful improvement. Mean diastolic AOBP fell from 91.5 to 87.2 mm Hg, for a 4.3-mm Hg reduction.

"The diastolic number was smaller, but this was a middle-aged and older population, and SBP is the most important endpoint in patients of that age, not just in clinical trials but in terms of its effects on morbidity and mortality," he said.

A word about the rigorous AOBP protocol used in NEW-HOPE: It was similar to that used in the landmark SPRINT study. Patients were required to rest seated with back support in a quiet room with no talking for 5 minutes. Then six measurements were taken at 1-minute intervals, with patients' legs uncrossed and feet on the floor the whole time. The first measurement was discarded, and the next five were averaged.

In a prespecified subgroup analysis, systolic AOBP was reduced significantly more in obese than in overweight patients. Black patients averaged a 10.5-mm Hg decrease; nonblacks, a 4.1-mm Hg reduction. But black patients also averaged a 2-kg/[m.sup.2] higher body mass index.

"Firibastat had similar effects in both black and nonblack patients. And this is probably one of the main take-away points of the study: This is a drug based on the phenotype of obesity and increased blood pressure, and the drug had efficacy regardless of self-identified race," he said.

NEW-HOPE was carried out in collaboration with the Association of Black Cardiologists. Dr. Ferdinand reported serving as a consultant to Quantum Genomics and a handful of other pharmaceutical companies.

SOURCE: Ferdinand KC et al. AHA scientific sessions, Abstract LBR01.



Caption: Dr. Ferdinand

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Title Annotation:CARDIOLOGY
Author:Jancin, Bruce
Publication:Family Practice News
Geographic Code:1USA
Date:Jan 1, 2019
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