Firibastat fails to improve BP in resistant hypertension: FRESH
CHICAGO — In adults with difficult-to-treat and resistant hypertension, firibastat failed to demonstrate efficacy to lower unattended office systolic BP, according to findings from the FRESH trial.
The incidence of resistant hypertension is estimated to be about 15% and is more common among Black and older adults, and those with resistant hypertension are at higher risk for poor CV outcomes, George L. Bakris, MD, professor of medicine and director of the American Heart Association-accredited Comprehensive Hypertension Center at the University of Chicago Medicine, said during a late-breaking science presentation at the American Heart Association Scientific Sessions. Firibastat (Quantum Genomics), an oral, first-in-class brain aminopeptidase A inhibitor, prevents the conversion of angiotensin II into angiotensin III at the brain level, Bakris said.
In a phase 3 study, Bakris and colleagues analyzed data from 515 adults with uncontrolled primary hypertension (systolic BP 140-179 mm Hg at screening) despite treatment with at least two classes of antihypertensive drugs. The mean age of participants was 63 years; 58.4% were men and 13.6% were Black. Researchers randomly assigned participants 500 mg firibastat twice daily or placebo in addition to background treatment for 3 months. The primary endpoint was change from baseline in unattended digital clinic systolic BP; secondary endpoints included change from baseline in unattended clinic diastolic BP and changes in 24-hour ambulatory BP.
Within the cohort, 370 participants completed study treatment.
At 3 months, there was no difference between the firibastat and placebo groups; the adjusted change from baseline in systolic automated office BP was –7.82 mm Hg for firibastat and –7.85 mm Hg for placebo, for an adjusted difference of 0.03 mm Hg (P = .98).
There were no serious, related adverse events and no observed changes in liver enzymes, Bakris said. Allergic skin reactions that had been reported in previous trials were observed in 5.1% of participants in the firibastat arm.
“Firibastat failed to demonstrate efficacy to decrease in-office, systolic BP in patients with difficult-to-treat and resistant hypertension,” Bakris said during the presentation. “Results are consistent across all subgroups and secondary endpoints.”
In light of the results of FRESH, Quantum Genomics announced that another phase 3 study of firibastat, REFRESH, has been stopped, and development of firibastat in the CV arena has ceased.
Reference:
- Quantum Genomics. www.globenewswire.com/news-release/2022/10/28/2543536/0/en/Quantum-Genomics-Announces-Lack-of-Significant-Efficacy-for-Firibastat-in-Their-Phase-III-Study-FRESH-and-is-Redirecting-to-New-Developments.html. Published Oct. 28, 2022. Accessed Nov. 11, 2022.
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Following phase 2 data that suggested its ability to lower BP effectively, firibastat failed its phase 3 trial in no uncertain terms. There was no difference in BP at 12 weeks in the participants randomized to firibastat compared with placebo. Additionally, participants randomly assigned to firibastat had a significant percentage of skin reactions (5%) compared with placebo.
It's challenging to see a viable path forward for this drug given its lack of BP-lowering efficacy with the plethora of generic options available to lower BP, newer classes under investigation that are promising (namely aldosterone synthase inhibitors and dual endothelin receptor antagonists), and the potential for FDA approval of renal denervation in the near future.
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Bakris G, et al. LBS.09: Resistant HTN: A pressure cooker. Presented at: American Heart Association Scientific Sessions; Nov. 5-7, 2022; Chicago (hybrid meeting).
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