Bumetanide Nasal Spray Targets Heart Failure Edema Before IV

Esperion has launched a nationwide awareness campaign for bumetanide nasal spray (Enbumyst; Esperion), a short-term intranasal loop diuretic for edema associated with congestive heart failure (HF), which the company describes as an option for diuretic management before escalation to intravenous (IV) therapy, according to a news release.¹ The effort is timed to the January 2027 start of the CMS Ambulatory Specialty Model (ASM), a mandatory value-based payment model for specialists who treat Medicare beneficiaries with HF.

The campaign will target integrated delivery networks preparing for the ASM and provide education for nurse practitioners, physician assistants, patients, and caregivers, according to the news release. The company also plans to partner with groups such as the Heart Failure Society of America to continue generating data in HF.

Bumetanide Nasal Spray and the Ambulatory Specialty Model

An estimated 7.7 million US adults had HF from 2021 to 2023, according to the American Heart Association’s 2026 statistics update.² Under the ASM, cardiologists in selected regions who have treated at least 20 Original Medicare patients with HF in a year will face Medicare Part B payment adjustments ranging from a 9% reduction to a 9% increase in the first payment year, based on quality, cost, and other measures.³ Reducing avoidable hospitalizations is among the model’s stated goals.

“For many patients living with heart failure, worsening edema can quickly lead to an emergency department visit for IV therapy,” Andrew P. Ambrosy, MD, MPH, of Kaiser Permanente Northern California Division of Research and lead author of the product’s bioequivalence study, said in the release.¹ “Having a short-term, at-home intranasal treatment option available offers clinicians greater flexibility in how diuretic therapy can be delivered.”

Bioequivalence Data Behind the Intranasal Loop Diuretic

The FDA approved bumetanide nasal spray, developed by Corstasis Therapeutics, in September 2025 as the first intranasal loop diuretic approved in the US, indicated for edema associated with congestive HF and hepatic and renal disease in adults.⁴ Esperion closed its acquisition of Corstasis in April 2026.⁵ The recommended dosage is 0.5 mg to 2 mg once daily, and the label states that the product is not intended for chronic use and should be replaced with oral diuretics as soon as practical.⁶

Supporting data come from RSQ-777-02, a randomized, open-label, crossover study published in Circulation in which 68 healthy adults (mean age, 39 years) received 2-mg doses of nasal, oral, and IV bumetanide separated by 48-hour washout periods.^7,8 The nasal spray met its primary end point of bioequivalence to oral bumetanide, with no difference in maximum plasma concentration or area under the curve, and reached peak concentration at 1 hour vs 1.5 hours with the tablet.⁸

Urine output at 2 and 24 hours and cumulative sodium excretion did not differ across the 3 routes, and 1 case of nasal dryness was reported.⁸ Across 2 studies of 84 healthy participants, the most common adverse reactions were hypovolemia (4.8%) and headache (3%), according to the prescribing information.⁶ “[Bumetanide nasal spray] provides an innovative, non-oral method for administering loop diuretic therapy that could be used in outpatient settings,” wrote the authors of a research highlight in Heart Failure Reviews, including Ambrosy.⁸

Study Limitations and Ongoing Heart Failure Research

Because the study enrolled healthy volunteers, the reviewers noted that results may not reflect pharmacokinetics in patients with HF who have chronic kidney disease, sodium avidity, or altered drug metabolism.⁸ They also wrote that diuretic resistance in most patients stems from blockade at the kidney level, which changing the route cannot overcome, and that nasal congestion and variable spray technique could affect absorption.⁸

Studies in patients with HF are underway. The phase 4 VAPOR-HF trial (NCT07375212) is evaluating whether a single 4-mg intranasal dose acutely reduces pulmonary artery pressure and blood volume in outpatients with HF who have implanted remote monitoring devices.⁹

“Future prospective, adequately powered, randomized studies in HF populations should be conducted to evaluate whether the intranasal application of bumetanide will benefit [patients with HF],” the reviewers concluded.⁸

References

1. Esperion Therapeutics offers short-term option for diuretic management before escalation to IV for patients with heart failure. News release. Esperion Therapeutics. September 30, 2026. Accessed October 7, 2026. https://www.esperion.com/news-releases/news-release-details/esperion-therapeutics-offers-short-term-option-diuretic

2. Palaniappan LP, Allen NB, Almarzooq ZI, et al; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Committee. 2026 Heart disease and stroke statistics: a report of US and global data from the American Heart Association. Circulation. 2026;153(9):e275-e906. doi:10.1161/CIR.0000000000001412

3. Ambulatory Specialty Model: model overview fact sheet. CMS Innovation Center. Accessed October 7, 2026. https://www.cms.gov/files/document/asm-model-fact-sheet.pdf

4. Corstasis Therapeutics announces FDA approval of Enbumyst (bumetanide nasal spray) for the treatment of edema associated with congestive heart failure, liver disease and kidney disease. News release. Corstasis Therapeutics. September 15, 2025. Accessed October 7, 2026. https://www.businesswire.com/news/home/20250915243998/en/Corstasis-Therapeutics-Announces-FDA-Approval-of-ENBUMYST-bumetanide-nasal-spray-for-the-Treatment-of-Edema-Associated-with-Congestive-Heart-Failure-Liver-Disease-and-Kidney-Disease

5. Esperion Therapeutics closes acquisition of Corstasis Therapeutics, expanding its cardiovascular franchise with Enbumyst (bumetanide nasal spray). News release. Esperion Therapeutics. April 2, 2026. Accessed October 7, 2026. https://www.esperion.com/node/18751

6. Enbumyst. Prescribing information. Corstasis Therapeutics; 2025. Accessed October 7, 2026. https://www.drugs.com/pro/enbumyst.html

7. Ambrosy AP, Bensimhon D, Bernstein G, et al. Randomized study comparing a novel intranasal formulation of bumetanide with oral and intravenous formulations. Circulation. 2025;151(10):737-740. doi:10.1161/CIRCULATIONAHA.124.072949

8. Biegus J, Ponikowska B, Canonico ME, Damman K, Palazzuoli A, Ambrosy AP. Bumetanide nasal spray: a novel approach to enhancing diuretic response and advancing ambulatory heart failure care? Heart Fail Rev. 2025;30(5):1123-1126. doi:10.1007/s10741-025-10517-y

9. VAPorized administration of bumetanide for outpatient relief in heart failure (VAPOR-HF). ClinicalTrials.gov. Updated January 29, 2026. Accessed October 7, 2026. https://clinicaltrials.gov/study/NCT07375212