By: Urooj K. Malik, PharmD Candidate c/o 2024

Effective September 22, 2023, the United States (U.S.) Food and Drug Administration (FDA) granted approval for empagliflozin (Jardiance®) 10 mg tablets for the treatment of adults with chronic kidney disease (CKD) at risk of progression. This decision was based on the results of the EMPA-KIDNEY phase III trial that demonstrated that Jardiance significantly reduced the risk of kidney disease progression, cardiovascular death, and hospitalization in adults diagnosed with CKD.¹

CKD is a condition where the kidneys become damaged over time and lose their ability to filter waste products from the blood. This condition typically develops slowly, with few symptoms experienced at first. CKD increases the likelihood of experiencing additional health complications, including heart disease and stroke.² Though CKD can develop at any age, some common risk factors include diabetes, hypertension, obesity, and smoking. This recent approval holds great significance as it adds to the treatment options for the over 35 million adults in the U.S. affected by CKD.¹

EMPA-KIDNEY Trial Overview

EMPA-KIDNEY was a phase III, randomized, double-blind, placebo-controlled clinical trial conducted globally in Europe, North America, and East Asia.³ This study was sponsored by Boehringer Ingelheim and funded by Boehringer Ingelheim and Eli Lilly and Company. The primary outcome of this study was a composite of the progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in estimated glomerular filtration rate (eGFR) to less than 10 mL/min/1.73 m², a sustained reduction in eGFR of at least 40% from baseline, or death from renal causes) or death from cardiovascular causes.³ Secondary outcomes included a composite of hospitalization for heart failure or death from cardiovascular causes, hospitalization for any reason, and death from any cause.³ Participants were included in this trial if they were 18 years of age or above and were diagnosed with CKD with a risk of kidney disease progression at least three months before and at the time of the screening visit.⁴

Participants were also included if they were taking clinically appropriate doses of a single agent renin-angiotensin-system (RAS)-inhibitor with either an angiotensin-converting enzyme (ACE) inhibitor or angiotensin 2-receptor blocker (ARB) unless these treatments were either not tolerated or indicated.³ However, patients were excluded if they had both type 2 diabetes and prior atherosclerotic cardiovascular disease with eGFR above 60 mL/min/1.73 m², type 1 diabetes, functioning scheduled kidney transplant, dialysis, polycystic kidney disease, recent history of intravenous immunosuppressive therapy or greater than 45 mg of prednisone or equivalent for kidney disease.⁴

Participants were randomized to receive either Jardiance 10 mg orally once a day or a matching placebo. Follow-up was completed over a median span of 2 years.³

6,609 participants partook in the trial, with 3,304 in the Jardiance group and 3,305 in the placebo group. Jardiance demonstrated a 28% relative risk reduction, with an absolute risk reduction of 3.6% per patient-year at risk, compared to placebo, both given on top of standard care, for the composite primary endpoint of kidney disease progression or cardiovascular death.³ The event rate in the Jardiance group was 13.1% (432 out of 3,304) and 16.9% (558 out of 3,305) in the placebo group.³ The trial was stopped early due to evidence of efficacy, and results were reported in November 2022.⁵ This study was the first sodium-glucose cotransporter-2 (SGLT2) inhibitor CKD trial that demonstrated a statistically significant reduction in the risk of first and recurrent hospitalization, with a 14% relative risk reduction with Jardiance versus placebo. 1,611 hospitalizations occurred among 960 patients in the Jardiance group, and 1,895 hospitalizations occurred among 1,035 patients in the placebo group.¹

However, Jardiance is contraindicated in specific patient populations, including those with type 1 diabetes and individuals with severe kidney problems, because of Jardiance’s potential to increase the risk of diabetic ketoacidosis. Jardiance is not recommended to improve glycemic control in type 2 diabetes patients with an eGFR less than 30 mL/min/1.73 m² or for treating CKD in patients with polycystic kidney disease.³

Implications on Pharmacy Practice

Overall, the approval of Jardiance for CKD reflects a positive development for the pharmaceutical industry, namely for Boehringer Ingelheim and Eli Lilly, the companies behind Jardiance. In a press release, Leonard Glass, senior vice president of Diabetes Global Medical Affairs at Eli Lilly, stated, “Following previous indications for [empagliflozin] in heart failure and [type 2 diabetes], this FDA approval now provides physicians, including nephrologists, with an important treatment option for adults living with CKD at risk for progression.”⁶ This approval allows for a new treatment option that has the potential to reduce the risk of kidney function decline, cardiovascular complications, and hospitalizations.

“The meaningful benefits that empagliflozin demonstrated in the EMPA-KIDNEY phase III trial are welcome news for adults living with CKD in this country,” stated Katherine Tuttle, M.D., Executive Director for Research, Providence Inland Northwest Health, Regional Principal investigator for the Institute of Translational Health Sciences and Professor of Medicine at the University of Washington, and EMPA-KIDNEY steering committee member.¹ However, due to the contraindications, caution is warranted in identifying eligible patient populations who can be initiated on this medication. Healthcare providers are tasked with carefully reviewing patient profiles when prescribing Jardiance. The approval of Jardiance demonstrates the potential to improve the quality of life for CKD patients.

References

1. US FDA approves Jardiance® for the treatment of adults with chronic kidney disease. News release. Eli Lilly and Company. Published September 22, 2023. Accessed December 20, 2023. https://investor.lilly.com/node/49606/pdf
2. Chronic kidney disease (CKD). National Kidney Foundation. https://www.kidney.org/atoz/content/about-chronic-kidney-disease
3. The EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, et al. Empagliflozin in Patients with chronic kidney disease. N Engl J Med. 2023;388(2):117-127. doi:10.1056/NEJMoa2204233
4. EMPA-KIDNEY (The Study of Heart and Kidney Protection With Empagliflozin). Clinicaltrials.gov identifier: NCT03594110. Updated August 3, 2023. Accessed January 6, 2024. https://clinicaltrials.gov/ct2/show/NCT03594110
5. Jardiance® phase III EMPA-KIDNEY trial will stop early due to clear positive efficacy in people with chronic kidney disease. Eli Lilly and Company. Published March 16, 2022. Accessed January 6, 2024. https://investor.lilly.com/news-releases/news-release-details/jardiancer-phase-iii-empa-kidney-trial-will-stop-early-due-clear
6. U.S. FDA approves Jardiance® for treatment of adults with chronic kidney disease. Boehringer Ingelheim. Published September 21, 2023. Accessed January 6, 2024. https://www.boehringer-ingelheim.com/fda-approves-jardiance-treatment-chronic-kidney-disease

Published by Rho Chi Post