Fine Lennon slows the progression of CVD and reduces CV events, the study says

Even with the latest breakthrough treatments for chronic kidney disease (CKD), there remains an unfulfilled high need to combat this global problem, researchers are investigating on Friday. He said while presenting the end-stage results of oral first-in-class medications. American Society of Nephrology Kidney Week..

The results of the drug Finelenone were published at the same time New England Journal of Medicine.. Dr. Rajiv Agarwal, MD, MS, FASN, a professor of medicine at Indiana University School of Medicine and a staff doctor at Veterans Affairs Medical, said he delayed the time to progression of CKD by 18% and reduced cardiovascular events by 14% compared to placebo. Stated. Center in Indianapolis, Indiana.

Finelenone targets overactivation of mineralocorticoid receptors and, when sent to overdrive, promotes further inflammation and fibrosis in patients with CKD and type 2 diabetes (T2D).

The study, FIDELIO-DKD, a finelenone that reduces renal failure and disease progression in diabetic nephropathy, was conducted in 48 countries and in more than 1000 institutions. The final analysis included 5674 patients. Patient eligibility criteria include one of the following:

• Urinary albumin to creatinine ratio (albumin measured in milligrams, creatinine measured in grams) is less than 30-300
• Estimated glomerular filtration rate (eGFR) of less than 25-60 ml / min per 1.73 m² Of body surface area
• Serum potassium with serum potassium levels below 4.8 mmol per liter
• Diabetic retinopathy

Or:

• Urinary albumin to creatinine ratio 300-5000, eGFR 25-75 ml / min / less than 1.73 m²..

Agarwal said these patients, with an average age of 65, had moderate to advanced kidney disease. Patient characteristics included a mean eGFR44, with a median ratio of urinary albumin to creatinine in more than half 850. Mean glycated hemoglobin (A1C) was 7.7 in both patient groups. The majority of people using drugs to lower glucose used insulin and other analogs.

The primary combined outcome focused on time to renal failure, a persistent reduction in eGFR from baseline by at least 40%, or death from renal impairment. The secondary compound outcome was cardiovascular: The outcome was cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure.

The median follow-up was 2.6 years.

During the break-in period, all patients were pre-treated with a maximum tolerated ACEi or ARB for at least 4 weeks (up to 16 weeks).

After the break-in period, patients were randomly assigned in a 1: 1 ratio to receive oral fillenone (n = 2833) or placebo (n – 2841). Patients with eGFR <25-60 ml / min / 1.73 m² At the time of the screening visit, he received a starting dose of 10 mg once daily.

eGFR of 60 ml / min per 1.73 m² At the time of screening, he received an initial dose of 20 mg or more once daily. If the serum potassium level was 4.8 mmol or less per liter and the eGFR was stable, it was recommended to increase the dose from 10 mg to 20 mg once daily after 1 month.

Looking at the changes in albuminuria, he said, finelenone resulted in a 31% reduction at 4 months compared to placebo. By 36 months, it narrowed slightly and decreased by about 25%.

In the finelenone group, 504 patients progressed to renal failure, whereas in placebo 600 patients decreased by 18% (HR, 0.82; 95% CI, 0.73 to 0.93; P = .001).

Looking at the secondary outcome, the drug reduced the risk of CV events: 13%, or 367 patients (hr, 0.86;) in finelenone compared to 14.8% or 420 patients in the placebo group. 95% CI, 0.75-0.99; p = .03).

When needed to be treated by number, Agarwal said that 29 patients need to be treated to prevent one kidney-related event and 42 patients need to be treated to prevent one CV event. It was.

Overall, the frequency of adverse events was similar between finelenone and placebo. The number of adverse events leading to study drug discontinuation was higher in finelenone, which was primarily hyperkalemia (51 compared to placebo 19) and increased serum potassium (13 compared to placebo 6). It was. The average increase in potassium was 0.2 mmol / L across the subpopulation compared to placebo.

He added that the discontinuation rate for other classes of investigational drugs that did not provide renal or cardiac protection due to hyperkalemia was much higher, he added, that there were no deaths or low doses of AE leading to permanent discontinuation.

The study, funded by Bayer, said it plans to submit a Finnerenon New Drug Application (NDA) to the FDA by the end of 2020 on Friday.

reference

Bakris GL, Agarwal R, Anker SD and more. Effect of finelenone on the outcome of chronic kidney disease in type 2 diabetes. Published online on October 23, 2020. New Engl J Med.. Doi: 10.1056 / NEJMoa2025845