Regulatory Decision Summary for Kerendia

This New Drug Submission (NDS) was filed to obtain market authorization pursuant to section C.08.004 of the Food and Drugs Regulations for Kerendia (finerenone) as an adjunct to standard of care therapy in adults with chronic kidney disease (CKD) and type 2 diabetes (T2D) to reduce the risks of end-stage kidney disease and a sustained decrease in estimated glomerular filtration rate, as well as cardiovascular death, non-fatal myocardial infarction and hospitalization for heart failure.

The effect of Kerendia was evaluated in two randomized, double-blind, placebo-controlled, multicenter Phase 3 studies, FIDELIO-DKD and FIGARO-DKD. In FIDELIO-DKD and FIGARO-DKD trials, a total of 6,510 patients were treated with 10 or 20 milligrams (mg) of finerenone once daily over a median duration of 2.4 and 3.6 years, respectively.

The starting dose of Kerendia was based on screening estimated glomerular filtration rate (eGFR); 10 mg once daily in patients with an eGFR of 25 to less than 60 millilitres per minute (mL/min)/1.73 metres squared (m²) of body surface area and 20 mg once daily in patients with an eGFR greater than or equal to 60 mL/min/1.73 m². The dose of Kerendia could be titrated depending on eGFR and serum potassium levels with a maximum dose of 20 mg daily.In FIDELIO-DKD, Kerendia demonstrated superiority to placebo by reducing the risk of the primary composite endpoint of time to first occurrence of kidney failure, a sustained decrease of eGFR greater than or equal to 40% from baseline over at least 4 weeks, or renal death (hazard ratio [HR] 0.82, 95% confidence interval [CI]: 0.73- 0.93, p = 0.0014). The treatment effect for the primary outcome was mainly driven by a reduction in a sustained decline in eGFR of greater than or equal to 40% (HR 0.81, 95% CI: 0.72-0.92, p = 0.0009). There were few renal deaths during the trial. Kerendia also significantly reduced the risk of the key secondary composite endpoint of time to cardiovascular (CV) death, non-fatal myocardial infarction (MI), non-fatal stroke or hospitalization for heart failure (HR 0.86, 95% CI 0.75-0.99, p = 0.034). The treatment effect on the primary and secondary composite endpoints was generally consistent across subgroups regardless of baseline characteristics.

In FIGARO-DKD, Kerendia demonstrated superiority to placebo by reducing the risk of the primary composite endpoint of time to CV death, non-fatal MI, non-fatal stroke or hospitalization for heart failure (HR 0.87, 95% CI 0.76-0.98, p = 0.0264). The treatment effect for the primary endpoint was consistent across subgroups and mainly driven by an effect on hospitalization for heart failure (HR 0.86, 95% CI 0.75-0.99, p = 0.034), though CV death also contributed to the treatment effect. A lower incidence rate of the key secondary composite outcome of time to first occurrence of kidney failure, sustained decrease of eGFR ≥40% from baseline over at least 4 weeks, or renal death was observed in the KERENDIA group compared to placebo, however this difference did not achieve statistical significance (HR 0.87, 95% CI 0.76-1.01, p = 0.0689).

The overall safety profile of Kerendia is considered acceptable for use in the patient population studied. Kerendia was generally well-tolerated, with the most common adverse event being hyperkalemia. In the pooled analysis of the two placebo-controlled studies, hyperkalemia occurred in 14% and 6.9% of Kerendia-treated versus placebo-treated patients. Hyperkalemia events were generally mild to moderate in severity, and resolved over time. Hospitalization due to hyperkalemia in the Kerendia group was 1.4% versus 0.3% in the placebo group in the FIDELIO-DKD study, and 0.6% in the Kerendia group versus less than0.1% in the placebo group in the FIGARO-DKD study. Hyperkalemia led to permanent discontinuation of treatment in 2.3% of patients receiving Kerendia versus 0.9% of patients receiving placebo in the FIDELIO-DKD study, and 1.2% of patients receiving Kerendia versus 0.4% of patients receiving placebo in the FIGARO-DKD study. Cautionary statements and risk minimization measures have been included in the Product Monograph to address safety issues and uncertainties.

The information submitted and reviewed with respect to Chemistry and Manufacturing was considered acceptable and in accordance with the Health Canada Guidance Document: Quality (Chemistry and Manufacturing) Guidance: New Drug Submissions (NDSs) and Abbreviated New Drug Submissions (ANDSs) requirement.

A Risk Management Plan (RMP) for Kerendia was submitted. Upon review, the RMP was considered to be acceptable in order to ensure that the benefit of Kerendia continues to outweigh any risk after authorization.

The overall the benefit-harm-uncertainty profile is favourable for Kerendia for the recommended indication, therefore a Notice of Compliance (NOC) pursuant to section C.08.004 of the Food and Drug Regulations was recommended.

For further details about Kerendia, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.