Bayer's First-in-Class Drug Kerendia (Finerenone) Receives Positive CHMP Opinion in EU and Under Regulatory Review in China for Diabetic Kidney Disease
Dec 21, 2021 01:46
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01:46
Bayer
Pharmaceutical Product R&D Developer
Committee for Medicinal Products for Human Use
Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.
Kidneys (Image Source: parashospitals.com)
December 20, 2021 /BioValleyBIOON/ --BayerBayer recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending approval.Kerendia (finerenone), 10mg or 20mg), for adult patientsTreatment and Type 2Diabetes(Chronic Kidney Disease (CKD, Stage 3 and 4 with Proteinuria) Associated with Type 2 Diabetes (T2D)). Despite the availability of current treatment options, many CKD patients associated with T2D progress to renal failure or premature death. These patients urgently need treatment options that can delay the progression of kidney disease and reduce the risk of cardiovascular events.
Now, the CHMP opinion will be submitted to the European Commission (EC) for review, which typically makes a final decision within 2 months. If approved, Kerendia will become the first non-steroidal MR antagonist in Europe, offering a new treatment option for adult patients with T2D-related CKD to help improve renal outcomes.
Kerendia (finerenone) is a first-in-class, non-steroidal, selective mineralocorticoid receptor antagonist (MRA) that reduces the harmful effects of excessive mineralocorticoid receptor (MR) activation. Excessive MR activation can lead to inflammation and fibrosis, which are key drivers of CKD progression and cardiac damage.
In July 2021, Kerendia was approved through the priority review process.United StatesFDAApproved for the treatment of chronic kidney disease (CKD) with type 2DiabetesAdult patients with T2D, reducing the risk of sustained decline in estimated glomerular filtration rate (eGFR), end-stage kidney disease (ESKD), cardiovascular death, non-fatal myocardial infarction, and heart failure hospitalization. The drug is currently under regulatory review in the EU, China, and several other countries.
It is worth mentioning that,Kerendia is the first non-steroidal, selective MRA to demonstrate positive renal and cardiovascular outcomes in patients with CKD and T2D.Despite guideline-directed therapies, many patients with CKD and T2D still progress to kidney failure and remain at high risk for cardiovascular events.Kerendia's mechanism of action is different from existing therapies. By blocking the overactivation of MR, the drug directly targets inflammation and fibrosis to slow disease progression.
Finerenone Chemical Structure (Source: newdrugapprovals.org) and Mechanism of Action (Source: researchgate.net)
FDAThe approval of Kerendia, as well as the CHMP's positive recommendation for the approval of Kerendia, were both based on the positive results from the pivotal Phase 3 FIDELIO-DKD study. Relevant data were presented at the American Society of Nephrology (ASN) Kidney Week 2020 and published in October 2020 in the New England Journal of Medicine (NEJM). For more details, see:Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes。
The FIDELIO-DKD study was conducted in patients with CKD and T2D, evaluating the efficacy and safety of finerenone versus placebo. Patients in both groups received standard care, including glucose-lowering treatment and maximum tolerated doses of renin-angiotensin system (RAS) blockade therapy, such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs).
The results showed that the study met the primary endpoint:When combined with standard care, finerenone significantly reduced the composite primary endpoint risk of CKD progression, renal failure, and renal death compared to placebo.Specifically, with a median follow-up of 2.6 years, compared to placebo, finerenone significantly reduced the composite risk of first occurrence of kidney failure, a sustained decline in estimated glomerular filtration rate (eGFR) of ≥40% from baseline for at least 4 weeks, and renal death by 18% (HR=0.82; 95% CI: 0.73-0.93; p=0.0014). In pre-specified subgroups, the effect of finerenone on the primary outcome was generally consistent, and the treatment effect was sustained throughout the study period.
In addition, with a median follow-up of 2.6 years, compared with placebo,Finerenone also significantly reduced the risk of key secondary endpoints.: Cardiovascular death, non-fatal myocardial infarction, non-fatalStrokeThe composite risk of hospitalization for heart failure was reduced by 14% (relative risk reduction, HR=0.86 [95% CI: 0.75-0.99; p=0.0339]).
In this study, finerenone was well-tolerated, consistent with the safety profile observed in previous studies. The overall incidence of treatment-related adverse events and serious adverse events was similar between the two groups. Most adverse events were mild or moderate. The frequency of serious adverse events was lower in the finerenone group compared to the placebo group (31.9% vs 34.3%), while the incidence of hyperkalemia-related adverse events was higher (18.3% vs 9%). The occurrence of hyperkalemia-related serious adverse events was low in both groups (1.6% vs 0.4%), with no hyperkalemia-related deaths reported in either group. The proportion of patients discontinuing treatment due to hyperkalemia was 2.0% in the finerenone group versus 0.9% in the placebo group.
FIDELIO-DKD Clinical Data (Click the image to view a larger version)
Chronic Kidney Disease (CKD) isDiabetesOne of the most common complications, and an independent risk factor for cardiovascular disease. In all type 2DiabetesAmong patients, approximately 40% will progress to CKD. CKD is the leading cause of end-stage renal disease and kidney failure. In advanced stages, patients may require dialysis or a kidney transplant to sustain life.
Over a 10-year period, patients with type 2 diabetes and CKD are three times more likely to die from cardiovascular-related diseases compared to those with type 2 diabetes alone. It is well-known that in patients with type 2 diabetes and CKD, overactivation of the mineralocorticoid receptor triggers harmful processes (e.g., inflammation and fibrosis) in the kidneys and heart. Globally, CKD in patients with type 2 diabetes is the leading cause of renal failure.
Currently, the finerenone Phase III clinical program includes five Phase III studies (FIDELIO-DKD, FIGARO-DKD, FINEARTS-HF, FIND-CKD, FIONA). In treating CKD patients with T2D, two Phase III studies (FIDELIO-DKD, FIGARO-DKD) have been completed, enrolling 13,000 patients with a broad range of CKD severity from various regions globally, including those with early kidney damage and more advanced renal disease. These studies evaluated the effects of finerenone versus placebo, both combined with standard care, on renal and cardiovascular (CV) outcomes. (Bioon.com)