EMJ Nephrology interviewed two World-renowned experts in nephrology and cardiology, George Bakris and Faiez Zannad, regarding the challenges of treating uncontrolled hypertension (uHTN) in patients with advanced chronic kidney disease (CKD), a large unmet need for safe, effective therapies, and the potential of one therapy, Ocedurenone, to address this need.
Original article: EMJ-8.1-2023-1.pdf (emg-health.com)
Large Unmet Need
Patients with advanced CKD have a high burden of disease, compounded by serious comorbidities, most commonly hypertension. Controlling hypertension is vital in these patients to reduce the associated risks of morbidity and mortality, as well as reducing cardiorenal risk, but treatment options are limited due to safety concerns with the use of existing agents.
Bakris: “The PATHWAY-2 trial showed that in people with resistant hypertension without advanced CKD, spironolactone produced a greater reduction in blood pressure than a β-blocker and an α-blocker. However, it presents safety risks to patients when administered.”
“Then there is eplerenone, given twice a day, while safe, has a much weaker effect on blood pressure reduction than spironolactone. That’s all we’ve got, so that’s what people use.”
Dr Bakris also mentioned two existing nonsteroidal MRAs, esaxerenone which is “approved exclusively in Japan, for which there are no placebo-controlled comparisons”, and Finerenone which “ reduces blood pressure (placebo subtracted) variously from 3 mmHg (ARTS-DN, FIGARO-DKD, and FIDELIO-DKD studies) to approximately 8 mmHg (subset analysis from ARTS-DN study, eGFR of approximately 68, though office blood pressure from the same study showed around 3 mmHg reduction)”.
Future Option - Ocedurenone
Bakris: “Now, Ocedurenone, a non-steroidal MRA, shows clear promise in patients whose standard of care includes two, three, or more drugs. Ocedurenone is the only drug that has consistently steadied resistant hypertension in people with advanced CKD.”
In the first dedicated study of patients with uncontrolled hypertension and advanced CKD (BLOCK-CKD), Ocedurenone demonstrated efficacy in lowering blood pressure, together with a favorable safety profile. The experts were optimistic that it could provide a much-needed treatment option for these patients, with the added potential for reduction in the risk of cardiorenal outcomes.
“This study showed that Ocedurenone reduces SBP by 11 mmHg (placebo-subtracted), a reduction that could lead to potential approval. No other agent to date has steadied blood pressure as well in this group of patients. And the point is that these are the patients who need the most help.”
Zannad reinforced the importance of the hyperkalemia data for the clinical safety of Ocedurenone: “With Ocedurenone, we may for the first time have an MRA that is both safe and efficacious."
Bakris added: “A Phase 3 study (CLARION-CKD) of Ocedurenone in a similar patient population is ongoing. I remain optimistic that the signal seen in the BLOCK-CKD study will be seen in this larger study.”
“I remain excited about Ocedurenone. Its tolerability and efficacy in lowering blood pressure in a very high-risk group will have a significant impact on morbidity.”
“Mineralocorticoid receptors are so ubiquitous which may allow for indications beyond CKD and cardiovascular conditions. This is likely just the beginning for Ocedurenone.”
About Ocedurenone (KBP-5074)
KBP Biosciences is a global, clinical-stage biotechnology company, headquartered in Princeton, NJ, focused on discovering, developing, and commercializing innovative small-molecule therapeutics for the treatment of serious cardiorenal and infectious diseases with large unmet medical needs.
Ocedurenone (KBP-5074) is a non-steroidal MRA discovered and developed by KBP Biosciences. At present, the Phase 3 clinical trial of the first indication for Ocedurenone, advanced CKD and uncontrolled hypertension, is underway.
For more information about KBP Biosciences, please visit the company website at https://www.kbpbiosciences.com/