Ocedurenone (KBP-5074) Featured at ASN Kidney Week: Ocedurenone is a Potential New Treatment Option for Patients with Uncontrolled or Resistant Hypertension and Advanced CKD

Hepatic Impairment and Drug-Drug Interaction Study Results Presented

PRINCETON, N.J., Jan. 6, 2023 /PRNewswire/ -- KBP Biosciences PTE. Ltd. ("KBP Biosciences" or the "Company"), a clinical-stage biotechnology company dedicated to research, development, and commercialization of innovative medicines for the global market, today announced that an overview of Ocedurenone (KBP-5074) as a potential new treatment option addressing the unmet medical need of patients with uncontrolled and resistant hypertension and advanced CKD was presented by Pablo Pergola MD, PhD. Results of the hepatic impairment study and drug-drug Interaction study were presented as posters at ASN Kidney Week, November 4, 2022.

Pablo Pergola MD, PhD, Renal Associates PA, San Antonio, TX, presented an overview of Ocedurenone (KBP-5074). The title of Dr. Pergola's oral presentation was "Nonsteroidal Mineralocorticoid Receptor Blocker (KBP-5074) for Hypertension in Stage 4 CKD." Uncontrolled and resistant hypertension is a major contributor to the excess morbidity and mortality in patients with advanced kidney disease and presents an unmet medical need for new therapies. Dr. Pergola presented the BLOCK CKD Phase 2b trial (NCT03574363) efficacy and safety data for Ocedurenone. He provided a review of Ocedurenone properties that lead to clinically significant BP reduction and reduced risk of hyperkalemia in patients with resistant hypertension and advanced CKD. The ongoing Phase 3 study: CLARION CKD – Efficacy and Safety of KBP-5074 in Uncontrolled Hypertension with Moderate to Severe CKD (NCT04968184) was also presented. Dr. Pergola concluded that "Ocedurenone demonstrates potential as a new treatment option for high-risk patients who suffer from advanced chronic kidney disease and uncontrolled or resistant hypertension."

Dr. George Bakris MD, Director of the American Heart Association's Comprehensive Hypertension Center at the University of Chicago Medical Center and session moderator, was asked about the mechanism for BP lowering without significant hyperkalemia. "This is not like spironolactone. Ocedurenone is a non-steroidal MRA and is clearly different. It has different binding properties to the mineralocorticoid receptor with cofactors and gene activation, as well as other physiologic factors that lead to less hyperkalemia."

KBP also presented the Hepatic Impairment study and Drug-Drug Interaction study of Ocedurenone (KBP-5074), as posters, at the ASN Kidney Week Conference. The titles of the poster presentations are "Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist KBP-5074 in Individuals with Moderate Hepatic Impairment" and "Pharmacokinetics and Drug-Drug Interaction of KBP-5074 in Healthy Subjects". 

• In the hepatic impairment study (E-poster link 1), small decreases of area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C_max) upon systemic exposure to Ocedurenone (KBP-5074) in subjects with moderate hepatic impairment demonstrate low hepatic extraction and a dose adjustment does not appear to be warranted in patients with moderate hepatic impairment. Ocedurenone (KBP-5074) was safe and well tolerated in moderate hepatic impaired subjects.
  
  
• In the drug-drug interaction study (E-poster link 2), Ocedurenone (KBP-5074) was well tolerated when administered as a single 0.5-mg dose alone or in combination with itraconazole or rifampin. The study indicates that a strong Cytochrome P450 3A4 (CYP3A) inhibitor (itraconazole) has a weak effect on Ocedurenone pharmacokinetic properties, with less than 2-fold change in C_max and area under the curve time zero to time of last measurable concentration (AUC_last); whereas a strong CYP3A inducer (rifampin) has a strong effect on the pharmacokinetic properties of Ocedurenone, with about 5-fold decrease in AUC and terminal half-life (T_1/2).

"The data indicate that there may not be a need for dose adjustment in patients with moderate hepatic impairment and that ocedurenone is safe for use in this population. Co-administration with CYP3A4 inhibitors, commonly used in the target population, also appears to be safe," said James McCabe, MD, Deputy Chief Medical Officer.

"Data from these studies add to the growing body of evidence supporting the use of Ocedurenone in clinical medicine," said Julia Yang MD, Chief Operations Officer of KBP, "and provide a compelling rationale for the use of Ocedurenone (KBP-5074) for the treatment of patients with CKD."

In addition, KBP Biosciences presented results of a subgroup analysis of the Block-CKD Phase 2b clinical trial of Ocedurenone (KBP-5074) as a poster at the American Heart Association Scientific Sessions in Chicago November 5-7, 2022 (E-poster link 3). "The consistency of SBP reduction and safety data in more severe CKD patients with diabetes is highly informative. The analysis supports the robustness of data supporting the use of Ocedurenone regardless of CKD stage or diabetic status," said Bertram Pitt MD, University of Michigan.

"The data provide further justification for the use of Ocedurenone for the treatment of patients with advanced CKD and uncontrolled/resistant hypertension," said Fred Yang PhD, Chief Development Officer of KBP.

About KBP Biosciences

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 needs. KBP Biosciences' pipeline includes four novel drug candidates, two currently in clinical development covering multiple indications. CLARION-CKD, the Phase 3 clinical trial of Ocedurenone (KBP-5074), addressing the first indication of advanced CKD and uncontrolled hypertension, is being conducted globally.

About Ocedurenone (KBP-5074)

Ocedurenone (KBP-5074) is a non-steroidal MRA discovered and developed by KBP Biosciences. Ocedurenone (KBP-5074) selectively binds to recombinant human MRs with much higher affinity than to recombinant human glucocorticoid, progesterone, and androgen receptors which can produce antihypertensive, renal and cardioprotective effects. At present, the Phase 3 clinical trial of the first indication for Ocedurenone (KBP-5074), advanced CKD and uncontrolled hypertension, is underway. Other indications of Ocedurenone are planned, including CV risk reduction, CKD progression, heart failure, etc. Ocedurenone (KBP-5074) has been investigated in nine clinical studies including the BLOCK-CKD Phase 2b study. Ocedurenone (KBP-5074) is expected to provide a new treatment option addressing the unmet medical needs of patients with advanced CKD and uncontrolled hypertension.

Block-CKD was a randomized, double-blind, placebo-controlled, multi-center, Phase 2b study to assess the efficacy, safety, and PK of KBP-5074 0.25 mg QD and KBP-5074 0.5 mg QD versus placebo in subjects with moderate to severe CKD and uncontrolled hypertension and demonstrated significant blood pressure lowering with minimum risk of hyperkalemia. The subgroup analysis was conducted to evaluate safety (eGFR change and serum potassium levels) and efficacy (SBP reduction) of Ocedurenone in patients across different CKD stages, and with or w/o diabetes. Similar small dose-dependent increases in serum potassium were observed in nearly all subpopulations. Consistent and clinically meaningful SBP reduction at Day 84 was observed in the subgroups analyzed. These conclusions are being confirmed in a larger ongoing Phase 3 trial ("Clarion-CKD").

E-poster link 1: Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist Ocedurenone (KBP-5074) in Individuals with Moderate Hepatic Impairment:
https://kbpbio.com/docs/2022%20ASN%20Poster%20-%20%20KBP-5074%20PK%20in%20Individuals%20with%20Moderate%20Hepatic%20Impairment%20(final)%20.pdf

E-poster link 2: Pharmacokinetics and Drug-Drug Interaction of Ocedurenone (KBP-5074) in Healthy Subjects: 
https://kbpbio.com/docs/2022%20ASN%20Poster%20-%20Pharmacokinetics%20and%20Drug-Drug%20Interaction%20of%20KBP-5074%20in%20Healthy%20Subjects%20final.pdf

E-poster link 3: Effect of Ocedurenone (KBP-5074) in Patients with Uncontrolled Hypertension and Stage 3b/4 Chronic Kidney Disease - Subgroup Analysis of a Phase 2b Clinical Trial:
https://kbpbio.com/docs/2022%20AHA%20Poster%20-Effect%20of%20Ocedurenone%20in%20Patients%20with%20Uncontrolled%20Hypertension%20and%20Stage%203b4%20Chronic%20Kidney%20Disease%20-%20Subgroup%20Analys.pdf

For more information about KBP Biosciences, please visit the company website at https://www.kbpbiosciences.com/