KBP-5074, a highly-selective non-steroidal mineralocorticoid receptor antagonist, lowered clinic systolic blood pressure (SBP) by 10.2 mm Hg with reduced hyperkalemia risk in the phase 2b study
Article published online; to be included in July 2021 print edition of Hypertension (AHA)
PRINCETON, N.J., June 16, 2021 -- KBP Biosciences, a clinical-stage biotechnology company dedicated to research, development, and commercialization of innovative medicines for the global market, today announced publication of the results of the BLOCK-CKD (Blood Pressure in Chronic Kidney Disease) phase 2b study of KBP-5074 by the peer-reviewed AHA journal, Hypertension. BLOCK-CKD achieved its primary endpoint with clinical and statistical significance: systolic blood pressure (SBP) was reduced in both 0.5 mg and 0.25 mg KBP-5074 cohorts by −10.2 mm Hg and -7.0 mm Hg, respectively, compared to placebo. There were no reports of severe hyperkalemia or acute kidney injury with either dose of KBP-5074. The trial results of the BLOCK-CKD study paper were published online and will appear in the July 2021 print edition of the journal.
“Data from the BLOCK-CKD study demonstrate substantial systolic BP-lowering efficacy in a very difficult-to-treat hypertensive population with CKD,” said Dr. William B White, M.D., a professor of medicine from the Cardiology Center at the University of Connecticut School of Medicine who was not involved with the conduct of BLOCK-CKD. “While the steroidal MRAs, such as spironolactone and eplerenone are effective in lowering BP in the CKD patients, the risk of hyperkalemia is far too great to be used routinely in clinical practice,” said Dr. William B White. “The results of the BLOCK-CKD study show the potential for KBP-5074 to be a potentially best-in-class treatment option for patients with uncontrolled hypertension and advanced CKD, a major unmet medical need in a group of patients otherwise lacking a treatment option that is both safe and effective,” said Zhenhua Huang, Ph.D., Chairman of KBP Biosciences.
“Publication of the BLOCK-CKD Phase 2b trial results in such a prestigious peer-reviewed journal highlights the potential of KBP-5074 in advancing care in this patient population. Following consultation with the FDA, we are excited to move into a global Phase 3 program this year,” added Fred Yang, Ph.D., Chief Development Officer of KBP Biosciences and co-author of the manuscript. “These results further support the safety and efficacy of KBP-5074 for treating advanced CKD patients with uncontrolled hypertension,” said Dr. George Bakris, M.D., Director of the American Heart Association’s Comprehensive Hypertension Center at the University of Chicago Medical and co-lead investigator on the clinical trial, as well as lead author of the manuscript. “This publication highlights the importance and potential of KBP-5074 as a treatment option for patients with few, if any, options for treatment. I look forward to supporting the continuing development of KBP-5074 in a pivotal phase 3 trial study,” said Dr. Bertram Pitt, M.D., Professor Emeritus, University of Michigan Medical School and co-lead investigator of the BLOCK-CKD clinical trial.
About BLOCK-CKD
BLOCK-CKD was a phase 2b, international, multicenter, randomized, double-blind, placebo-controlled, parallel-group study that evaluated the safety, efficacy, and pharmacokinetics of the non-steroidal MRA KBP-5074 for uncontrolled hypertension in patients with stage 3b/4 CKD who were receiving background antihypertensive medication. 162 patients were randomized 1:1:1 to once-daily treatment with KBP-5074 0.25 mg, KBP-5074 0.5 mg, or placebo, stratified by estimated glomerular filtration rate (eGFR, ≥30 versus <30 mL/min/1.73 m2) and SBP (≥160 versus <160 mmHg). Male and female patients aged 18 through 85 years with stage 3b/4 CKD (eGFR ≥15 and ≤44 mL/min/1.73 m2) and uncontrolled Grade 1 and 2 systolic hypertension (resting trough cuff seated SBP ≥140 and ≤179 mm Hg) were enrolled. The primary efficacy endpoint was the change in trough cuff seated SBP from baseline to Day 84 of each dose of KBP-5074 compared to placebo. Secondary endpoints included diastolic blood pressure (DBP), changes in the urinary albumin-creatinine ratio (UACR), changes in serum potassium/incidence of hyperkalemia, and changes in eGFR and serum creatinine.
Approximately 40% of patients enrolled in the BLOCK-CKD study had eGFR in the range of ≥15 and ≤29 mL/min/1.73 m2, and approximately 90% of patients were taking at least three different antihypertensive medications. The study showed statistically significant reductions of SBP in patients with uncontrolled hypertension. The change in SBP from baseline to day 84 for patients in the 0.5 mg KBP-5074 cohort was −15.9 mm Hg relative to −5.3 mm Hg for the placebo cohort, a model adjusted mean reduction of -10.2 mm Hg (P=0.0026). For patients in the 0.25 mg KBP-5074 cohort, the change in SBP was −11.5 mm Hg compared to −5.3 mm Hg for the placebo cohort; a model adjusted mean reduction of -7.0 mm Hg (P=0.0399). Importantly, KBP-5074 was observed to be well-tolerated in advanced CKD patients, with no reported cases of severe hyperkalemia (potassium levels ≥6 mmol/L), acute kidney injury, or hospitalization due to hyperkalemia. This finding is especially important given that MRAs are typically contraindicated for patients with stage 3b/4 CKD. Further, KBP-5074 demonstrated clinically meaningful trends in the reduction of UACR and reduction in DBP from baseline to day 84.
About KBP-5074
KBP-5074 is a non-steroidal MRA discovered and developed by KBP Biosciences. KBP-5074 selectively binds to recombinant human MRs with much higher affinity than to recombinant human glucocorticoid, progesterone, and androgen receptors, suggesting that KBP-5074 should be effective in blocking the hypertensive and renal tissue damaging effects of aldosterone. KBP-5074 has been investigated in eight phase 1 studies and the BLOCK-CKD phase 2b study. Phase 3 study preparations are underway in close consultation with the FDA’s Division of Cardiology and Nephrology.
About Advanced CKD and Uncontrolled Hypertension
In the US alone, uncontrolled hypertension and stage 3b and 4 CKD afflicts more than 3 million patients in whom currently available MRAs are either contraindicated or must be used with extreme caution due to the risk of hyperkalemia. Treatments that lower blood pressure are available and include ACE-Is, ARBs, and diuretics, among others. Many patients with Stage 3B/4 CKD are at their maximum tolerated dose and still have uncontrolled or resistant hypertension. Available MRAs can provide additional blood pressure control in some of these patients, but usually not without the increased risk of hyperkalemia.
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