Relypsa, Inc. today announced the start of dosing in a Phase 2b clinical trial of RLY5016 for the treatment of hyperkalemia in patients with diabetic nephropathy and chronic kidney disease (CKD). RLY5016 is a high capacity, non-absorbed, polymer-based potassium binder that is orally administered and has been shown to control serum potassium levels in previous studies. The trial, also known as AMETHYST-DN, will evaluate the safety and efficacy of RLY5016 in reducing high potassium levels (hyperkalemia) in patients who have moderate to severe kidney impairment (eGFR < 60 mL/min) and are being treated with renin-angiotensin-aldosterone-system (RAAS) inhibitors, including angiotensin receptor blockers (ARBs).
“With this study, we will make important advancements in our late stage RLY5016 development program”
"Effective potassium management with RLY5016 would give physicians the opportunity to treat hyperkalemia in high risk patients and remove serum potassium as an obstacle to appropriate RAAS inhibitor therapy," stated Mason Freeman, M.D., Professor of Medicine, Harvard Medical School, an expert in cardiovascular endocrinology who is heading up clinical strategy at Relypsa. "Maximum label doses of ARBs (losartan 100 mg/day and irbesartan 300 mg/day) are the only doses of this class of drugs that are proven to slow the progression of kidney disease and delay the onset of dialysis in hypertensive patients with diabetes and chronic kidney disease. Many physicians, however, use lower doses in order to lessen the hyperkalemia risk, despite outcome studies such as RENAAL, IDNT and IRMA2 not showing that lower doses of ARBs provide this renoprotective benefit," added Dr. Freeman.
The AMETHYST-DN trial is an open-label, international, multicenter study. The trial design includes an initial run-in period of up to four weeks, during which patients will be treated with proven, guideline-recommended doses of an ARB, and in some instances with both an ARB and an aldosterone antagonist (AA) as indicated for the subset of diabetic chronic kidney disease patients who also have uncontrolled hypertension. Instead of discontinuing or reducing the dose of RAAS inhibitor therapies per treatment guidelines when serum potassium becomes elevated, in the AMETHYST-DN study up to 300 patients with hyperkalemia will be randomized to RLY5016 in order to reduce serum potassium and enable patients to remain on proven doses of RAAS inhibitors.
The primary efficacy endpoint of the trial is mean reduction in serum potassium compared with baseline at four weeks. Secondary endpoints include mean reduction in blood pressure and proteinuria. Additionally, all patients completing eight weeks of treatment will have the option of continuing treatment for an additional 44 weeks, which will provide for a full year of safety monitoring.
"With this study, we will make important advancements in our late stage RLY5016 development program," stated Gerrit Klaerner, Ph.D., President of Relypsa. "We will focus on renal impaired, diabetic nephropathy patients who represent the population of greatest medical need and commercial interest, and generate one-year chronic exposure safety data, which is a rate limiting step to our NDA submission."