- Study to establish onset of action, conducted in diet-controlled patients with chronic kidney disease and moderate-to-severe hyperkalemia, taking RAAS inhibitor therapy
- Patiromer FOS significantly and rapidly decreased blood potassium levels within hours of the first administration and sustained the reduction around-the-clock for two treatment days and for 24 hours after the last dose
- Patiromer FOS was well tolerated with a safety profile consistent with that observed in other clinical trials
REDWOOD CITY, Calif., Sept. 16, 2015 (GLOBE NEWSWIRE) -- Relypsa Inc. (NASDAQ:RLYP), a biopharmaceutical company, today announced that results of its Phase 1 onset-of-action study of Patiromer for Oral Suspension (Patiromer FOS) were published in Kidney International, the journal of the International Society of Nephrology. Results showed that Patiromer FOS rapidly and significantly reduced blood potassium from baseline levels in patients with moderate-to-severe hyperkalemia (mean blood potassium levels at baseline: 5.93 mEq/L), who had chronic kidney disease (CKD) and were taking at least one renin angiotensin aldosterone system (RAAS) inhibitor. Patiromer FOS started to decrease potassium levels at 4 hours (the first evaluation time point) and the reduction became statistically significant at 7 hours (p=0.004). The reduction in blood potassium levels was significant at all following time points during the 48-hour treatment period (p≤0.004 for hours 7 and 10; p<0.001 for hours 12-48) and was sustained for 24 hours after the last dose. Patiromer FOS was well tolerated with a safety profile consistent with that observed in other clinical trials.
"This study demonstrated that Patiromer FOS induced a rapid, significant and sustained reduction in blood potassium levels in patients with hyperkalemia," said David A. Bushinsky, M.D., lead author of the paper, John. J. Kuiper Distinguished Professor of Medicine and of Pharmacology and Physiology at the University of Rochester School of Medicine, and Chief of the Nephrology Division at the University of Rochester Medical Center. "Consistent with previously published studies, we also observed that when patients stopped taking Patiromer FOS their blood potassium levels increased, providing further evidence of the medication's potassium-lowering effect and highlighting the need for chronic treatment."
"We designed this study to establish the onset of action of Patiromer FOS by evaluating patients with persistent moderate-to-severe hyperkalemia within a controlled environment, despite a low potassium and low sodium diet," said Lance Berman, M.D., chief medical officer of Relypsa. "The study is part of the comprehensive clinical trial program we submitted with our New Drug Application demonstrating the efficacy and safety of Patiromer FOS. If approved, we hope to bring Patiromer FOS to doctors and patients later this year."
The publication of the Phase 1 study can be accessed in the Advanced Online Publication section of the Kidney International website at http://www.nature.com/ki/journal/vaop/ncurrent/full/ki2015270a.html. The study was among eight clinical trials included in the New Drug Application submitted to the U.S. Food and Drug Administration (FDA) for Patiromer FOS. Also included were data from the Phase 3 OPAL-HK trial, which was conducted under a Special Protocol Assessment and published in the New England Journal of Medicine,1 and data from the 12-month Phase 2 AMETHYST-DN trial, which was published in the Journal of the American Medical Association.2 The FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of October 21, 2015.
Phase 1 Study Design and Results
The Phase 1 open-label, single-arm study evaluated the time to onset of the potassium-lowering action of Patiromer FOS in 25 CKD patients with moderate-to-severe hyperkalemia who were taking at least one RAAS inhibitor. It was conducted in inpatient clinical research units. Prior to starting treatment, patients were in the unit for 3 days on a strictly controlled low potassium and low sodium diet. Those with sustained hyperkalemia, despite the diet (baseline blood potassium levels >5.5 and <6.5 mEq/L), received 8.4 g of Patiromer FOS with morning and evening meals, a total of four doses over 48 hours, followed by a 7-day post-treatment follow-up period. The change from baseline in blood potassium levels was assessed at multiple time points during the 48-hour treatment period, including an initial assessment at 4 hours after the first dose and then every 2 to 4 hours.
- The mean baseline blood potassium level was 5.93 mEq/L.
- The study met its primary endpoint and showed a rapid and significant reduction in patients' blood potassium levels at 7 hours after the first dose of Patiromer FOS (p=0.004) and at every following time point during the 48-hour treatment period (p ≤0.004 for hours 7 and 10; p <0.001 for hours 12-48) and for 24 hours after the last dose.
- A decrease in potassium levels that was first observed at 4 hours, the first evaluation time point.
- At 48 hours (14 hours after the last dose), mean blood potassium had fallen by 0.75 mEq/L (p<0.001), and more than 90 percent of patients had values ≤5.5 mEq/L.
- Over the entire treatment period, mean blood potassium levels continued to decrease, with no increase before the next dose or for 24 hours after the last dose.
- A significant increase in mean blood potassium was observed 4 and 7 days after the last dose of Patiromer FOS.
- Patiromer FOS was well tolerated. All 25 patients completed the study and no serious or severe adverse events were reported. The most common adverse events were mild constipation (in two patients) and mild hypotension (in two patients). No hypokalemia (serum potassium <3.5 mEq/L) or hypomagnesemia (<1.4 mg/dL) were observed.
Hyperkalemia is a serious condition defined as abnormally elevated levels of potassium in the blood. It is frequently prevalent in patients who suffer from CKD, hypertension, diabetes and/or heart failure. Hyperkalemia can lead to life-threatening heart arrhythmias and sudden death. Patients with CKD or heart failure are at particular risk for developing hyperkalemia, especially those treated with RAAS inhibitors such as ARBs (Angiotensin Receptor Blockers), AAs (Aldosterone Antagonists), and ACE (Angiotensin-Converting-Enzyme) inhibitors. Although RAAS inhibition has been shown to protect kidney and cardiac function, many patients who could benefit from RAAS inhibitors are untreated or undertreated due to these medicines having an undesirable side effect of increasing blood potassium.
About Patiromer FOS
Patiromer FOS is a potassium binder, taken orally with a small amount of water, being developed for the treatment of hyperkalemia. Patiromer FOS has been evaluated in CKD patients with hyperkalemia, including a two-part Phase 3 program, a 12-month Phase 2 trial and a 48-hour Phase 1 onset-of-action trial. In all of those trials, Patiromer FOS met its efficacy endpoints and was well tolerated.
About Relypsa, Inc.
Relypsa, Inc. is a biopharmaceutical company focused on the development and commercialization of non-absorbed polymeric drugs to treat disorders in the areas of renal, cardiovascular and metabolic diseases. The company's lead product candidate is Patiromer for Oral Suspension for the treatment of hyperkalemia, a potentially life-threatening condition defined as abnormally elevated levels of potassium in the blood. A New Drug Application for Patiromer for Oral Suspension for the treatment of hyperkalemia was accepted by the U.S. Food and Drug Administration and is currently under review. Patiromer for Oral Suspension has intellectual property protection until 2030 in the United States and 2029 in the European Union. More information is available at www.relypsa.com.
To the extent that statements contained in this press release are not descriptions of historical facts regarding Relypsa, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including statements regarding the potential for, and timing of, approval and commercialization of Patiromer for Oral Suspension, or Patiromer FOS, and the potential Prescription Drug User Fee Act action date. Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development program, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the clinical drug development process, including the regulatory approval process, the timing of Relypsa's regulatory filings, Relypsa's substantial dependence on Patiromer FOS, Relypsa's commercialization plans and efforts and other matters that could affect the availability or commercial potential of Patiromer FOS. Relypsa undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of Relypsa in general, see Relypsa's current and future reports filed with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2014 and its Quarterly Report on Form 10-Q for the quarterly period ended June 30, 2015.
1 Weir MR, Bakris GL, Bushinsky DA, Mayo MR, Garza D, et al. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med. 2015; 372:211-221.
2 Bakris GL, Pitt B, Weir MR, Freeman MW, Mayo MR, et al. Effect of patiromer on serum potassium level in patients with hyperkalemia and diabetic kidney disease: The AMETHYST-DN Randomized Clinical Trial. JAMA. 2015;314(2):151-161.
CONTACT: Charlotte Arnold Vice President, Corporate Communications 650.421.9352 IR@relypsa.com