- Patiromer FOS significantly decreased blood potassium levels in patients with chronic kidney disease and hyperkalemia at four weeks (primary endpoint)
- Potassium levels were maintained at normal levels through 52 weeks of treatment
- Patiromer FOS was well tolerated when used chronically and the safety profile was consistent with that observed in other clinical trials
- Results of AMETHYST-DN trial of long-term use of Patiromer FOS were included in the New Drug Application (NDA) submitted to the U.S. Food and Drug Administration (FDA)
REDWOOD CITY, Calif., July 14, 2015 (GLOBE NEWSWIRE) -- Relypsa Inc. (NASDAQ:RLYP), a biopharmaceutical company, announced that one-year data from the Phase 2 AMETHYST-DN trial of Patiromer for Oral Suspension (Patiromer FOS) were published today in the Journal of the American Medical Association (JAMA). Results showed that patients with chronic kidney disease (CKD) and mild or moderate hyperkalemia who were treated with Patiromer FOS had statistically significant decreases in blood potassium levels from baseline at four weeks (p<0.001; primary endpoint). Patiromer FOS quickly reduced potassium levels, with significant reductions at the first post baseline assessment, approximately 48 hours after treatment started (p<0.001). Patients maintained normal blood potassium levels through 52 weeks of treatment. Patiromer FOS was well tolerated when taken for up to one year. All patients had CKD, type 2 diabetes and were taking renin-angiotensin-aldosterone-system (RAAS) inhibitors prior to and during study treatment.
"Hyperkalemia can be a life-threatening condition and there are currently no good options to treat it chronically, which is a very real concern for doctors with patients whose potassium levels are repeatedly elevated," said George Bakris, M.D., lead author of the JAMA paper, and professor of medicine and director of the Comprehensive Hypertension Center at the University of Chicago Medicine. "This study showed that Patiromer FOS was well tolerated, helped correct potassium levels quickly and maintained normal levels over a year of treatment in patients with chronic kidney disease."
"We've seen in clinical trials that when patients stopped taking Patiromer FOS, their potassium levels increased rapidly, demonstrating the need for chronic therapy to maintain control," said Lance Berman, M.D., chief medical officer of Relypsa. "We are excited by the results of the AMETHYST-DN trial which showed, for the first time, that an oral therapy could control potassium levels over the long-term. If approved, we hope to bring Patiromer FOS to doctors and patients later this year."
The data from this trial were previously presented by Dr. Bakris at the American Society of Nephrology (ASN) Annual Meeting in November 2014. The JAMA publication is available at http://jama.jamanetwork.com/article.aspx?articleid=2396477.
The AMETHYST-DN trial was among eight clinical trials included in the NDA submitted to the FDA for Patiromer FOS. Also included were data from a Phase 3 program, OPAL-HK, which was conducted under a Special Protocol Assessment and was previously published in the New England Journal of Medicinei. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of October 21, 2015.
AMETHYST-DN Trial Efficacy and Safety Results
AMETHYST-DN is a multi-center, randomized, open-label, dose-ranging Phase 2 clinical trial that included 306 patients with CKD stages 3 to 5, as well as type 2 diabetes. All patients were taking RAAS inhibitors to treat their CKD prior to and during study treatment and had mild-to-moderate hyperkalemia. Mild hyperkalemia was defined as potassium levels >5.0–5.5 mEq/L and moderate hyperkalemia as >5.5–<6.0 mEq/L. Study participants received one of three randomized total daily starting doses of Patiromer FOS: 8.4, 16.8 or 25.2 g for those with mild hyperkalemia, and 16.8, 25.2 or 33.6 g for those with moderate hyperkalemia.
The primary efficacy endpoint was mean change in potassium levels from baseline to week 4 and the primary safety endpoint was evaluation of adverse events through 52 weeks. Secondary endpoints included mean change in potassium levels from baseline at each monthly visit through 52 weeks.
Results showed that Patiromer FOS significantly reduced blood potassium levels across all dose groups in patients with mild or moderate hyperkalemia at week 4 and this effect was maintained through 52 weeks.
- Mild hyperkalemia patients: At week 4, blood potassium was reduced from baseline by a mean of 0.35 [0.22-0.48], 0.51 [0.38-0.64] and 0.55 [0.42-0.68] mEq/L for the 8.4, 16.8 and 25.2 g dose groups, respectively (p<0.001).
- Moderate hyperkalemia patients: At week 4, blood potassium was reduced from baseline by a mean of 0.87 [0.60-1.14], 0.97 [0.70-1.23] and 0.92 [0.67-1.17] mEq/L for the 16.8, 25.2 and 33.6 g dose groups (p<0.001).
- Through week 52, significant mean decreases in potassium from baseline at each monthly visit were observed (p<0.001) and the vast majority of patients with mild (83.1-92.7 percent) or moderate hyperkalemia (77.4-95.1 percent) had potassium levels within the target range (3.8-5.0 mEq/L).
- Significant reductions in mean potassium were seen at the first post-baseline assessment, approximately 48 hours after Patiromer FOS initiation, in both mild and moderate hyperkalemia patients (p<0.001).
- After discontinuing treatment with Patiromer FOS, significant increases in mean potassium levels were observed by day 3 in both patient groups (mild hyperkalemia: 0.25 [0.19-0.31] mEq/L; moderate hyperkalemia: 0.33 [0.20-0.46] mEq/L; p<0.001).
Over the 52 weeks of treatment, Patiromer FOS was well tolerated. The most common adverse events were worsening of CKD (9.2 percent), hypomagnesemia (an abnormally low blood level of magnesium; 8.6 percent), worsening of hypertension (7.9 percent), constipation (6.3 percent) and diarrhea (5.6 percent). No adverse events of worsening CKD were considered by investigators to be related to Patiromer FOS. The most common treatment-related side effects were hypomagnesemia (7.2 percent), constipation (4.6 percent) and diarrhea (2.7 percent). Throughout the 52 weeks, mean blood levels of magnesium remained within the normal range (1.5-2.4 mg/dL). No patients developed severe hypomagnesemia (<1.0 mg/dL), or had any serious adverse events (SAEs) or discontinued Patiromer FOS due to hypomagnesemia. Hypokalemia (lower than normal levels of potassium) occurred in 5.6 percent of patients. SAEs were reported for 44 patients (14.5 percent), none of which were attributed to Patiromer FOS by investigators. The most common SAE was worsening of CKD (2.0 percent).
About Hyperkalemia
Hyperkalemia, a serious condition defined as abnormally elevated levels of potassium in the blood, is frequently prevalent in patients who suffer from CKD, hypertension, diabetes and/or heart failure. Hyperkalemia can lead to life-threatening cardiac arrhythmia 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, which is 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. The pivotal clinical trial for Patiromer FOS was conducted under a Special Protocol Assessment with the FDA.
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 two-part pivotal Phase 3 trial of its lead product candidate, Patiromer for Oral Suspension, for the treatment of hyperkalemia, a potentially life-threatening condition defined as abnormally elevated levels of potassium in the blood, has been completed and the primary and secondary endpoints were met. 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. Relypsa has global royalty-free commercialization rights to Patiromer for Oral Suspension, which has intellectual property protection in the United States until at least 2030. More information is available at www.relypsa.com.
Forward Looking Statements
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 lack of, and need for, options to treat hyperkalemia chronically, the potential of Patiromer for Oral Suspension, or Patiromer FOS, to treat hyperkalemia chronically and the estimated timing of commercialization of Patiromer FOS. 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 March 31, 2015.
i 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.