REDWOOD CITY, Calif.--(BUSINESS WIRE)--Relypsa, Inc., a clinical-stage biopharmaceutical company, today in a late-breaker poster presentation at the ASN Kidney Week 2013 Annual Meeting in Atlanta, GA, presented additional data in support of the company’s earlier disclosure of statistically significant topline efficacy results in both Part A and Part B of its two-part pivotal Phase 3 clinical trial evaluating patiromer for the treatment of hyperkalemia. According to the poster’s authors, patiromer provided effective serum potassium control with a well-tolerated safety profile that may allow continuous management of serum potassium in hyperkalemic patients, including those with chronic kidney disease (CKD), heart failure and type 2 diabetes, on concurrent renin angiotensin aldosterone system (RAAS) inhibitor therapy.
The poster, # SA-PO1085 entitled, “A Two-Part Trial of Patiromer for the Treatment of Hyperkalemia in Chronic Kidney Disease Subjects on Renin Angiotensin Aldosterone System Inhibition,” was presented by lead author, Dr. Matthew Weir, Professor and Director, Division of Nephrology, University of Maryland School of Medicine, Baltimore, MD.
Results from Part A – The Patiromer Treatment Phase
The poster reiterated the topline primary and secondary efficacy results for Part A of the trial: the change from baseline to week 4 in serum potassium showed a statistically significant reduction of 1.01 mEq/L (p < 0.001) and 76% of subjects had a serum potassium in the target range of 3.8 to < 5.1 mEq/L at week 4, which was statistically significant (95% confidence interval: 70%, 81%).
Additional results provided supportive evidence for the safety and tolerability of patiromer with the most common adverse events being mild to moderate gastrointestinal symptoms (19% of subjects), with mild to moderate constipation reported the most frequently (10% of subjects). There were no reports of severe gastrointestinal events and all serious adverse events were assessed as not related to the study medication.
Results from Part B – The Placebo-Controlled Randomized Withdrawal Phase
The poster reiterated the topline efficacy results for Part B of the trial: after having treated hyperkalemia and controlled serum potassium in the treatment phase (Part A), hyperkalemia recurred at any time during Part B in significantly more placebo subjects than in patiromer subjects. For the Part B primary endpoint, the difference between the placebo and the patiromer groups in the median change from Part B baseline in serum potassium was 0.72 mEq/L (95% CI 0.46, 0.97), p < 0.001.
Safety results included in the poster for Part B demonstrated a similar proportion of placebo (46%) and patiromer (47%) subjects reported at least one adverse event. More subjects in the patiromer group (13%) reported gastrointestinal adverse events than in the placebo group (6%). There were no severe gastrointestinal adverse events reported in the patiromer group, with one severe gastrointestinal event reported in the placebo group. The frequency of other commonly reported adverse events in the patiromer group were either similar to, or less than, the placebo group. All serious adverse events were assessed as not related to the study medication.
According to Dr. Lance Berman, Chief Medical Officer of Relypsa, “We looked at the cumulative proportion of subjects in Part B who developed a recurrent hyperkalemic event, and we found that recurrent hyperkalemia occurred more frequently and earlier in the placebo group than in the patiromer group. What we learn from the Part B results is that ongoing chronic patiromer treatment is needed to maintain serum potassium levels in the normal range. If approved for the treatment of hyperkalemia, patiromer will offer physicians something they have not had before when caring for their patients – an effective and well tolerated medicine that can be used daily, over the long term, to treat and maintain control of hyperkalemia.”
Trial Background
The two-part Phase 3 clinical trial was conducted under an agreed upon special protocol assessment (SPA) with the U.S. Food and Drug Administration (FDA). Part A, in which all participants received patiromer, was a single-blind, single-arm trial in 243 subjects with hyperkalemia and CKD who were also being treated with RAAS inhibitor medications. The FDA-agreed upon primary endpoint of Part A under the SPA was the change in serum potassium from Part A baseline to Part A week 4. The secondary endpoint was the proportion of subjects with a serum potassium level in the target range of 3.8 to < 5.1 mEq/L at Part A Week 4.
- Part B, the placebo controlled randomized withdrawal part of the trial, was designed to provide additional evidence of the efficacy of patiromer in treating hyperkalemia and to assess the need for chronic dosing. Subjects from Part A whose baseline serum potassium level was greater than or equal to 5.5 mEq/L at enrollment and whose serum potassium level was controlled at week 4 were eligible for Part B. These subjects were then randomized into two groups; one to continue on patiromer, and a second to receive placebo for an additional eight weeks. The primary endpoint for Part B was the between group difference in the change in serum potassium from Part B baseline to week 4 of Part B or to an earlier time point when the subject first has serum potassium less than 3.8 mEq/L or greater than or equal to 5.5 mEq/L
About Hyperkalemia and Patiromer
Hyperkalemia, a life-threatening condition defined as abnormally elevated levels of potassium in the blood, is frequently prevalent in patients who suffer from renal impairment, hypertension, diabetes and/or heart failure. Hyperkalemia can lead to cardiac arrhythmia and sudden death. Patients with chronic kidney disease 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 the undesirable side effect of increasing serum potassium.
Patiromer (RLY5016 for Oral Suspension) is a high capacity non-absorbed oral potassium binder being developed for the treatment of hyperkalemia. Relypsa has completed several clinical trials of patiromer that have demonstrated the preliminary efficacy, safety and tolerability of patiromer in patients with hyperkalemia.
About Special Protocol Assessments
A Special Protocol Assessment is a written agreement between a sponsor and the FDA that the design and planned analysis of a clinical trial can adequately address objectives in support of a marketing application. Final determinations for marketing approval are made after a complete review of a marketing application. Approval is based on the entire data in the application. For further information regarding the SPA process, please visit the FDA website, www.fda.gov.
About Relypsa, Inc.
Relypsa, Inc. is a privately held clinical-stage 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 the treatment of hyperkalemia, a life-threatening condition defined as abnormally elevated levels of potassium in the blood, has been completed and the primary and secondary endpoints were met. Relypsa has global royalty-free commercialization rights to patiromer, which has intellectual property protection in the U.S. until at least 2030. More information is available at www.relypsa.com.
