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Results of Pre-Specified Exploratory Analysis of Phase 3 OPAL-HK Study Evaluating Effects of Veltassa on Blood Pressure and Aldosterone Published in Kidney International

REDWOOD CITY, Calif., June 27, 2016 (GLOBE NEWSWIRE) -- Relypsa, Inc. (NASDAQ:RLYP), a biopharmaceutical company, today announced that results of a pre-specified exploratory analysis of the Phase 3 OPAL-HK trial of Veltassa® (patiromer) for oral suspension were published online by Kidney International, the journal of the International Society of Nephrology. The previously published OPAL-HK study evaluated Veltassa in patients with hyperkalemia (elevated blood potassium levels) and chronic kidney disease (CKD) who were taking renin angiotensin aldosterone system (RAAS) inhibitors. Results of this newly published analysis found that patients taking Veltassa in the study had significant decreases in systolic and diastolic blood pressure and reduced levels of aldosterone in the blood. Aldosterone is a hormone that plays an important role in the body’s regulation of blood pressure and blood potassium levels.

The publication is available in the Articles in Press section of the Kidney International website at http://www.kidney-international.org/article/S0085-2538(16)30186-7/fulltext.

“High aldosterone levels can be problematic for patients as they are associated with worsening of cardiovascular and kidney disease and are associated with increases in blood pressure,” said Matthew R. Weir, M.D., lead author of the Kidney International paper, lead investigator of the OPAL-HK trial, and professor and director of the Division of Nephrology at the University of Maryland School of Medicine in Baltimore. “This analysis suggests that patiromer’s potassium lowering effects may be associated with reductions in blood pressure and aldosterone production. These findings could be important for people with CKD and are worth evaluating further.”

Results of Pre-Specified Analysis of OPAL-HK Trial
The main results of the pivotal Phase 3 OPAL-HK study of Veltassa were previously published in the New England Journal of Medicine.1

This pre-specified exploratory analysis examined the effect of Veltassa on systolic and diastolic blood pressure, as well as various cardiovascular and renal biomarkers including: levels of aldosterone in the blood, plasma renin activity (PRA; a measure of the activity of the plasma enzyme, renin, which regulates angiotensin and aldosterone production), and urinary albumin-to-creatinine ratio (UACR; a test used to diagnose and monitor kidney disease by evaluating how much albumin is excreted in the urine). Results of this analysis are summarized below.

During the initial four-week treatment phase, when all patients were taking Veltassa:

  • Systolic blood pressure significantly decreased by -5.64 mmHg and diastolic blood pressure significantly decreased by -3.84 mmHg (p<0.0001 for both).
  • Mean levels of aldosterone in the blood significantly decreased by -1.99 ng/dL (p=0.0001).
  • PRA did not change.
  • UACR significantly decreased by -203.7 mg/g (p=0.0003).

Following the initial treatment phase, during the eight-week randomized placebo-controlled withdrawal phase:

  • Mean systolic blood pressure and diastolic blood pressure were significantly reduced in patients taking Veltassa (-6.70 mmHg; p<0.0001 and -2.15 mmHg; p≤0.05, respectively); in patients taking placebo, mean changes in systolic blood pressure and diastolic blood pressure were not significant (-1.21 mmHg and +1.72 mmHg, respectively).
  • Mean aldosterone levels were maintained at baseline levels in patients taking Veltassa (+0.23 ng/dL); in patients taking placebo, levels significantly increased (+2.78 ng/dL; p≤0.03).
  • There were no statistically significant changes in PRA in patients taking Veltassa; PRA significantly decreased in patients taking placebo (-3.90 µg/L/hr; p=0.0067).
  • By the end of the withdrawal phase, 94 percent of patients in the Veltassa group were still receiving their RAAS inhibitor medication, compared with 44 percent of patients in the placebo group. Among patients in the placebo group, 52 percent discontinued RAAS inhibitor therapy because their hyperkalemia was insufficiently controlled while taking these medications.

About OPAL-HK
The OPAL-HK trial evaluated 243 CKD patients with hyperkalemia (blood potassium levels ≥5.1 to <6.5 mEq/L). The primary endpoints were achieved and Veltassa was well tolerated. Mild-to-moderate constipation was the most common adverse event.

The trial had two phases. In the treatment phase, all patients received Veltassa and the primary endpoint was the mean change in the blood potassium level from baseline to week four. In the randomized withdrawal phase, patients who had moderate-to-severe hyperkalemia at baseline (potassium levels 5.5 to <6.5 mEq/L) and achieved target potassium levels (3.8 to <5.1 mEq/L) in the treatment phase, were randomly assigned to continue Veltassa or switch to placebo for another eight weeks. The primary endpoint in the randomized withdrawal phase was the difference between the Veltassa group and the placebo group in the median change in potassium levels over the first four weeks of that phase.

About Hyperkalemia
Approximately 3 million people in the United States with stage 3 or 4 CKD and/or heart failure have hyperkalemia, or elevated blood potassium levels. Hyperkalemia can cause abnormal heart rhythms and even sudden death. There are often no warning signs, meaning a person can unknowingly experience spikes in potassium levels recurrently and be at risk for these cardiac events. Some medicines that are frequently prescribed to people with CKD and heart failure to help delay progression of their underlying disease can cause hyperkalemia as a side effect. These include RAAS inhibitors such as ARBs (angiotensin receptor blockers), AAs (aldosterone antagonists) and ACE (angiotensin-converting-enzyme) inhibitors.

About Veltassa
Veltassa is a potassium binder approved for the treatment of hyperkalemia. Veltassa should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.

Made in powder form consisting of smooth, spherical beads, Veltassa is mixed with water (90 milliliters or 3 ounces) and taken once-a-day with food. Veltassa is not absorbed and acts within the gastrointestinal tract. It binds to potassium in exchange for calcium, primarily in the colon. The potassium is then excreted from the body through the normal excretion process.

IMPORTANT SAFETY INFORMATION

The Prescribing Information for Veltassa includes a Boxed Warning that Veltassa binds to many other orally administered medications, which could decrease their absorption and reduce their effectiveness. Other oral medications should be administered at least 6 hours before or 6 hours after Veltassa. Doctors should choose Veltassa or the other oral medication if adequate dosing separation is not possible.

Contraindications
Veltassa is contraindicated in patients with a history of a hypersensitivity reaction to Veltassa or any of its components.

Worsening of Gastrointestinal Motility
Use of Veltassa should be avoided in patients with severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders, because Veltassa may be ineffective and may worsen gastrointestinal conditions. Patients with a history of bowel obstruction or major gastrointestinal surgery, severe gastrointestinal disorders, or swallowing disorders were not included in clinical studies.

Hypomagnesemia
Veltassa binds to magnesium in the colon, which can lead to hypomagnesemia. In clinical studies, hypomagnesemia was reported as an adverse reaction in 5.3 percent of patients treated with Veltassa. Approximately 9 percent of patients in clinical trials developed hypomagnesemia with a serum magnesium value <1.4 mg/dL. Doctors should monitor serum magnesium and consider magnesium supplementation in patients who develop low serum magnesium levels.

Adverse Reactions
The most common adverse reactions (incidence ≥2 percent) were constipation, hypomagnesemia, diarrhea, nausea, abdominal discomfort and flatulence. Mild to moderate hypersensitivity reactions were reported in 0.3 percent of patients treated with Veltassa and included edema of the lips.

For additional Important Safety Information and Veltassa’s full Prescribing Information, please visit www.relypsa.com/veltassa/prescribing-information.

About Relypsa, Inc.
Relypsa, Inc. is a biopharmaceutical company focused on the discovery, development and commercialization of polymeric medicines for patients with conditions that are often overlooked and undertreated and can be addressed in the gastrointestinal tract. The Company’s first medicine, Veltassa® (patiromer) for oral suspension, was developed based on Relypsa’s rich legacy in polymer science. Veltassa is approved in the United States for the treatment of hyperkalemia. Veltassa has intellectual property protection until 2030 in the United States and 2029 in the European Union. 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 analysis suggesting that patiromer’s potassium lowering effect may be associated with reductions in blood pressure and aldosterone production and that the analysis could be important for people with CKD. 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 and commercialization process, including regulatory requirements, the timing of Relypsa’s regulatory filings, Relypsa’s substantial dependence on Veltassa, Relypsa’s commercialization plans and efforts and other matters that could affect the availability or commercial potential of Veltassa. 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, 2015 and its Quarterly Report on Form 10-Q for the quarterly period ended March 30, 2016.

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.

Contact:
Charlotte Arnold
Vice President, Corporate Communications and Investor Relations
650.421.9352
IR@relypsa.com


Source:Relypsa, Inc.