COPPELL, TX, USA I January 13, 2014 I ZS Pharma, a specialty pharmaceutical company developing novel treatments for kidney, cardiovascular and liver disorders, today announced top-line results from the Extended Treatment Phase of ZS003, its pivotal Phase 3 trial of ZS-9. ZS-9 is a novel, investigational treatment for hyperkalemia. Top-line analyses of the safety and efficacy results showed that the trial met the pre-specified endpoint for the 12-day Extended Treatment Phase, demonstrating that both 5g and 10g of ZS-9 given once-daily maintained a statistically and clinically significant reduction in serum potassium (K+) relative to placebo. ZS-9 was also well-tolerated with a gastrointestinal (GI) adverse event rate and an overall adverse event rate similar to placebo across all doses tested.
Topline data from the Acute Phase of the ZS003 clinical trial was previously announced in a late-breaking clinical presentation on November 9, 2013 at the American Society of Nephrology’s Kidney Week. The trial also met the endpoint for the Acute Phase, demonstrating a rapid, statistically significant reduction in K+ over the initial 48 hours at doses of 2.5g, 5g and 10g administered three times daily. Taken together, the Acute Phase and Extended Treatment Phase results of the Phase 3 clinical trial support the safety and efficacy of ZS-9 in treating hyperkalemia and suggest that ZS-9 is safe, well-tolerated and can control hyperkalemia for extended periods.
“With chronic medical conditions such as chronic kidney disease, diabetes, and congestive heart failure on the rise, the incidence of this life-threatening condition is increasing, emphasizing the critical need for a new treatment that is rapid, predictable and safe,” said Geoffrey A. Block, M.D., Director of Clinical Research at Denver Nephrology, Associate Clinical Professor in Medicine at the University of Colorado Health Sciences Center, and a clinical investigator in the ZS003 trial. “It’s very encouraging that this Phase 3 trial met its endpoints in both the Acute and Extended Treatment Phases.”
ZS003 Phase 3 Trial Design
This randomized, double-blind, placebo-controlled pivotal Phase 3 clinical trial enrolled 753 patients with hyperkalemia (potassium levels 5-6.5 mEq/L), including patients with chronic kidney disease (CKD), heart failure, diabetes, and those on renin angiotensin aldosterone system (RAAS) inhibitor therapy.
For the Acute Phase, patients were randomized to receive one of four doses of ZS-9 (1.25g, 2.5g, 5g or 10g) or placebo, administered three times daily for the initial 48 hours. The primary endpoint of the clinical trial was the rate of change in serum K+ from baseline throughout the 48-hour dosing period. The trial met the primary endpoint at the 2.5g, 5g, and 10g doses. Patients whose serum potassium was normalized in the Acute Phase were then randomized to the Extended Treatment Phase.
In the Extended Treatment Phase, patients were randomized to one of four doses of ZS-9 (1.25g, 2.5g, 5g or 10g) or placebo administered once-daily for an additional 12 days. The endpoint of the Extended Treatment Phase of the clinical trial was the rate of change in serum K+ over the 12-day dosing period.
ZS003 Phase 3 Top-Line Results
Top-line results from the Extended Treatment Phase showed that ZS-9 was able to maintain a statistically significant reduction in serum potassium relative to placebo in patients over 12 days of once-daily dosing.
The trial met the Extended Treatment Phase endpoint at the 5g and 10g doses compared with placebo (P-values of 0.0075, and <0.0001, respectively).
ZS-9 was well-tolerated at all doses tested. Overall adverse event and GI adverse event rates and severities were comparable between the placebo and ZS-9 treated patients.
The Company plans to present full results from the Acute and Extended Treatment Phases of the Phase 3 clinical trial of ZS-9 at a medical meeting in 2014.
“The positive top-line results from both the Acute and Extended Treatment Phases of our Phase 3 clinical study are an important milestone for us as we work to bring ZS-9 to market to treat hyperkalemia in chronic and acute settings, regardless of the underlying cause of hyperkalemia,” said Robert Alexander, Ph.D., Chairman and CEO of ZS Pharma. “ZS-9 is a novel agent that is highly selective and has unique properties that may allow it to effectively, safely and rapidly remove excess potassium and maintain normal potassium levels. We are continuing to evaluate ZS-9 further in our late-stage clinical development program.”
About the ZS-9 Clinical Development Program
The ZS-9 clinical program is designed to investigate treatment of hyperkalemia associated with acute and chronic medical conditions. The Company plans to initiate an additional Phase 3 trial, the ZS004 trial, in early 2014. This randomized, double-blind, placebo-controlled trial is designed to confirm the optimal dose of ZS-9 for extended treatment using a month-long dosing period. Early in 2014, the Company also plans to initiate ZS005, an open label, safety trial that will demonstrate the safety and tolerability of ZS-9 in patients for at least one year of dosing. The Company plans to file a New Drug Application (NDA) to the United States Food and Drug Administration (FDA) by early 2015.
About Hyperkalemia
Hyperkalemia, or higher than normal potassium levels (typically defined as a serum potassium level >5 mEq/L), is a life-threatening metabolic condition that can lead to cardiac arrhythmia and sudden cardiac death. Hyperkalemia is characterized by abnormally high concentrations of potassium in the blood resulting from the inability of the kidneys to excrete potassium, impairment of mechanisms that transport potassium into cells, or a combination of both factors. The causes of hyperkalemia vary but the most common are chronic kidney disease (CKD), diabetes, congestive heart failure (CHF), hypertension and side effects from cardio-renal protective drug therapy, such as renin angiotensin aldosterone system (RAAS) inhibitors. In the United States, about 4 million patients with CKD, CHF and diabetes are estimated to have hyperkalemia.i ii iii The rise in these chronic underlying medical conditions and the lack of safe and efficacious treatment options underscores the need for a therapy for hyperkalemia that is safe, rapid and predictable, and offers a favorable side effect profile.
About ZS Pharma
ZS Pharma is a privately held specialty pharmaceutical company based in Coppell, Texas. ZS Pharma’s lead therapeutic candidate, ZS-9, is in Phase 3 clinical trials. It is being developed to treat hyperkalemia, a potentially life-threatening metabolic condition characterized by an abnormally high serum concentration of potassium. ZS Pharma is also pursuing the discovery of additional drug candidates that utilize its novel selective ion-trap technology for the treatment of kidney and liver diseases. Additional information is available at www.zspharma.com.
i Einhorn. Arch Internal Med. 2009 169:1156-1162.
ii Raebel MA. J Gen Int Med. 2010 April 25(4).
iii Desai A. Curr. Heart Fail. Rep. 2009,727-280 6.
SOURCE: ZS Pharma
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COPPELL, TX, USA I January 13, 2014 I ZS Pharma, a specialty pharmaceutical company developing novel treatments for kidney, cardiovascular and liver disorders, today announced top-line results from the Extended Treatment Phase of ZS003, its pivotal Phase 3 trial of ZS-9. ZS-9 is a novel, investigational treatment for hyperkalemia. Top-line analyses of the safety and efficacy results showed that the trial met the pre-specified endpoint for the 12-day Extended Treatment Phase, demonstrating that both 5g and 10g of ZS-9 given once-daily maintained a statistically and clinically significant reduction in serum potassium (K+) relative to placebo. ZS-9 was also well-tolerated with a gastrointestinal (GI) adverse event rate and an overall adverse event rate similar to placebo across all doses tested.
Topline data from the Acute Phase of the ZS003 clinical trial was previously announced in a late-breaking clinical presentation on November 9, 2013 at the American Society of Nephrology’s Kidney Week. The trial also met the endpoint for the Acute Phase, demonstrating a rapid, statistically significant reduction in K+ over the initial 48 hours at doses of 2.5g, 5g and 10g administered three times daily. Taken together, the Acute Phase and Extended Treatment Phase results of the Phase 3 clinical trial support the safety and efficacy of ZS-9 in treating hyperkalemia and suggest that ZS-9 is safe, well-tolerated and can control hyperkalemia for extended periods.
“With chronic medical conditions such as chronic kidney disease, diabetes, and congestive heart failure on the rise, the incidence of this life-threatening condition is increasing, emphasizing the critical need for a new treatment that is rapid, predictable and safe,” said Geoffrey A. Block, M.D., Director of Clinical Research at Denver Nephrology, Associate Clinical Professor in Medicine at the University of Colorado Health Sciences Center, and a clinical investigator in the ZS003 trial. “It’s very encouraging that this Phase 3 trial met its endpoints in both the Acute and Extended Treatment Phases.”
ZS003 Phase 3 Trial Design
This randomized, double-blind, placebo-controlled pivotal Phase 3 clinical trial enrolled 753 patients with hyperkalemia (potassium levels 5-6.5 mEq/L), including patients with chronic kidney disease (CKD), heart failure, diabetes, and those on renin angiotensin aldosterone system (RAAS) inhibitor therapy.
For the Acute Phase, patients were randomized to receive one of four doses of ZS-9 (1.25g, 2.5g, 5g or 10g) or placebo, administered three times daily for the initial 48 hours. The primary endpoint of the clinical trial was the rate of change in serum K+ from baseline throughout the 48-hour dosing period. The trial met the primary endpoint at the 2.5g, 5g, and 10g doses. Patients whose serum potassium was normalized in the Acute Phase were then randomized to the Extended Treatment Phase.
In the Extended Treatment Phase, patients were randomized to one of four doses of ZS-9 (1.25g, 2.5g, 5g or 10g) or placebo administered once-daily for an additional 12 days. The endpoint of the Extended Treatment Phase of the clinical trial was the rate of change in serum K+ over the 12-day dosing period.
ZS003 Phase 3 Top-Line Results
Top-line results from the Extended Treatment Phase showed that ZS-9 was able to maintain a statistically significant reduction in serum potassium relative to placebo in patients over 12 days of once-daily dosing.
The trial met the Extended Treatment Phase endpoint at the 5g and 10g doses compared with placebo (P-values of 0.0075, and <0.0001, respectively).
ZS-9 was well-tolerated at all doses tested. Overall adverse event and GI adverse event rates and severities were comparable between the placebo and ZS-9 treated patients.
The Company plans to present full results from the Acute and Extended Treatment Phases of the Phase 3 clinical trial of ZS-9 at a medical meeting in 2014.
“The positive top-line results from both the Acute and Extended Treatment Phases of our Phase 3 clinical study are an important milestone for us as we work to bring ZS-9 to market to treat hyperkalemia in chronic and acute settings, regardless of the underlying cause of hyperkalemia,” said Robert Alexander, Ph.D., Chairman and CEO of ZS Pharma. “ZS-9 is a novel agent that is highly selective and has unique properties that may allow it to effectively, safely and rapidly remove excess potassium and maintain normal potassium levels. We are continuing to evaluate ZS-9 further in our late-stage clinical development program.”
About the ZS-9 Clinical Development Program
The ZS-9 clinical program is designed to investigate treatment of hyperkalemia associated with acute and chronic medical conditions. The Company plans to initiate an additional Phase 3 trial, the ZS004 trial, in early 2014. This randomized, double-blind, placebo-controlled trial is designed to confirm the optimal dose of ZS-9 for extended treatment using a month-long dosing period. Early in 2014, the Company also plans to initiate ZS005, an open label, safety trial that will demonstrate the safety and tolerability of ZS-9 in patients for at least one year of dosing. The Company plans to file a New Drug Application (NDA) to the United States Food and Drug Administration (FDA) by early 2015.
About Hyperkalemia
Hyperkalemia, or higher than normal potassium levels (typically defined as a serum potassium level >5 mEq/L), is a life-threatening metabolic condition that can lead to cardiac arrhythmia and sudden cardiac death. Hyperkalemia is characterized by abnormally high concentrations of potassium in the blood resulting from the inability of the kidneys to excrete potassium, impairment of mechanisms that transport potassium into cells, or a combination of both factors. The causes of hyperkalemia vary but the most common are chronic kidney disease (CKD), diabetes, congestive heart failure (CHF), hypertension and side effects from cardio-renal protective drug therapy, such as renin angiotensin aldosterone system (RAAS) inhibitors. In the United States, about 4 million patients with CKD, CHF and diabetes are estimated to have hyperkalemia.i ii iii The rise in these chronic underlying medical conditions and the lack of safe and efficacious treatment options underscores the need for a therapy for hyperkalemia that is safe, rapid and predictable, and offers a favorable side effect profile.
About ZS Pharma
ZS Pharma is a privately held specialty pharmaceutical company based in Coppell, Texas. ZS Pharma’s lead therapeutic candidate, ZS-9, is in Phase 3 clinical trials. It is being developed to treat hyperkalemia, a potentially life-threatening metabolic condition characterized by an abnormally high serum concentration of potassium. ZS Pharma is also pursuing the discovery of additional drug candidates that utilize its novel selective ion-trap technology for the treatment of kidney and liver diseases. Additional information is available at www.zspharma.com.
i Einhorn. Arch Internal Med. 2009 169:1156-1162.
ii Raebel MA. J Gen Int Med. 2010 April 25(4).
iii Desai A. Curr. Heart Fail. Rep. 2009,727-280 6.
SOURCE: ZS Pharma
Post Views: 381
