WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca (NYSE: AZN) today announced that the US Food and Drug Administration (FDA) has approved LOKELMATM (sodium zirconium cyclosilicate), formerly ZS-9, for the treatment of hyperkalemia in adults.3
Hyperkalemia is a serious condition characterized by high levels of potassium in the blood (greater than 5.0 mEq/L).1,2,4 The risk of hyperkalemia increases significantly for patients with chronic kidney disease (CKD) and for those who take common medications for heart failure (HF), such as renin-angiotensin-aldosterone system (RAAS) inhibitors, which can increase potassium in the blood. Currently, patients who experience hyperkalemia while taking guideline recommended RAAS-inhibitor therapy, often have their therapy modified or discontinued.5,6,7
Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “We are pleased by today’s FDA approval of LOKELMA as it enables us to help address a long-standing clinical need with a new medicine that offers rapid and sustained treatment for adults with hyperkalemia. The consequences of hyperkalemia can be very serious and it’s reassuring for treating physicians that LOKELMA has demonstrated lowering of potassium levels in patients with chronic kidney disease, heart failure, diabetes and those taking RAAS inhibitors.”
LOKELMA is a highly selective, oral potassium-removing agent.3 The FDA approval comes on the back of LOKELMA receiving authorization from the European Commission (EC) for the treatment of hyperkalemia in adult patients and it is supported by data from three double-blind, placebo-controlled trials and two open-label long-term trials.1,2,4,8,9
Data from one clinical trial showed that for patients receiving LOKELMA, the onset of action was at one hour, the median time to achieving normal potassium levels in the blood was 2.2 hours, and 92% of patients achieved normal potassium levels within 48 hours from baseline.3,4 LOKELMA should not be used as an emergency treatment for life-threatening hyperkalemia.3 LOKELMA was effective in lowering potassium levels in patients with CKD, HF, diabetes and those taking RAAS inhibitors.1 The most common adverse event was mild to moderate edema at 6% with the recommended dose of 10 g once daily (range of 4 - 16% with 5 -15 g daily).3
Steven Fishbane, MD, Professor, Donald and Barbara Zucker School of Medicine at Hofstra Northwell, New York, and lead investigator of the ZS 005 study said, “This FDA approval represents an exciting milestone, as it stands to deliver a rapid, effective and generally well-tolerated treatment option to patients suffering from hyperkalemia in the US.”
INDICATION AND LIMITATION OF USE
LOKELMA is indicated for the treatment of hyperkalemia in adults.
LOKELMA should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.
IMPORTANT SAFETY INFORMATION FOR LOKELMA™ (sodium zirconium cyclosilicate) 10 g ORAL SUSPENSION
WARNINGS AND PRECAUTIONS:
- Gastrointestinal Adverse Events in Patients with Motility Disorders: Avoid LOKELMA in patients with severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders. LOKELMA has not been studied in patients with these conditions and it may be ineffective and may worsen gastrointestinal conditions
- Edema: Each 5 g dose of LOKELMA contains approximately 400 mg of sodium. In clinical trials of LOKELMA, edema was generally mild to moderate in severity and was more commonly seen in patients treated with 15 g once daily. Monitor for signs of edema, particularly in patients who should restrict their sodium intake or are prone to fluid overload (eg, heart failure or renal disease). Advise patients to adjust dietary sodium, if appropriate. Increase the dose of diuretics as needed
ADVERSE REACTIONS: The most common adverse reaction with LOKELMA was mild to moderate edema. In placebo-controlled trials up to 28 days, edema was reported in 4.4%, 5.9%, 16.1% of patients treated with 5 g, 10 g and 15 g of LOKELMA once daily, respectively vs 2.4% of patients receiving placebo.
DRUG INTERACTIONS: LOKELMA can transiently increase gastric pH. In general, oral medications with pH-dependent solubility should be administered at least 2 hours before or 2 hours after LOKELMA. Spacing is not needed if it has been determined the concomitant medication does not exhibit pH-dependent solubility.
NOTES TO EDITORS
The risk of hyperkalemia is associated with common comorbidities including chronic kidney disease, heart failure and diabetes, and these are the same conditions in which RAAS- inhibitors are recommended in guidelines. To help prevent the recurrence of hyperkalemia, important guideline recommended RAAS-inhibitor therapy is often modified or discontinued. Hyperkalemia may affect 40 to 50% of patients with CKD, and up to 50% of chronic heart failure (CHF) patients on RAAS inhibitors.4,10,11
About LOKELMA (sodium zirconium cyclosilicate) For ORAL SUSPENSION
LOKELMA (formerly known as ZS-9) is an insoluble, non-absorbed sodium zirconium silicate and acts as a highly selective potassium-removing agent. It is administered orally as an odorless and tasteless powder reconstituted in water.12 Stability trials indicate that it is stable at room temperature.3 The FDA approval is supported by data from three double-blind, placebo-controlled trials 3 and two open-label long-term trials, with nearly 1,800 patients that have been treated with LOKELMA to date.
About AstraZeneca in Renal-Cardio
AstraZeneca’s Renal-Cardio team takes a patient-centric approach that follows the science to address the multiple risk factors associated with Renal-Cardio disease, including a key strategic focus on chronic kidney disease (CKD). By leveraging our expertise in cardiovascular disease, AstraZeneca can better understand the interplay of these conditions and CKD to advance our scientific leadership in the Renal-Cardio space. Through novel therapies and therapy combinations that target both the complications of CKD and the underlying mechanisms of CKD progression, we are building a portfolio to aggressively help prevent, treat, manage and modify this public health issue in the US and globally.
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.
1 Packham D, Rasmussen HS, Lavin P, et al. Sodium zirconium cyclosilicate in hyperkalemia. New Engl J Med. 2015; 372:222-31. doi: 10.1056/NEJMoa1411487.
2 Ash S, Bhupinder S, Lavin P, et al. A phase 2 study on the treatment of hyperkalemia in patients with chronic kidney disease suggests that the selective potassium trap, ZS-9, is safe and efficient. Kidney Int. 2015; 88, 404-411. doi:10.1038/ki.2014.382.
3 LOKELMA™ (sodium zirconium cyclosilicate) [prescribing information] AstraZeneca Pharmaceuticals LP, Wilmington, DE; 2018.
4 Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia. JAMA. 2014. doi:10.1001/jama.2014.15688.
5 National Kidney Foundation. “Best practices in managing hyperkalemia in chronic kidney disease.” 2016. Last accessed 17 May 2018. https://www.kidney.org/sites/default/files/02-10-7259%20Hyperkalemia%20Tool.pdf
6 Yancy CW, Jessup M, Bozkurt B, et al; in collaboration with American College of Chest Physicians, Heart Rhythm Society, and International Society for Heart and Lung Transplantation. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):1495-1539.
7 National Collaborating Centre for Chronic Conditions. Chronic kidney disease: national clinical guideline for early identification and management in adults in primary and secondary care. Royal Coll Phys. 2008:3-201.
8 U.S. National Institutes of Health. “Open-label Safety & Efficacy of ZS (Sodium Zirconium Cyclosilicate) 10g qd to Extend Study ZS004 in Hyperkalemia.” NCT02107092. 2016. Last Accessed 23 March 2017. https://clinicaltrials.gov/ct2/show/NCT02107092?term=zs&rank=1.
9 Fishbane S, Pergola PE, Packham DK, et al. Long-term efficacy and safety of sodium zirconium cyclosilicate for hyperkalemia: 12-month, open-label, phase 3 study. Poster presentation at: American Society of Nephrology Kidney Week 2017; November 2017; New Orleans, LA. Abstract #2759765.
10 Kovesdy CP. Management of hyperkalemia in chronic kidney disease. Nat Rev Nephrol. 2014. doi:10.1038/nrneph.2014.168
11 Vardeny O, et al. Incidence, predictors, and outcomes related to hypo- and hyperkalemia in patients with severe heart failure treated with a mineralocorticoid receptor antagonist. Circ HeartFail. 2014;7: 573–579.
12 Stavros F, Yang A, Leon A, et al. Characterization of structure and function of ZS-9, a K+ selective ion trap. PLoS One. 2014 Dec 22;9(12):e114686.
US-19717 Last Updated 5/18