The FDA has approved Lokelma (sodium zirconium cyclosilicate), formerly ZS-9, for the treatment of adults with hyperkalemia,1 a serious condition characterised by elevated potassium levels in the blood associated with cardiovascular, renal and metabolic diseases.2
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.2,3 To help prevent the recurrence of hyperkalaemia, RAAS-inhibitor therapy is often modified or discontinued, which can compromise cardio-renal outcomes and increase the risk of death.3,4
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.1 The FDA approval is supported by data from three double-blind, placebo-controlled trials and two open-label trials, which showed that for patients receiving Lokelma the onset of action was at 1.0 hour and the median time to achieving normal potassium levels in the blood was 2.2 hours, with 92 percent of patients achieving normal potassium levels within 48 hours from baseline.1,8 The treatment effect was maintained for up to 12 months.1,5,6,7,8
Steven Fishbane, MD, Professor, Donald and Barbara Zucker School of Medicine at Hofstra Northwell, New York, 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.”
The European Commission granted marketing authorisation for Lokelma in the European Union on 22 March 2018.
References
1 AstraZeneca. Lokelma Prescribing Information. May 2018.
2 National Kidney Foundation. “Clinical Update on Hyperkalemia.” 2014. Accessed 8 May 2018. https://www.kidney.org/sites/default/files/02-10-6785_HBE_Hyperkalemia_Bulletin.pdf.
3 Kuijvenhoven MA, Haak EA, Gombert-Handoko KB, Crul M. Evaluation of the concurrent use of potassium-influencing drugs as risk factors for the development of hyperkalemia. Int J Clin Pharm. 2013 Dec;35(6):1099-104.
4 Epstein M, Reaven NL, Funk SE, McGaughey KJ, Oestreicher N, Knispel J. Evaluation of the treatment gap between clinical guidelines and the utilization of renin-angiotensin-aldosterone system inhibitors. Am J Manag Care. 2015 Sep;21(11 Suppl):S212-S220.
5 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.
6 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.
7 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.
8 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.
(Source: AstraZeneca)
Filed Under: Drug Discovery
