Horizon Scanning Research May 2015 & Intelligence Centre Patiromer for hyperkalaemia – first line SUMMARY NIHR HSRIC ID: 6958 Patiromer is intended for the treatment of acute and/or chronic hyperkalaemia in patients with chronic kidney disease, type 2 diabetes or chronic heart failure. If licensed, patiromer will offer a novel treatment option This briefing is for hyperkalaemia in this patient group who currently have few well-tolerated based on effective therapies available. Patiromer is a non-absorbed cation-exchange information polymer that binds potassium predominantly in the lumen of the colon where available at the time potassium is the most abundant cation. Patiromer does not currently have of research and a Marketing Authorisation in the EU for any indication. limited literature search. It is not The incidence of hyperkalaemia varies between 1.1% and 10% of hospital intended to be a patients, of which 77% of cases are thought to be due to renal failure, 63% to definitive statement prescribed drugs, and 49% to hyperglycaemia. Hyperkalaemia is the reason for emergency haemodialysis in 24% of haemodialysis patients and accounts on the safety, for 3-5% of deaths in this patient group. In 2013-14, there were 7,214 efficacy or hospital admissions for hyperkalaemia in England, resulting in 20,725 bed effectiveness of the days and 9,942 finished consultant episodes. health technology covered and should There is limited good quality evidence on the role of drug treatment in not be used for hyperkalaemia. Aside from reducing potassium intake, treatment options commercial largely focus on reducing cardiac cell membrane excitability, shifting of purposes or potassium from the extracellular to the intracellular domain and reducing total commissioning body potassium. Patiromer has completed a phase III clinical trial comparing without additional its effect on serum potassium against treatment with placebo. information. This briefing presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health. NIHR Horizon Scanning Research & Intelligence Centre, University of Birmingham. Email: [email protected] m.ac.uk Web: www.hsric.nihr.ac.uk Horizon Scanning Research & Intelligence Centre TARGET GROUP • Hyperkalaemia: acute or chronic; in patients with chronic kidney disease not yet receiving dialysis, type 2 diabetes or heart failure – first line (in addition to intravenous treatment options in acute hyperkalaemia). TECHNOLOGY DESCRIPTION Patiromer (ILY-105, RLY5016) is a non-absorbed cation-exchange polymer that binds potassium predominantly in the lumen of the colon where potassium is the most abundant cation. This increases faecal potassium excretion, leading to removal of potassium from the body and lowering of serum potassium levels in patients with hyperkalaemia. Patiromer consists of uniformly sized spherical beads of a calcium salt formulated with a proprietary polymer, optimised to minimise gastrointestinal side effects and enhance palatability. Patiromer is intended for the treatment of acute and/or chronic hyperkalaemia in patients with chronic kidney disease (CKD) not yet receiving dialysis, type 2 diabetes or heart failure (HF). Patiromer is administered orally as a powder mixed with water. The proposed starting doses of patiromer are 8.4g or 16.8g, based on serum potassium level, taken once daily with food; doses may be titrated up or down as required. Patiromer does not currently have Marketing Authorisation in the EU for any indication. INNOVATION and/or ADVANTAGES If licensed, patiromer will offer a novel treatment option for hyperkalaemia in patients with CKD, diabetes or chronic HF, who currently have few well-tolerated effective therapies available. DEVELOPER Relypsa. AVAILABILITY, LAUNCH OR MARKETING In phase III clinical trials. PATIENT GROUP BACKGROUND An abnormally high serum potassium level is termed hyperkalaemia1. Extracellular potassium is tightly maintained between 3.5 and 5.0mmol/L by a complex system of potassium excretion and consumption2,3. Levels above 7mmol/L can cause significant haemodynamic and neurological consequences, while levels over 8mmol/L cause respiratory paralysis and cardiac arrest, which is rapidly fatal2. 2 Horizon Scanning Research & Intelligence Centre Hyperkalaemia can cause a rapid reduction in resting membrane potential which can lead to increased cardiac depolarisation and muscle excitability, which in turn leads to electrocardiographic (ECG) changes4. The risk of arrhythmias increases with levels of potassium greater than 6.5mmol/L; even small increases of potassium above this level can lead to rapid progression from peaked T waves on ECG to ventricular fibrillation or asystole4. Only two percent of total body potassium is found in the extracellular domain, while 95% of potassium is present in the intracellular domain3. In a 70kg male, this equates to about 59mmol/L of potassium in the extracellular domain3. On average, the daily intake of potassium through diet is about 70-100mmol/L5, but can be up to 200mmol/L, so the body removes extracellular potassium quickly to avoid hyperkalaemia3. Excretion of potassium takes place mainly via the kidneys, while about 5-10% is excreted in the digestive system and through sweat2,3. Hyperkalaemia is predominantly caused by kidney failure, drugs or disorders that inhibit the renin-angiotensin-aldosterone system, insulin deficiency or direct tissue trauma1,2,6; the majority of cases of hyperkalaemia are due to patients prescribed angiotensin converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) in conjunction with spironolactone with pre-existing or new renal impairment6. Most other cases occur because of potassium supplementation and prescription of potassium sparing drugs or diuretics6, such as trimethoprim, spironolactone and epleronone5. The condition can occur in both hospitalised patients and outpatients1. Symptoms of hyperkalaemia can include muscle weakness, fatigue, distal paraesthesia, respiratory depression and cardiac arrhythmias1,2. NHS or GOVERNMENT PRIORITY AREA This topic is relevant to: • NHS England. 2013/14 NHS Standard Contract for Ex-vivo Partial Nephrectomy Service (Adult). A06/S(HSS)b. • NHS England. 2013/14 NHS Standard Contract for Renal Dialysis: Hospital and Satellite (Adult). A06/S/a. • NHS England. 2013/14 NHS Standard Contract for Renal Dialysis: Home (Adult). A06/S/b. • NHS England. 2013/14 NHS Standard Contract for Renal Dialysis: Peritoneal (Adult). A06/S/c. • NHS England. 2013/14 NHS Standard Contract for Acute Kidney Injury (Adult). A06/S/d. • NHS England. 2013/14 NHS Standard Contract for Renal Assessment (Adult). A06/S/e. CLINICAL NEED and BURDEN OF DISEASE Hyperkalaemia usually occurs in patients with acute or chronic renal failure4. In 2011-12, the recorded prevalence of chronic kidney disease (CKD) among those aged 18 years and over was 4.3% in England; an estimated 1.9 million people7. However, the underlying prevalence of stage 3-5 CKD in England has been estimated at 6.8%, which equates to about three million adults7. The incidence of hyperkalaemia varies between 1.1% and 10% of hospital patients4,8, of which 77% of cases are thought to be due to renal failure, 63% to prescribed drugs, and 49% to hyperglycaemia, although in clinical practice there may be a combination of factors contributing to the disease4. Renin-angiotensin-aldosterone blocking drugs have been particularly implicated in the occurrence of hyperkalaemia; it may occur in as many as 10% of outpatients within a year of starting treatment, and is the underlying cause in 10-25%5 of patients admitted to hospital for hyperkalaemia4. Clinically significant hyperkalaemia is 3 Horizon Scanning Research & Intelligence Centre present in 5-10% of patients requiring regular haemodialysis (although this is more common when there is a long gap between dialysis)5 and has been reported in 10% of pre-dialysis samples in patients with end-stage renal disease4. Hyperkalaemia is the reason for emergency haemodialysis in 24% of haemodialysis patients and accounts for 3-5% of deaths in this patient group4. In 2013-14, there were 7,214 hospital admissions for hyperkalaemia (ICD-10 E87.5) in England, resulting in 20,725 bed days and 9,942 finished consultant episodes9. In 2013, there were 19 deaths registered, in England and Wales due to hyperkalaemia; 12 males and 7 females10. However, these numbers underestimate the size of the problem as many patients who are reported as dying from sudden unexpected cardiac death may have been affected by hyperkalaemia5. PATIENT PATHWAY RELEVANT GUIDANCE NICE Guidance • NICE clinical guideline. Chronic kidney disease: early identification and management of chronic kidney disease in adults in primary and secondary care (CG182). July 2014. • NICE clinical guideline. Intravenous fluid therapy in adults in hospital (CG174). December 2013. • NICE clinical guideline. Acute kidney injury: Prevention, detection and management of acute kidney injury up to the point of renal replacement therapy (CG169). August 2013. • NICE clinical guideline. Hypertension: Clinical management of primary hypertension in adults (CG127). August 2011. • NICE quality standard. Acute kidney injury (QS76). December 2014. • NICE quality standard. Renal replacement therapy services (QS72). November 2014. • NICE quality standard. Intravenous fluid therapy in adults in hospital (QS66).