What Is patiromer?
Patiromer is a drug that works as a cation-exchanging polymer, meaning it binds to positively charged ions. It is taken orally and is not absorbed into the bloodstream from the gastrointestinal tract. Instead, patiromer, which contains a calcium-sorbitol complex, increases the removal of potassium from the body through fecal excretion. This action helps to lower high potassium levels in the blood.
Patiromer has been approved by the European Medicines Agency (EMA) for the treatment of hyperkalemia in adults. It is also being investigated in clinical trials for conditions such as hypertension, chronic kidney diseases, kidney transplant, end stage renal disease, and heart failure.
Uses and Conditions Under Study
Patiromer is primarily studied for the treatment of hyperkalemia, a condition characterized by dangerously high levels of potassium in the blood. Hyperkalemia can be a serious, life-threatening complication, particularly in patients with kidney disease or those undergoing dialysis. Patiromer helps by binding excess potassium in the digestive tract, preventing its absorption and increasing its excretion. A total of 18 trials have investigated patiromer for hyperkalemia or hyperkalaemia.
The drug is also being investigated for various kidney-related conditions, which often lead to hyperkalemia due to the kidneys' inability to properly excrete potassium. These conditions include Chronic Kidney Diseases, Kidney Transplant, End Stage Renal Disease, ESRD, and End Stage Renal Failure on Dialysis. Patiromer aims to help manage potassium levels in these vulnerable patient populations. There are 8 trials exploring patiromer in these kidney-related conditions.
Additionally, patiromer is being studied in patients with heart conditions, specifically Heart Failure and Heart Failure, Congestive. Patients with heart failure can be at risk for hyperkalemia, sometimes due to their underlying condition or medications they may be taking. Patiromer may offer a way to manage potassium levels in these individuals. A total of 3 trials are examining patiromer for heart failure.
Patiromer is also under investigation for Hypertension in 2 trials.
Dosing
Patiromer is available as an oral powder for suspension. Patients typically mix the powder from a packet with water, apple juice, or cranberry juice before administration. It is generally taken once daily. To avoid potential interference with the absorption of other oral medications, patiromer should be taken at least 3 hours apart from other oral medicinal products.
Various strengths of patiromer have been studied in clinical trials. These include daily doses of 8.4 g, 16.8 g, 25.2 g, and 33.6 g. The initial dose may be adjusted based on the patient's serum potassium levels. While typically given once daily, in some study cohorts, the total daily dose might be split depending on the dose and the participant's age.
Side Effects
In clinical trials, the most common side effect reported with patiromer was hypokalaemia (low potassium levels), which occurred in 15.0% of patients taking the drug compared to 10.7% of patients on placebo. Other common side effects included:
- Constipation: 5.3% of patients on patiromer experienced this, compared to 0.9% on placebo.
- Diarrhea: 4.8% of patients on patiromer, compared to 3.8% on placebo.
- Hypotension (low blood pressure): 4.1% of patients on patiromer, compared to 3.2% on placebo.
- Decreased glomerular filtration rate (a measure of kidney function): 3.4% of patients on patiromer, compared to 2.3% on placebo.
- Renal impairment: 3.1% of patients on patiromer, compared to 2.9% on placebo.
- Anemia: 2.5% of patients on patiromer, compared to 1.1% on placebo.
Some events were less common in patients taking patiromer compared to placebo. For example, hyperkalaemia (high potassium levels) occurred in 34.8% of patients taking patiromer versus 42.8% on placebo, reflecting the drug's intended effect. Hypomagnesaemia (low magnesium levels) was reported in 4.3% of patients on patiromer compared to 5.0% on placebo, and headache in 2.5% versus 4.1% on placebo.
Clinical Trial Results
Clinical trials have evaluated patiromer in various patient populations, primarily focusing on its ability to manage hyperkalemia (high potassium levels).
Heart Failure Patients
In a 28-day study (NCT00868439) involving heart failure patients, patiromer demonstrated a reduction in serum potassium levels by an average of 0.21 mEq/L, while patients on placebo experienced an increase of 0.23 mEq/L. Patients taking patiromer were significantly less likely to experience high potassium levels (above 5.5 mEq/L) during the treatment period, with only 7.3% compared to 24.5% on placebo. No patients discontinued the study due to elevated potassium levels on patiromer, whereas 6.1% of those on placebo did. Furthermore, 90.9% of patients on patiromer were able to have their spironolactone dose increased, compared to 73.5% on placebo.
Another study (NCT01130597) in heart failure patients with chronic kidney disease showed that patiromer reduced serum potassium by an average of 0.13 mEq/L by the end of treatment. A high proportion of patients, 90.5%, achieved serum potassium levels within the target range of 3.5 to 5.5 mEq/L at the end of treatment. All participants (100%) in this study were able to have their spironolactone dose increased up to 50 mg/day.
Patients with Hyperkalemia, Hypertension, and Diabetic Nephropathy
The AMETHYST-DN study (NCT01371747) investigated patiromer in patients with hypertension and diabetic nephropathy. Over 8 weeks, patiromer significantly reduced serum potassium levels, with reductions ranging from 0.35 to 0.54 mEq/L in patients with mild hyperkalemia (Stratum 1) and 0.88 to 0.95 mEq/L in those with moderate hyperkalemia (Stratum 2), depending on the starting dose. These reductions were sustained over a 52-week maintenance period, with mean reductions ranging from 0.44 to 1.17 mEq/L. At Week 8, a high percentage of participants achieved target potassium levels (3.5 to 5.5 mEq/L), ranging from 98.4% to 100% in Stratum 1 and 91.7% to 95.8% in Stratum 2.
General Hyperkalemia Treatment
The OPAL study (NCT01810939) for hyperkalemia patients showed that patiromer reduced serum potassium by an average of 1.01 mEq/L after 4 weeks of treatment. In a subsequent phase, patients who continued patiromer maintained their potassium levels, while those switched to placebo experienced a median increase of 0.72 mEq/L. Only 15% of patients on patiromer had severe hyperkalemia (serum potassium ≥ 5.5 mEq/L) compared to 60% on placebo.
Hemodialysis Patients
In an open-label study (NCT02033317) involving participants on hemodialysis, patiromer reduced serum potassium by an average of 0.23 mmol/L over 8 days.
Currently Recruiting Trials
Several clinical trials are currently seeking participants to further understand the benefits of patiromer, a medication used to manage high potassium levels. These studies aim to explore how patiromer can improve patient outcomes across different conditions and age groups.
One ongoing study, NCT06858280, sponsored by the Mario Negri Institute for Pharmacological Research, is a Phase 3 trial investigating patiromer in patients with hyperkalaemia and chronic kidney disease stages 3 and 4 who are also on chronic dialysis. This study aims to determine if patiromer, compared to a placebo, allows patients to reduce or eliminate dietary potassium restrictions without increasing their potassium levels. The trial is designed to enroll 40 participants.
For younger patients, Vifor Pharma, Inc. is sponsoring NCT05766839, a Phase 2 study focusing on children under 12 years of age with hyperkalaemia. This trial will evaluate the pharmacodynamic effects, safety, and tolerability of patiromer in this pediatric population, with an enrollment target of 32 children.
Additionally, the University Medical Center Groningen is conducting NCT06256991, a Phase 4 trial. This study explores whether patiromer can help patients with chronic kidney disease stage 3b/4, hyperkalemia, and hypertension better tolerate and increase the dosage of RAAS-blocker treatments. This placebo-controlled, double-blinded cross-over trial plans to enroll 44 participants.
Where to Participate
Clinical trials for patiromer are currently being conducted across the United States, with research sites located in 10 states. In total, there are 13 sites across 12 cities working to advance the understanding of patiromer.
Top participating locations include:
- Durham, North Carolina (2 sites)
- Jacksonville, Florida
- Miami, Florida
- Orlando, Florida
- Augusta, Georgia
- Peoria, Illinois
- Boston, Massachusetts
- Kansas City, Missouri
- Philadelphia, Pennsylvania
- Nashville, Tennessee
Eligibility criteria for some of these studies generally include participants aged 0 to 18 years, and all genders are welcome. These trials are specifically designed for patients with certain medical conditions and are not open to healthy volunteers.
Development Timeline
The journey to develop patiromer began in March 2009 with its first clinical trial. Since then, the medication has been the subject of 25 trials, involving a total of 3,345 participants, to explore its potential benefits across various conditions.
Early development was significantly driven by sponsors such as Relypsa, Inc. and Vifor Pharma, Inc., alongside numerous academic institutions and other pharmaceutical companies. Initially, research focused on conditions like IBS-C and hyperphosphatemia. Over time, the pipeline expanded considerably to address a broader range of indications, particularly hyperkalaemia, chronic kidney diseases, and related complications such as heart failure and kidney transplant.
The development program has progressed through all clinical phases, with 10 trials reaching Phase 4, indicating post-market surveillance or further investigation into approved uses. Additionally, nine trials were conducted in Phase 2, and five in Phase 3, demonstrating a thorough and extensive research effort to understand patiromer's efficacy and safety.