CLINICAL TRIALS PROFILE FOR LOKELMA

All Clinical Trials for Lokelma

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT04063930 ↗	The Effect of Sodium Zirconium Cyclosilicate on Albuminuria in Patients With Type 2 Diabetes and Hyperkalemia	Recruiting	AstraZeneca	Phase 4	2019-10-01	To investigate whether concomitant treatment with Lokelma can improve the efficacy of standard blockade of the renin-angiotensin system in patients with type 2 diabetes, diabetic nephropathy and hyperkalemia.
NCT04063930 ↗	The Effect of Sodium Zirconium Cyclosilicate on Albuminuria in Patients With Type 2 Diabetes and Hyperkalemia	Recruiting	Zealand University Hospital	Phase 4	2019-10-01	To investigate whether concomitant treatment with Lokelma can improve the efficacy of standard blockade of the renin-angiotensin system in patients with type 2 diabetes, diabetic nephropathy and hyperkalemia.
NCT04063930 ↗	The Effect of Sodium Zirconium Cyclosilicate on Albuminuria in Patients With Type 2 Diabetes and Hyperkalemia	Recruiting	Steno Diabetes Center Copenhagen	Phase 4	2019-10-01	To investigate whether concomitant treatment with Lokelma can improve the efficacy of standard blockade of the renin-angiotensin system in patients with type 2 diabetes, diabetic nephropathy and hyperkalemia.
NCT04585542 ↗	Comparison of Potassium Binders in the ER	Recruiting	University of California, Irvine	Phase 4	2020-10-20	Compare efficacy of 3 oral potassium binders (cation exchange resins) on lowering blood potassium, in patients presenting to the Emergency Room with acute hyperkalemia.
NCT04789239 ↗	OPtimizing Aldosterone Receptor Antagonist Therapy by Sodium Zirconium Cyclosilicate in Heart Failure	Recruiting	AstraZeneca	Phase 2	2021-09-01	Mineralocorticoid receptor antagonists (MRA) is one of cornerstones in the treatment of heart failure with reduced ejection fraction (HFrEF). However, MRA has been extremely under-used globally. The main reason for this seems to be increased risk of hyperkalemia in individuals on MRA. Theoretically, by limiting the risk of hyperkalemia it could thus be possible to optimize MRA therapy. This is studied in this randomized controlled trial in which it is investigated whethere adding a potassium-binder in combination with MRA treatment prevent hyperkalemia to a greater extent than only using MRA. The specific aim of this study is to demonstrate the efficacy and safety of Sodium Zirconium Cyclosilicate (SZC) in optimizing MRA in symptomatic patients with HFrEF. A multicenter, randomized, placebo-controlled, double-blinded study in Sweden (n=230) The study consists of 2 phases: 1) open-label run-in within maximum 2 months, where all are treated with SZC to test tolarability, and 2) a 1:1 randomized, double-blinded and placebo-controlled treatment during 6 months. The open-label phase, in turn, consists of three periods: run-in (1 - 2 weeks), correc-tion (maximum 72 hours) and maintenance (at least 4 weeks) Sodium Zirconium Cyclosilicate (SZC) (Lokelma)®, 5 g, 10 g, orally, is an approved drug in Sweden. For correction of hyperkalemia, the recommended starting dose is 10 g, three times daily. Once normokalemia has been achieved, the maintenance reg-imen should be started with 5 g once daily. The dose can be titrated up to 10 g once daily or lowered to 5 g once every other day as needed, to maintain a normal level of potassium. Primary Objective: To demonstrate the efficacy of Sodium Zirconium Cyclosilicate (SZC) on optimiz-ing MRA in HFrEF, SZC vs Placebo. Primary Outcome Measure: Whether a patient maintains MRA at a dose ≥ 25 mg daily and S-K level in the normal range (3.5-5.0 mmol/L) at the end of study, without rescue therapy due to hyperkalemia at any point during the randomization phase.

Clinical Trial Conditions for Lokelma

Condition Name

Condition Name for Lokelma
Intervention	Trials
Hyperkalemia	4
Heart Failure	1
Heart Failure With Reduced Ejection Fraction	1
Hyperkalaemia	1

Condition MeSH

Condition MeSH for Lokelma
Intervention	Trials
Hyperkalemia	7
Renal Insufficiency, Chronic	2
Kidney Diseases	2
Heart Failure	2

Clinical Trial Locations for Lokelma

Trials by Country

Trials by Country for Lokelma
Location	Trials
United States	6
United Kingdom	3
Denmark	1
Germany	1
Spain	1

Trials by US State

Trials by US State for Lokelma
Location	Trials
California	2
North Carolina	1
Missouri	1
Indiana	1
Georgia	1

Clinical Trial Progress for Lokelma

Clinical Trial Phase

Clinical Trial Phase for Lokelma
Clinical Trial Phase	Trials
Phase 4	4
Phase 3	1
Phase 2	2

Clinical Trial Status

Clinical Trial Status for Lokelma
Clinical Trial Phase	Trials
Recruiting	5
Not yet recruiting	2

Clinical Trial Sponsors for Lokelma

Sponsor Name

Sponsor Name for Lokelma
Sponsor	Trials
AstraZeneca	4
Zealand University Hospital	1
Steno Diabetes Center Copenhagen	1

Sponsor Type

Sponsor Type for Lokelma
Sponsor	Trials
Other	8
Industry	4

Lokelma (Sodium Zirconium Cyclosilicate): Clinical Trials Update, Market Analysis, and Projections

Introduction to Lokelma

Lokelma, developed by AstraZeneca, is a highly selective, oral potassium-removing agent designed to manage hyperkalemia, a condition characterized by elevated potassium levels in the blood. This drug has been through a series of clinical trials and has gained regulatory approvals, but its journey has been marked by both successes and challenges.

Clinical Trials Update

FDA Approval and Initial Trials

Lokelma received FDA approval in 2018 after overcoming significant manufacturing hurdles that led to two previous rejections. The approval was based on data from five clinical trials, which demonstrated that Lokelma could lower abnormal potassium levels in the blood within an hour and restore normal levels within a median of 2.2 hours. These effects were maintained for up to a year with maintenance doses[2][4].

Recent Trial Developments

AstraZeneca has recently announced the discontinuation of two Phase III clinical trials, STABILIZE-CKD and DIALIZE-Outcomes, which were part of the CRYSTALIZE evidence program. These trials aimed to evaluate Lokelma's efficacy in managing hyperkalemia in patients with cardiac and renal diseases. The decision to halt these trials was due to substantially increased timelines for enrollment and reduced event rates, making it impractical to obtain trial data within a meaningful timeframe[1].

Clinical Trial Design and Outcomes

Trial 1 and Trial 2

The FDA approval of Lokelma was primarily based on two clinical trials. Trial 1 was a two-part, double-blind, randomized, placebo-controlled trial where patients received one of four doses of Lokelma or placebo for the initial 48 hours, followed by a maintenance phase. Trial 2 consisted of an open-label acute phase and a double-blind, randomized, placebo-controlled withdrawal phase. Both trials demonstrated Lokelma's efficacy in rapidly and consistently lowering potassium levels[4].

Key Findings

• Onset of Action: Lokelma showed an onset of action within 1 hour and achieved normal potassium levels within a median of 2.2 hours.
• Maintenance: The treatment effect was maintained for up to 12 months.
• Patient Demographics: The trials included a diverse population, with data on baseline demographics by sex and race[4].

Market Analysis

Market Size and Growth

The hyperkalemia treatment market is expected to grow significantly, with a projected CAGR of 16.79% from 2024 to 2029. North America, particularly the United States, is anticipated to hold a significant market share due to increasing healthcare expenditure, research and development, and the rising prevalence of hyperkalemia[5].

Market Share and Competition

Lokelma is expected to capture a substantial market share compared to its competitor, Veltassa (patiromer), due to its rapid onset of action, consistent efficacy, and favorable tolerability. Despite Veltassa's earlier market entry, Lokelma's stronger clinical profile is likely to drive its market dominance[2][3].

Regional Market Outlook

• North America: Expected to remain the largest market due to high healthcare expenditure and a growing prevalence of hyperkalemia.
• Asia-Pacific: Projected to be the fastest-growing region over the forecast period[5].

Challenges and Opportunities

Manufacturing and Regulatory Hurdles

Lokelma's journey to market was delayed by manufacturing issues, which allowed Veltassa to gain an early foothold. However, Lokelma's superior clinical profile and the lifting of the black-box warning on Veltassa have positioned it for significant market share[2].

Market Uptake and Patient Needs

The high burden of hyperkalemia, particularly in the aging population and those with comorbidities like kidney disease and heart failure, drives the demand for effective treatments. Lokelma's rapid action and long-term efficacy make it a preferred option for managing this condition[5].

Key Takeaways

• Clinical Trials: Lokelma has shown strong efficacy in clinical trials but faces recent challenges with the discontinuation of Phase III trials.
• Market Growth: The hyperkalemia treatment market is poised for significant growth, with Lokelma expected to capture a substantial market share.
• Regional Outlook: North America will remain a key market, while Asia-Pacific is expected to be the fastest-growing region.
• Competitive Advantage: Lokelma's rapid onset of action and consistent efficacy give it a competitive edge over other treatments.

FAQs

What is the current status of Lokelma's clinical trials?

Lokelma's Phase III clinical trials, STABILIZE-CKD and DIALIZE-Outcomes, have been discontinued due to enrollment and event rate issues.

How does Lokelma compare to Veltassa in terms of market share?

Lokelma is expected to capture a higher market share than Veltassa due to its rapid onset of action, consistent efficacy, and favorable tolerability.

What is the projected CAGR for the hyperkalemia treatment market?

The hyperkalemia treatment market is expected to grow at a CAGR of 16.79% from 2024 to 2029.

Which region is expected to be the fastest-growing in the hyperkalemia treatment market?

The Asia-Pacific region is projected to be the fastest-growing over the forecast period.

What are the key factors driving the growth of the hyperkalemia treatment market?

Increasing healthcare expenditure, rising prevalence of hyperkalemia, and advancements in research and development are key drivers of market growth.

Sources

1. AstraZeneca to halt Phase III hyperkalemia trials of Lokelma. Clinical Trials Arena, December 4, 2023.
2. AstraZeneca finally pushes potassium drug Lokelma to the FDA. FiercePharma, May 21, 2018.
3. Hyperkalemia- Market Insight, Epidemiology and Market Forecast. ASD Reports.
4. Drug Trials Snapshots: LOKELMA. FDA, August 20, 2020.
5. Hyperkalemia Treatment Market - Size, Share & Industry Analysis. Mordor Intelligence.