In Phase IIIb DIALIZE trial, 41.2% of LOKELMA patients maintained
normal potassium levels pre-dialysis compared to 1% receiving placebo
WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca today presented positive results from the Phase IIIb DIALIZE
trial which investigated the efficacy and safety of LOKELMA (sodium
zirconium cyclosilicate) for the treatment of hyperkalemia in patients
with end-stage renal disease (ESRD) on hemodialysis.
Hyperkalemia is a serious condition characterized by elevated potassium
levels in the blood.
In the trial, 41.2% of patients with hyperkalemia on stable hemodialysis
receiving LOKELMA maintained pre-dialysis normal potassium levels (4-5
mmol/L) on at least three out of four dialysis treatments after the long
interdialytic interval and did not require urgent rescue therapy,
compared to 1.0% of patients receiving placebo. This was a statistically
significant (P<0.001) and clinically meaningful improvement.
The safety profile of LOKELMA observed in DIALIZE was consistent
with previous trials.
The results were presented as a late-breaking abstract at the 56th
European Renal Association – European Dialysis and Transplant
Association (ERA-EDTA) Congress in Budapest, Hungary and were published
in the Journal
of the American Society of Nephrology.
Elisabeth Björk, Senior Vice President, Head of Late-stage Development,
Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, said,
“These positive results show that LOKELMA can normalize potassium levels
in between dialysis sessions for patients with hyperkalemia who have
end-stage renal disease. There is a high unmet treatment need that
affects a large patient population and we believe LOKELMA can play a
critical role.”
Steven Fishbane, MD, Zucker School of Medicine at Hofstra/Northwell,
Great Neck, NY, and primary investigator in the DIALIZE trial, said, “An
estimated two million people worldwide have end-stage renal disease,
placing them at a higher risk for hyperkalemia. Despite being on
dialysis, many still have high potassium levels, which can be
life-threatening if left untreated. These results provide important
insights for the clinical community and patients, and have the potential
to transform the treatment paradigm.”
Hyperkalemia can be a result of cardiovascular, renal and metabolic
diseases, and use of certain medications such as
renin-angiotensin-aldosterone system (RAAS) inhibitors. Many patients
with ESRD have hyperkalemia despite being on hemodialysis. Prevalence
and severity of hyperkalemia is highest after the long interdialytic
interval, the longest number of days between dialysis sessions.
LOKELMA is a highly-selective, oral potassium-removing agent
currently approved and available in the US for the treatment of adults
with hyperkalemia. Data from the DIALIZE trial will support label
updates in the US as the dosing regimen used in the trial is not
currently approved.
INDICATION AND LIMITATION OF USE FOR LOKELMA™ (sodium zirconium
cyclosilicate) 10 g ORAL SUSPENSION
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
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 (HF) 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.
PLEASE
READ FULL PRESCRIBING INFORMATION For LOKELMA.
– ENDS –
NOTES TO EDITORS
About hyperkalemia
The risk of hyperkalemia is associated with common comorbidities
including chronic kidney disease (CKD), heart failure (HF) and diabetes,
and these are the same conditions in which renin-angiotensin-aldosterone
system (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 occurs in 23% to 47% of
patients with CKD and/or HF, with an estimated 200 million and 64
million people, respectively, living with each condition worldwide.
About DIALIZE
DIALIZE is the first ever randomized, placebo-controlled trial to
evaluate a potassium binder in patients on stable hemodialysis. The
Phase IIIb, multicenter, double-blind trial investigated the efficacy of
LOKELMA versus placebo in 196 patients on hemodialysis with
hyperkalemia. Patients were randomized to receive LOKELMA or
placebo once daily on non-dialysis days for a treatment period of 8
weeks. This included a 4 week dose adjustment phase (starting at 5 g and
titrated weekly in 5 g increments up to a maximum of 15 g) and a 4 week
evaluation phase on stable dose. The dosing regimen used in the DIALIZE
trial is not currently approved.
About LOKELMA
LOKELMA is an insoluble, non-absorbed sodium zirconium silicate,
formulated as a powder for oral suspension, that acts as a
highly-selective potassium-removing agent. It is administered orally, is
odorless, tasteless and stable at room temperature. It has been studied
in three double-blind, placebo-controlled trials, which included one
11-month open-label extension and in one separate 12-month open label
clinical trial in patients with hyperkalemia.
About AstraZeneca in Cardiovascular, Renal & Metabolism (CVRM)
CV, renal and metabolism together form one of AstraZeneca’s main therapy
areas and a key growth driver for the Company. By following the science
to understand more clearly the underlying links between the heart,
kidneys and pancreas, AstraZeneca is investing in a portfolio of
medicines to protect organs and improve outcomes by slowing disease
progression, reducing risks and tackling co-morbidities. Our ambition is
to modify or halt the natural course of CVRM diseases and potentially
regenerate organs and restore function, by continuing to deliver
transformative science that improves treatment practices and CV health
for millions of patients worldwide.
About AstraZeneca
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
therapy areas – Oncology, Cardiovascular, Renal & Metabolism and
Respiratory. AstraZeneca operates in over 100 countries and its
innovative medicines are used by millions of patients worldwide. For
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