LOKELMATM Sodium Zirconium Cyclosilicate

SWIFT* K+ REDUCTION AFTER ONE HOUR.1,2
SUSTAINED K+ CONTROL FOR UP TO ONE YEAR
WHEN USED AS A MAINTENANCE THERAPY.†1
NOW IN YOUR HANDS.
New, highly-selective LOKELMA (sodium zirconium cyclosilicate)
is indicated for the treatment of hyperkalaemia in adult patients1

*In an emergency situation, standard of care should be used in line with local or national guidelines
Clinical trials with LOKELMA have not included exposure longer than one year

Clinical Studies

HARMONIZE Study Overview

HARMONIZE (ZS004), a Phase III, multicentre, multiphase, placebo-controlled study in 258 patients with hyperkalaemia. Open-label phase: LOKELMA 10 g three times daily, administered for 48 hours, at which time patients (n=237) with normokalaemia (3.5-5.0 mmol/L) were randomised to LOKELMA or placebo once daily, 5 g, 10 g, or 15 g, for 28 days.
Primary endpoint: mean serum K+ level with LOKELMA vs placebo on days 8-29. Eligible patients then continued treatment with LOKELMA 10 g once daily, which could be titrated to 5 g or 15 g, in an 11-month, open-label extension study (ZS004E). Please note that LOKELMA 15 g is not approved for use.1,2,23

LOKELMA HARMONIZE study overview1,2,23

HARMONIZE (ZS004) was a phase III, double-blind, randomised, multicentre trial (N=258) with extension phase (ZS004E)
HARMONIZE (ZS004) was a phase III, double-blind, randomised, multicentre trial (N=258) with extension phase (ZS004E)

* LOKELMA 15 g is not approved for use in the UK; 56 patients were randomised to 15 g maintenance therapy.
Patients enrolled in ZS004E received LOKELMA 10 g once daily, which could be titrated to LOKELMA 5 g once daily or LOKELMA 15 g once daily. Please note that the recommended starting dose for maintenance therapy with LOKELMA is
5 g once daily, which may be titrated to 10 g once daily as needed. No more than 10 g once daily should be used for maintenance therapy. The 5 g once daily dose can be down titrated to 5 g every other day.1,23

 

Primary endpoint

  • Comparison of mean serum K+ level on days 8–29 (ZS004)2
  • Maintenance of normokalaemia for 11 months (ZS004E)23

Secondary endpoints included

  • Proportion of patients who achieve and maintain normokalaemia2
  • Absolute and percentage change in serum K+ levels from baseline2

HARMONIZE Pivotal Trial

Swift serum K+ reduction as early as 1 hour with one dose*

In the 48-hour, open-label phase of the study:

  • One dose (10 g) of LOKELMA significantly reduced the mean serum K+ level after 1 hour (-0.2 mmol/L compared with baseline, 95% Cl, -0.3 to -0.2)*1,2
  • Median time to normokalaemia was 2.2 hours (interquartile range, 1.0–22.3)2
    • Mean baseline serum K+ was 5.6 mmol/L (standard deviation, 0.4 mmol/L)2
  • Typically, LOKELMA normalised K+ levels within 48 hours1,2 
    • 66% of patients achieved normokalaemia at 24 hours1
    • 88% of patients achieved normokalaemia at 48 hours1
  • Responses were greater in patients with more severe hyperkalaemia; serum K+ fell 0.8, 1.2 and 1.5 mmol/L
    at 48 hours in patients with baseline serum K+ <5.5, 5.5–5.9 and ≥6 mmol/L, respectively1,2

    *In an emergency situation, standard of care should be used in line with local or national guidelines

 

Mean serum K+ levels with LOKELMA 10 g three times daily for 48 hours (N=258)2

Graph of mean serum K+ levels with LOKELMA<sup>TM</sup> hyperkalaemia treatment
Graph of mean serum K+ levels with LOKELMA<sup>TM</sup> hyperkalaemia treatment

Adapted from Kosiborod M, et al. JAMA. 2014;312(21):2223-2233.

HARMONIZE Extension Phase

Sustained K+ control for up to 1 year when used as maintenance therapy*1

  • 88% patients in the extension phase, who were receiving LOKELMA, maintained an average
    serum K+ of 5.1 mmol/L over 11 months1

    *Clinical trials with LOKELMA have not included exposure longer than 1 year1

Mean serum K+ levels across correction, maintenance and extension phases†1

Mean serum K+ levels across correction, maintenance and extension phases
Mean serum K+ levels across correction, maintenance and extension phases

Adapted from Kosiborod M, et al. JAMA. 2014;312(21):2223-2233 and LOKELMA SmPC 2018.

Primary endpoint: mean serum K+ level with LOKELMA vs placebo on days 8–29. Eligible patients then continued treatment with LOKELMA 10 g once daily, which could be titrated to 5 g or 15 g, in an 11-month, open-label extension study (ZS004E). Please note that LOKELMA 15 g is not approved for use.1,2,23
Please note that the recommended starting dose for maintenance therapy with LOKELMA is 5 g once daily, which may be titrated to 10 g once daily as needed. No more than 10 g once daily should be used for maintenance therapy.
The 5 g once-daily dose can be down titrated to 5 g every other day.1

Significant reductions in mean serum K+ during days 8–29 was shown with LOKELMA vs placebo (p<0.001)2

  • 4.8 mmol/L with LOKELMA 5 g (95% CI, 4.6–4.9)
  • 4.5 mmol/L with LOKELMA 10 g (95% CI, 4.4–4.6)
  • 5.1 mmol/L with placebo (95% CI, 5.0–5.2)

HARMONIZE Across Patient Types

Consistent K+ response across patient types2

LOKELMA consistently reduced serum K+, regardless of comorbidities*, baseline K+ level or use of RAASi therapy2

The maintenance studies included patients with chronic kidney disease (58%), heart failure (10%), diabetes mellitus (62%) and RAASi therapy (68%)1

*CKD history, CKD eGFR, heart failure, diabetes mellitus, taking RAASi.

Mean serum K+ levels at 0 and 48 hours across baseline K+ levels.2

Mean serum K+ levels at 0 and 38 hours across baseline K+ levels
Mean serum K+ levels at 0 and 38 hours across baseline K+ levels

Adapted from Kosiborod M, et al. JAMA. 2014;312(21):2223-2233.2

005 Study Overview

ZS005 was an open-label, multicentre, multidose maintenance-dose titration trial to investigate the long-term safety
and efficacy of LOKELMA in patients with hyperkalaemia. Hyperkalaemic patients (n=751) with K+ levels of ≥5.1 mmol/L received LOKELMA for 24–72 h to achieve normokalaemia. Once in the normokalaemia range, patients were enrolled in the extended dosing phase and received 5 g of LOKELMA once daily. K+ levels were assessed throughout the first month and every 4 weeks thereafter through month 12. During the extension phase the dosages were adjusted based on K+,
with patients taking either 5 g, 10 g or 15 g once daily or 5 g every other day.*4

Primary endpoint4

  • Restoration and maintenance of normokalaemia (3.5–5.0 mmol/L)

Secondary endpoints4

  • Proportion of subjects with normokalaemia (3.5–5.5 mmol/L) months 3–12
  • Mean serum K+ values months 3–12, 6–9 and 9–12
  • Change (absolute and percent) from acute phase K+ values
  • Change (absolute and percent) from acute phase bicarbonate values
  • Proportion of subjects with normal bicarbonate

LOKELMA 005 study overview4

ZS005 was an open-label, multicentre, multidose maintenance-dose titration trial
ZS005 was an open-label, multicentre, multidose maintenance-dose titration trial

*LOKELMA 15 g is not approved for use in the UK.

005 Study

LOKELMA dosing

Titrating the maintenance dose of LOKELMA can provide well-tolerated control of hyperkalaemia using the lowest effective dose for up to 12 months vs baseline serum K+ levels.4

  • Serum K+ was reduced to normokalaemic range in 66.0% of patients at 24 hours and in 77.9% of patients
    at 72 hours after initiating LOKELMA 10 g 3-times daily vs baseline serum K+ levels4,24
  • Normokalaemia was maintained for 12 months in 88.4% of patients, using the lowest effective dose of LOKELMA*24
  • LOKELMA was generally well tolerated with no new safety findings in this long-term study24
  • The extended maintenance group contained a small proportion (11%) of patients who were maintained throughout with LOKELMA 15 g once daily*24

*15 g once daily is not a licensed dose for maintenance treatment per the SmPC.

Sustained serum K+ control for up to 1 year when used as maintenance therapy1,24

Mean serum K+ levels during correction, maintenance and extension phases
Mean serum K+ levels during correction, maintenance and extension phases

Adapted from Fishbane S, et al. American Society of Nephrology Kidney Week. 2017.24

Off-drug values collected 7 (±1) days after the last administration of LOKELMA.

  • Most patients (75.3%) achieve normokalaemia within 48 hours on LOKELMA 10 g 3-times daily, but those who
    do not may still respond within 72 hours vs baseline serum K+ levels4
  • Validated the long-term (up to 12 months) safety and efficacy profile of LOKELMA in patients with hyperkalaemia
    vs baseline serum K+ levels1
  • Showed the efficacy and safety of a titrated LOKELMA maintenance dosing regimen, starting at 5 g once daily*
    for up to 12 months vs baseline serum K+ levels4
  • Presented evidence that serum K+ increased vs baseline levels after LOKELMA was stopped, confirming the need for continued serum K+ control4