we can do better than binders
In the treatment of hyperphosphatemia in patients with chronic kidney disease (CKD) on dialysis,

Can We
Do Better
Than Binders?

Consistently achieving target phosphorus levels with phosphate binders is a difficult load for anyone to carry.

Binders were the best we could do for hyperphosphatemia management with the science we had.1

But with a deeper mechanistic understanding of phosphate absorption and the role of the paracellular pathway, Ardelyx is developing a new approach to advance patient care.

Watch a video of the
paracellular pathway in action
open messy binder
Most patients are unable to consistently achieve target phosphorus levels2
fishbane
Hear Dr. Glenn Chertow explain how we may
be underestimating the magnitude of the problem.

Phosphate binders are the only available class of medications approved for hyperphosphatemia1

In addition to low phosphorus diets and dialysis,
~80% of patients on dialysis are prescribed phosphate binders to manage hyperphosphatemia2
Despite the widespread use of phosphate binders, most patients on dialysis do not consistently achieve target phosphorus levels3,4
In any given month,
~42%
of phosphate binder–treated patients on dialysis have phosphorus >5.5 mg/dL3
Over a 6-month period,
~77%
of phosphate binder–treated patients on dialysis are unable to consistently maintain phosphorus levels ≤5.5 mg/dL4
Demonstrated in a chart audit including 1,015 patients on dialysis records submitted by 159 nephrologists.3
Evaluating the proportion of patients above target in a single month may underestimate the magnitude of the problem.

Hyperphosphatemia is an independent risk factor for the high rates of cardiovascular morbidity and mortality among patients with CKD on dialysis5-8

mortality risk graph serum phosphorus level
cardiovascular hospitalization graph serum phosphorus level
fishbane
Hear from Dr. Geoffrey Block about the
cardiovascular consequences of hyperphosphatemia

Clinical practice guidelines for lowering elevated phosphate levels

KDOQI logo
In patients with CKD stage 5 and those treated with dialysis, the KDOQI guidelines (2003) recommend that serum levels of phosphorus should be maintained between 3.5–5.5 mg/dL9
kdigo logo
In patients with CKD G3a–G5D, the KDIGO guidelines (2017) recommend lowering elevated phosphate levels toward the normal range (2.5–4.5 mg/dL)10,11
open messy binder

There are inherent limitations with the binding mechanism

fishbane
Hear from Dr. Steven Fishbane about challenges in the management of hyperphosphatemia

Phosphate binders have been the only available therapeutic approach for hyperphosphatemia since their introduction in the 1970s.1

MOA of Phosphate Binders12-16
small intestine with phosphate binder
As a class, phosphate binders:
  • Act by binding dietary phosphate to form insoluble complexes that pass through the GI tract12-16
  • Do NOT target or act on phosphate absorption pathways; they simply bind dietary phosphate in the GI tract12-16
Large pills12-16
Many pills (an average of 10.8 pills a day)17
Dosing with meals and snacks18
A difficult load for anyone to carry: Phosphate binders are the largest contributor to excessive pill burden for patients on dialysis.17,18
Despite our best efforts, the phosphate-binding mechanism has resulted in a treatment burden that can make consistent phosphate control feel impossible.20-22
In clinical trials with phosphate binders, between 14% and 27% of patients discontinued treatment due to adverse reactions13-16
Constipation is common in patients with CKD on dialysis and may be exacerbated by the constipation-inducing effects of phosphate binders19
A difficult load for anyone to carry: Phosphate binders are associated with a multitude of GI side effects.12-16
Despite our best efforts, the phosphate-binding mechanism has resulted in a treatment burden that can make consistent phosphate control feel impossible20-22
Man carrying multiple binders
The binding mechanism is to blame, not the patient
One of the biggest challenges for me was taking phosphorus binders. It’s a big deal. They’re gigantic, and were very difficult for me to swallow. I had to take 16–sometimes more–in a day. They’re also hard to remember.
– Derek, a patient living with kidney disease for almost
   30 years
derek patient perspective
See a patient’s perspective on
living with CKD on dialysis

Isn’t it time for a new approach that doesn’t rely on the mechanism of binding?

open messy binder

Our gut is telling us to look deeper into the science of phosphate absorption

Our gut is telling us to look deeper into the science of phosphate absorption

Sprague
Hear from Dr. Stuart Sprague about our new mechanistic understanding of phosphate absorption

The science behind
phosphate absorption

Mechanism of Phosphate Absorption
mechanism of phosphate absorption
Dietary phosphate absorption occurs via 2 distinct intestinal pathways23,24
  • 1
    Paracellular absorption occurs passively along concentration gradients through tight junction complexes between cell membranes23,24
  • 2
    Transcellular transport is active movement via carrier or transporter proteins through cell membranes23
Watch a video of the
paracellular pathway in action
We now know that paracellular absorption is the primary pathway by which phosphate absorption occurs. Targeting this pathway may be the key to mediating phosphate absorption in the GI tract23-25
  • Currently available dialysis regimens are not able to remove the excess phosphate successfully to achieve a neutral phosphate balance.4 Excess dietary phosphate creates a very large electrochemical gradient that drives phosphate absorption across the intestine24,25
  • The transcellular pathway has a limited capacity and rapidly becomes saturated25-27
  • In contrast, the paracellular pathway does not appear to saturate. The paracellular pathway is responsible for the bulk of phosphate absorption25-27
elderly couple happy and hugging

Patients are at the forefront of everything we do

Patients are at the forefront of everything we do

elderly couple happy and hugging

Ardelyx is committed to advancing the treatment of hyperphosphatemia in patients with CKD on dialysis

  • Treatments that target the paracellular pathway may be the key to achieving effective, consistent phosphorus control
  • Developing novel treatments that target the paracellular pathway may also lead to reductions in dosing frequency, pill size, and number of required pills

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