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The mechanism of action of XPHOZAH

Learn how XPHOZAH works to specifically block paracellular phosphate absorption.

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Transcript
00:07
Dietary phosphorus is absorbed primarily in the gastrointestinal tract via the paracellular pathway, the space between epithelial cells in the intestine, also known as tight junctions. These tight junctions are composed of proteins called claudins, which form the paracellular barriers and pores that determine tight junction permeability to various ions. Paracellular phosphate absorption is a passive process.
00:40
Phosphorus flows freely through the tight junctions down an electrochemical gradient without saturating. Phosphate absorption increases linearly with dietary phosphorus intake. While a significant amount of phosphate is absorbed each day in individuals with functioning kidneys, the majority of phosphate is then excreted in the urine, maintaining serum phosphorus concentrations within physiologic ranges. In patients with impaired kidney function, hyperphosphatemia develops when sustained intestinal phosphate absorption occurs without sufficient urinary phosphate excretion.
01:19
XPHOZAH is a first in class phosphate absorption inhibitor, PAI, that provides a non-binder mechanism of action. It is indicated to reduce serum phosphorus in adults with chronic kidney disease, CKD, on dialysis, as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy.
01:45
The different mechanism of action of XPHOZAH blocks the absorption of dietary phosphate through the paracellular pathway by inhibition of the sodium-hydrogen exchanger 3, or NHE3, in the GI tract. Without XPHOZAH, NHE3 facilitates the absorption of sodium in exchange for cellular protons. Local inhibition of NHE3 by XPHOZAH results in reduced sodium absorption, and consequently a modest proton retention within the intestinal cells.
02:20
This modest intracellular proton retention is proposed to induce a confirmational change in claudin proteins present in tight junctions, reducing permeability specific to phosphate. The decrease in dietary phosphate absorption through the paracellular pathway results in decreased serum phosphate levels. By blocking the absorption of dietary phosphorus through the paracellular pathway, the primary pathway of phosphate absorption, XPHOZAH provides a different mechanistic approach to the treatment of hyperphosphatemia.
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Indication

XPHOZAH (tenapanor) 30 mg BID is indicated to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy.

Important Safety Information

Contraindications

XPHOZAH is contraindicated in:

  • Pediatric patients under 6 years of age
  • Patients with known or suspected mechanical gastrointestinal obstruction

Warnings and precautions

Diarrhea

Patients may experience severe diarrhea. Treatment with XPHOZAH should be discontinued in patients who develop severe diarrhea.

Most Common Adverse Reactions

Diarrhea, which occurred in 43-53% of patients, was the only adverse reaction reported in at least 5% of XPHOZAH-treated patients with CKD on dialysis across trials. The majority of diarrhea events in XPHOZAH-treated patients were reported to be mild-to-moderate in severity and resolved over time, or with dose reduction. Diarrhea was typically reported soon after initiation but could occur at any time during treatment with XPHOZAH. Severe diarrhea was reported in 5% of XPHOZAH-treated patients in these trials.

For additional safety information, please see full Prescribing Information.

Indication

XPHOZAH (tenapanor) 30 mg BID is indicated to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy.

Important Safety Information

Contraindications

XPHOZAH is contraindicated in:

  • Pediatric patients under 6 years of age
  • Patients with known or suspected mechanical gastrointestinal obstruction

Warnings and precautions

Diarrhea

Patients may experience severe diarrhea. Treatment with XPHOZAH should be discontinued in patients who develop severe diarrhea.

Most Common Adverse Reactions

Diarrhea, which occurred in 43-53% of patients, was the only adverse reaction reported in at least 5% of XPHOZAH-treated patients with CKD on dialysis across trials. The majority of diarrhea events in XPHOZAH-treated patients were reported to be mild-to-moderate in severity and resolved over time, or with dose reduction. Diarrhea was typically reported soon after initiation but could occur at any time during treatment with XPHOZAH. Severe diarrhea was reported in 5% of XPHOZAH-treated patients in these trials.

For additional safety information, please see full Prescribing Information.

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