Effective Date

Date of Origin 

07-01-2024            

07-01-2024

Xphozah®

(tenapanor)

tablet

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

1

Hyperphosphatemia

Hyperphosphatemia in chronic kidney disease (CKD) patients is a potentially life altering condition that can lead to cardiovascular calcification, metabolic bone disease (renal osteodystrophy) and the development of secondary hyperparathyroidism (SHPT). In clinical practice, the management of hyperphosphatemia is focused on controlling factors that are responsible for the intake and removal of phosphate from the body. There are three main strategies for correcting hyperphosphatemia: dietary restriction of phosphate intake, removing phosphate with adequate dialysis, and reducing intestinal absorption using phosphate binders. Reducing dietary phosphate intake can be challenging, as it is usually incompatible with the recommended daily protein intake, and diet control alone is insufficient. Currently available dialysis techniques are usually ineffective in normalizing phosphate concentration. Using phosphate binders to assist in the management of hyperphosphatemia in patients undergoing dialysis is common, with more than 95% of patients being prescribed phosphate binders.(2) Tenapanor is a first-in-class, minimally absorbed, small-molecule sodium-hydrogen exchanger 3 (NHE3) inhibitor with a unique mechanism of action that effectively reduces phosphate levels. Inhibition of gastrointestinal NHE3 results in increased sodium and water excretion as well as reduced paracellular permeability to phosphate. This modest intracellular proton retention generated is proposed to modulate tight junction proteins (claudins) resulting in increased transepithelial electrical resistance (TEER) and reducing permeability specific to phosphate, thereby decreasing phosphate absorption through the paracellular pathway.(4)

Efficacy

The ability of tenapanor to lower serum phosphorus in adults with CKD on dialysis was evaluated in 3 trials: TEN-02-201 [NCT02675998], TEN-02-301 [NCT03427125]), and TEN-02-202 [NCT03824587]). Both monotherapy trials (TEN-02-201 and TEN-02-301) enrolled patients who, following a 3-week washout period, had an increase in serum phosphorus of at least 1.5 mg/dL (compared to pre-wash out value) and a serum phosphorus level of at least 6.0 mg/dL and not more than 10.0 mg/dL.(1)

Study TEN-02-301 (PHREEDOM trial) was a 52-week phase 3 study. It included a 26-week randomized, active-controlled open-label treatment period, in which patients were randomized (3:1) to tenapanor 30 mg twice daily for 26 weeks (treatment period) or sevelamer carbonate (52-week safety period). Patients completing 26 weeks of treatment with tenapanor entered into a blinded placebo-controlled randomized withdrawal period and were rerandomized (1:1) to tenapanor or placebo for 12 weeks. These patients were eligible to enter the 14-week safety extension period. The primary efficacy end point was the difference in the change in serum phosphate from the end of the randomized treatment period to the end of the randomized withdrawal period, among participants who achieved a greater than or equal to 1.2 mg/dl decrease in serum phosphate during the randomized treatment period (efficacy analysis set). Efficacy was also evaluated in the intention-to-treat (ITT) analysis set. In the ITT analysis set, during the randomized withdrawal phase, the phosphorus concentration rose in the placebo group by 0.7 mg/dL (95% CI: (0.2, 1.1), p=0.002) relative to patients who remained on tenapanor. In the efficacy analysis set, the difference in estimated mean change in serum phosphate level between tenapanor and placebo from the beginning to the end of the randomized withdrawal period was −1.4 mg/dl (P<0.0001). Loosened stools were the most frequently reported adverse event.(1,3)

Study TEN-02-201 included an 8-week randomized, double-blind period that evaluated three dosing regimens of tenapanor (3 mg twice daily, 10 mg twice daily, or a titration regimen). This period was followed by a 4-week placebo-controlled randomized-withdrawal phase, during which patients were rerandomized 1:1 to their current tenapanor treatment or to placebo. During the randomized withdrawal phase, the phosphorus concentration rose in the placebo group by 0.7 mg/dL (95% CI: (0.3, 1.2), p=0.003) relative to patients who remained on tenapanor.(1) 

Study TEN-02-202 was a randomized, parallel-group, double-blind, placebo-controlled study that evaluated the effect of tenapanor on the change in serum phosphorus when used as add-on therapy in patients on stable phosphate-binder therapy with serum phosphorus greater than or equal to 5.5 mg/dL. During the 4-week period, the serum phosphorus decreased by 0.7 mg/dL (95% CI: (0.3, 1.0), p=0.0004) in the add-on tenapanor group as compared to the add-on placebo group.(1)

Safety

Xphozah has the following contraindications:(1)

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

1

Xphozah prescribing information. Ardelyx, Inc . October 2023.

2

Shaman AM, Kowalski SR. Hyperphosphatemia Management in Patients with Chronic Kidney Disease. Saudi Pharm J. 2016;24(4):494-505. doi:10.1016/j.jsps.2015.01.009.

3

Block, Geoffrey A., Bleyer, Anthony J., et al. Efficacy and Safety of Tenapanor for Long-term Serum Phosphate Control in Maintenance Dialysis: A 52-week Randomized Phase 3 Trial (PHREEDOM). Kidney 360.  2021; 2(10):1600-1610. doi: 10.34067/KID.0002002021.

4

Kovesdy, Csaba P., Adebowale, Adebiyi, et al. Novel Treatments from Inhibition of the intestinal Sodium-Hydrogen Exchanger 3. International Journal of Nephrology and Renovascular Disease.  2021; 14: 411-420. doi:  10.2147/IJNRD.S334024.

Xphozah

tenapanor hcl tab

20 MG ; 30 MG

M ; N ; O ; Y

N

Xphozah

tenapanor hcl tab

20 MG

60

Tablets

30

DAYS

Xphozah

tenapanor hcl tab

30 MG

60

Tablets

30

DAYS

Xphozah

tenapanor hcl tab

20 MG ; 30 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Xphozah

tenapanor hcl tab

30 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Xphozah

tenapanor hcl tab

20 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. ONE of the following:
   1. The requested agent is eligible for continuation of therapy AND ONE of the following:

1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
3. BOTH of the following:
   1. ONE of the following:
      1. The patient has a diagnosis of chronic kidney disease (CKD) AND ALL of the following: 
         1. The patient is on dialysis AND
         2. The patient has a phosphorus level of at least 5.5 mg/dL AND
         3. ONE of the following:
            1. ALL of the following:
               1. The patient has tried and had an inadequate response to at least ONE generic phosphate binder AND
               2. The patient will be using the requested agent in combination with phosphate binder therapy OR
            2. The patient is intolerant or has a hypersensitivity to generic phosphate binder therapy OR
            3. The patient has an FDA labeled contraindication to ALL generic phosphate binders OR
      2. The patient has another FDA labeled indication for the requested agent and route of administration AND
   2. If the patient has an FDA approved indication, then ONE of the following:
      1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
      2. There is support for using the requested agent for the patient’s age for the requested indication AND
4. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval:  6 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [NOTE: Patients not previously approved for the requested agent will require initial evaluation review] AND
2. The patient has had clinical benefit with the requested agent AND
3. ONE of the following:
   1. The patient is using the requested agent in combination with phosphate binder therapy OR
   2. The patient is intolerant or has a hypersensitivity to phosphate binder therapy OR
   3. The patient has an FDA labeled contraindication to ALL phosphate binders AND
4. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval:  12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR
2. ALL of the following:
   1. The requested quantity (dose) exceeds the program quantity limit AND
   2. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
   3. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR
3. ALL of the following:
   1. The requested quantity (dose) exceeds the program quantity limit AND
   2. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
   3. There is support for therapy with a higher dose for the requested indication

Length of Approval: Initial - up to 6 months; Renewal - up to 12 months