Tenapanor in Hyperphosphatemia Is Effective but Has Cost, Market Barriers

Hyperphosphatemia occurs when serum phosphate levels are elevated and the extra phosphate binds to calcium, causing calcifications that may lead to kidney stones and atherosclerosis. In 2023, tenapanor (Xphozah; Ardelyx) was approved by the FDA to treat hyperphosphatemia in dialysis patients as an add-on therapy for those who had an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy.¹ Tenapanor has a unique mechanism of action and low pill burden, but the drug usage is restricted by cost barriers and a competitive market.

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Some of the current hyperphosphatemia drug treatments include calcium acetate (Calphron; Nephro-Tech), sevelamer (Renvela; Sanofi), and sucroferric oxyhydroxide (Velphoro; Vifor Fresenius). Calcium acetate and sucroferric oxyhydroxide work by binding to dietary phosphate to form a complex that is excreted through the feces to decrease phosphorus concentrations.^2,3 Sevelamer also binds dietary phosphate while working to decrease the absorption of phosphorus.⁴ Through inhibition of sodium/hydrogen exchanger 3 (NHE3), tenapanor also decreases phosphorus absorption by reducing its permeability.⁵

In the AMPLIFY trial (NCT03824587), researchers compared the effectiveness of phosphate binders with a placebo against phosphate binders with tenapanor. Patients who were taking a combination therapy of tenapanor and a phosphate binder achieved a greater reduction in target phosphate (< 5.5 mg/dL) compared to those only using a placebo and phosphate binder.⁶ Tenapanor’s unique mechanism of action is an asset to patients who are not achieving target phosphorus goals on phosphate binders.

Despite tenapanor’s effectiveness, there are several other hyperphosphatemia treatments on the market that may have lower associated costs for patients who require combination therapy.

When compared to phosphate binders such as calcium acetate, sevelamer, or sucroferric oxyhydroxide, it is understandable why many health insurance plans choose not to include tenapanor as a formulary drug and steer prescribers to lower-cost alternatives. Non-formulary drugs are typically covered at a lower rate compared to formulary drugs by a health insurance plan and require a prior authorization. This means patients may have to pay a higher cost-sharing percentage to get the medication under their health plan. Alternatively, some patients may use coupon codes from online websites. For example, a simple online search shows that sevelamer carbonate 800 mg (90 tablets) and calcium acetate 667 mg (180 capsules) are approximately $50 each for a 30-day supply, without insurance, depending on the patient’s location and pharmacy.^7,8 With insurance, these medications may be available to the patient at no extra cost, as they are typically lower-tiered drugs on a health plan’s formulary.

However, it is expected that a generic medication will have a lower cost compared to brand-name medications. Sucroferric oxyhydroxide, a brand name-only phosphate binder, is available for about $1700 (90 tablets) for a 30-day supply.¹⁰ In contrast, tenapanor is available at about $3000 (60 tablets) for a 30-day supply.¹¹ The actual prices of these medications are approximate, as they depend on the patient’s location and pharmacy choice. Though approximate, it can be expected that tenapanor may be double the cost of sucroferric oxyhydroxide for patients without insurance. It is no surprise why both patients and providers may be willing to use lower-cost phosphate binders, like calcium acetate, when compared to tenapanor. However, there is a risk of hypercalcemia with calcium acetate. The adverse effect profiles of sevelamer, tenapanor, and sucroferric oxyhydroxide are similar, with possible incidences of diarrhea.

The main differences between the phosphate binders lie in the pill burden. The target population for tenapanor are patients with chronic kidney disease who require dialysis. The average number of prescribed medications in this patient population is at least 9 different drugs due to coexisting conditions such as type 2 diabetes and hypertension.⁸ Depending on the serum phosphorus levels, a patient may be taking 6 tablets of calcium acetate per day, whereas only 3 tablets per day of sevelamer and sucroferric oxyhydroxide are needed initially.^2-4 For a patient already taking 9 different medications, a prescriber may be reluctant to add on calcium acetate or sucroferric oxyhydroxide when there is a similar effective option like tenapanor with only 2 extra pills per day required. A lower pill burden has been shown to increase medication adherence and a patient’s quality of life.¹²

Does the lower pill burden warrant the cost of tenapanor? It depends. For some patients, particularly those struggling with complex medication regimens or poor adherence, the reduced pill burden may justify the higher expense by improving quality of life and helping achieve target phosphorus levels. For others, especially those who tolerate phosphate binders well and can manage higher pill counts, lower-cost alternatives may remain the preferred choice. Ultimately, the decision to use tenapanor should be individualized, weighing clinical effectiveness, patient adherence, insurance coverage, and out-of-pocket costs. As more real-world data emerge and market dynamics evolve, its role in hyperphosphatemia management may become clearer.

REFERENCES

1. FDA approves Xphozah (tenapanos), a first-in-class phosphate absorption inhibitor. News release. Ardelyx. October 17, 2023. Accessed August 15, 2025. https://ir.ardelyx.com/news-releases/news-release-details/fda-approves-xphozahr-tenapanor-first-class-phosphate-absorption

2. Phoslo gelcaps [prescribing information]. Fresenius Medical Care; March 2011. Accessed August 15, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021160s015lbl.pdf

3. Velphoro [prescribing information]. Fresenius Medical Care; April 2018. Accessed August 15, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/205109s006lbl.pdf

4. Renvela [prescribing information]. Genzyme Corp; November 2014. Accessed August 15, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022127s011lbl.pdf

5. Zphozah [prescribing information]. Ardelyx; October 2023. Accessed August 15, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/213931s000lbl.pdf

6. Pergola PE, Rosenbaum DP, Yang Y, Chertow GM. A randomized trial of tenapanor and phosphate binders as a dual-mechanism treatment for hyperphosphatemia in patients on maintenance dialysis (AMPLIFY). J Am Soc Nephrol. 2021;32(6):1465-1473. doi:10.1681/ASN.2020101398

7. Calcium Acetate. GoodRx. Accessed August 15, 2025. https://www.goodrx.com/calcium-acetate

8. Sevelamer Carbonate. GoodRx. Accessed August 15, 2025. https://www.goodrx.com/sevelamer-carbonate

9. Generic Renvela. GoodRx. Accessed August 15, 2025. https://www.goodrx.com/renvela

10. Velphoro. GoodRx. Accessed August 15, 2025. https://www.goodrx.com/velphoro

11. Xphozah. SingleCare. Accessed August 15, 2025. https://www.singlecare.com/prescription/xphozah

12. Oosting IJ, Colombihn JMT, Kaasenbrood L, et al. Polypharmacy in patients with CKD: a systematic review and meta-analysis. Kidney360. 2024;5(6):841-850. doi:10.34067/KID.000000000000447