November 16, 2022
I am Dr. Ealena Callender, Senior Fellow at The National Center for Health Research (NCHR). Our think tank conducts, analyzes, and scrutinizes research on a range of health issues with particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.
Elevated phosphorus is a serious complication encountered by the majority of patients with chronic kidney disease on dialysis. Tenapanor represents a novel approach to this major problem. Still, we are concerned about this product because the data do not show it to be more effective than current options, and the significant side effects may lead to poor patient compliance.
This new drug is intended for a patient population subject to significant inequities. In the United States, end-stage renal disease (ESRD) disproportionately affects Black men and women. While Black Americans represent about 13% of the country’s population, they comprise more than 30% of patients with ESRD in the U.S.1. Blacks are nearly four times more likely to progress from early chronic kidney disease to ESRD than non-Hispanic Whites2. Also, hyperphosphatemia and its related adverse outcomes are more common in Blacks than Whites2. Furthermore, studies show that the prevalence of elevated serum phosphate significantly increases with decreasing income2.
At least 50% of dialysis patients fail to reach the ideal serum phosphate range despite having multiple approved options for management. Studies show the heavy pill burden and high prevalence of side effects contribute to poor adherence and a decreased health-related quality of life3. Patients need effective options that will make phosphorous control easier and more tolerable.
Today, the committee must decide whether the magnitude of tenapanor’s treatment effect is clinically meaningful. Unfortunately, tenapanor’s efficacy does not surpass that of currently approved medications. Data analysis shows that tenapanor causes a mean decrease in serum phosphorous equivalent to about half that of approved treatment options. The effect was similar whether the drug was used alone or in conjunction with other agents.
The committee also must consider the safety and tolerability of this new drug. Tenapanor’s regimen of two to three pills taken twice-a-day contributes to improved tolerability. On the other hand, diarrhea is a common side effect and led to discontinuation of the drug by 16% of trial patients. This data suggests adherence may be a problem in a real-world patient population.
Tenapanor satisfies the need for a simpler approach to treating hyperphosphatemia in chronic kidney disease patients on dialysis. While it may improve health-related quality of life by reducing the pill burden, it is not as effective as currently approved medications. It is unclear how approval of a drug with a limited treatment effect and high rate of side effects will benefit this group of patients facing a high mortality risk.
FDA adcomm votes 9-4 and 10-2 in favor of Ardelyx drug as monotherapy and in combination with phosphate binders.
- Social Determinants of Racial Disparities in CKD | American Society of Nephrology. Accessed November 14, 2022.https://jasn.asnjournals.org/content/27/9/2576
- Gutiérrez OM, Anderson C, Isakova T, et al. Low Socioeconomic Status Associates with Higher Serum Phosphate Irrespective of Race.J Am Soc Nephrol. 2010;21(11):1953-1960. doi:10.1681/ASN.2010020221
- Chiu YW, Teitelbaum I, Misra M, de Leon EM, Adzize T, Mehrotra R. Pill Burden, Adherence, Hyperphosphatemia, and Quality of Life in Maintenance Dialysis Patients.Clin J Am Soc Nephrol. 2009;4(6):1089-1096. doi:10.2215/CJN.00290109