Ardelyx makes presentations, moves stock and upcoming PDUFA

Kidneys and Cash

As long as insiders follow disclosure rules, it is not a problem for company leaders, such as directors of the board, to buy and sell stock in the company. At Ardelyx Inc., a biopharmaceutical company focused on developing innovative first-in-class medicines to improve treatment for people with kidney and cardiorenal diseases, the biggest insider purchase over the last year was by Independent Chairman David Mott for US $1 million worth of shares, at about US $5.89 per share. This purchase was made at well below the current price of US $7.40. The average price per share was US $6.33.

Ardelyx insiders own about US $13 million worth of shares. That equates to 1.7 percent of the company. During the last quarter there was substantial insider selling of Ardelyx shares.

Meanwhile, Ardelyx has done two recent presentations highlighting new tenapanor data at the European Renal Association — European Dialysis and Transplant Association (ERA-EDTA) Virtual Congress 2021. Interim data from the company’s ongoing OPTIMIZE study shows that tenapanor can play a central role across the hyperphosphatemia treatment paradigm in adult patients with chronic kidney disease on dialysis, enabling greater achievement of phosphorus targets in binder-treated patients with phosphorus above 5.5 and control of serum phosphorus in binder-naïve patients. In another presentation, the company reported that patients who were on tenapanor had a smaller percentage of deaths and hospitalizations than those on the phosphate binder, sevelamer, in the long-term Phase 3 PHREEDOM study.

Hyperphosphatemia is a serious condition resulting in an abnormally elevated level of phosphorus in the blood that is estimated to affect the vast majority of the 550,000 patients in the United States with CKD on dialysis. The kidney is the organ responsible for regulating phosphorus levels, but when kidney function is significantly impaired, phosphorus is not adequately eliminated from the body. As a result, hyperphosphatemia is a nearly universal condition among people with CKD on dialysis with internationally recognized KDIGO treatment guidelines that recommend lowering elevated phosphate levels toward the normal range (2.5–4.5mg/dL).

As David Rosenbaum, Ph.D. chief development officer, explained, “Our OPTIMIZE study was designed to evaluate multiple methods for integrating the novel blocking mechanism of tenapanor into the hyperphosphatemia treatment paradigm with the goal of increasing the proportion of patients able to achieve target phosphorus levels. We are extremely pleased with the interim results demonstrating that tenapanor use resulted in approximately 50% of previously uncontrolled patients achieving target phosphorus levels when either switched to tenapanor monotherapy or with the addition of tenapanor with a concurrent reduction in binder dose. The interim results also demonstrated that two-thirds of binder-naïve patients who started on tenapanor monotherapy were able to achieve and/or maintain target phosphorus levels.”

According to Dr. Steven Fishbane, chief of nephrology, Northwell Health, and professor of medicine, Zucker School of Medicine, “I am excited by these results that demonstrate both binder-treated and binder-naïve patients may be better able to achieve target phosphorus levels by applying a blocking mechanism approach as an integral component to hyperphosphatemia management, reflecting the important role of tenapanor across a broad range of patients and treatment regimen scenarios.”

As of the interim analysis, 232 patients had been randomized in the OPTIMIZE study to Cohort 1 (straight switch to tenapanor from binder, n=116) or Cohort 2 (start tenapanor and reduce binder dose by 50%, n=116) and 27 binder naïve individuals had been enrolled into Cohort 3 and started on tenapanor. Among participants that had completed 8 weeks of treatment, 47.7 percent in Cohort 1, 47.8 percent in Cohort 2 achieved, and 66.7 percent in Cohort 3 achieved and/or maintained recommended serum phosphorus (s-P) levels ≤ 5.5 mg/dL at week 8. Furthermore, subgroup analyses on randomized participants in Cohort 1 and Cohort 2 demonstrated that 53.3 percent of participants with a baseline s-P > 5.5 and ≤ 6.5 mg/dL, 51.7 percent of participants with a baseline s-P > 6.5 and ≤ 7.5, and 38.7 percent of participants with a baseline s-P > 7.5 mg/dL achieved an s-P ≤ 5.5 mg/dL at week 8. Diarrhea, the most common adverse event in this study, was reported with an incidence rate of 29.3 percent in Cohort 1, 36.2 percent in Cohort 2, and 14.8 percent in Cohort 3. Five participants (1.9 percent), none from Cohort 3, experienced diarrhea that led to study drug discontinuation.

OPTIMIZE is a randomized, open label study, which will include approximately 330 patients with chronic kidney disease (CKD) on dialysis with hyperphosphatemia. The study is designed to evaluate different methods of initiating tenapanor therapy across the hyperphosphatemia treatment paradigm to optimize phosphorus management in both binder-naïve and binder-treated patients. The objective is to evaluate the ability of tenapanor, with its novel blocking mechanism, administered as core therapy for the treatment of hyperphosphatemia in adult patients with CKD on dialysis, alone or in combination with phosphate binders, to achieve target serum phosphorus (s-P) levels ≤5.5 mg/dL.

The 52-week PHREEDOM study consisted of a 26-week, open-label, randomized treatment period with a 12-week placebo-controlled randomized withdrawal period, followed by a 14-week open label safety extension period. Maintenance dialysis patients with serum phosphorus ≥ 6.0 mg/dL and a 1.5 mg/dL increase in serum phosphorus following phosphate binder washout were randomized 3:1 to receive tenapanor 30 mg twice daily or sevelamer carbonate, dosed per package insert. Sevelamer was used as a safety control for comparisons of serious adverse events/hospitalizations. Comparing patients who only received tenapanor versus those who only received sevelamer, the data demonstrated a lower overall incidence of death (3.1 percent versus 3.6 percent) as well as serious adverse events leading to hospitalization (22.5 percent versus 35.8 percent) and a shorter mean duration of hospitalization (11.5 days versus 13.5 days) in patients treated with tenapanor (n=293) compared to sevelamer (n=137), respectively.

The primary efficacy endpoint of the study was the difference in change in serum phosphorus between the pooled tenapanor-treated patients and placebo-treated patients in the efficacy analysis set from the end of the 26-week treatment period to the endpoint visit of the 12-week randomized withdrawal period. The efficacy analysis set (n=131) included patients who completed the 26-week treatment period and achieved a 1.2 mg/dL decrease in serum phosphorus in the same period.

Ardelyx is advancing tenapanor, a novel product candidate to control serum phosphorus in adult patients with CKD on dialysis, for which the company’s NDA is currently under review by the FDA, with a PDUFA date of July 29, 2021. Ardelyx is also advancing RDX013, a potassium secretagogue, for the potential treatment of elevated serum potassium, or hyperkalemia, a problem among certain patients with kidney and/or heart disease and has an early-stage program in metabolic acidosis, a serious electrolyte disorder in patients with CKD.

In addition, Ardelyx received FDA approval of IBSRELA® (tenapanor) on September 12, 2019 for Constipation-predominant irritable bowel syndrome (IBS-C). Ardelyx has established agreements with Kyowa Kirin in Japan, Fosun Pharma in China and Knight Therapeutics in Canada for the development and commercialization of tenapanor in their respective territories.