Ardelyx Announces Presentations at ERA-EDTA Virtual Congress 2021
FREMONT, Calif. and WALTHAM,
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 >5.5 and control of serum phosphorus in binder-naïve patients.
In a separate 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.
"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," said
Ardelyx Presentations at ERA-EDTA
Abstract Title: A Randomized, Open-Label Study to Evaluate Potential Real-World Use of Tenapanor as the Core Therapy in the Treatment of Hyperphosphatemia in Patients with Chronic Kidney Disease on Dialysis (OPTIMIZE)
Session Title: Late Breaking Clinical Trials
Format: Mini Oral Presentation (available
OPTIMIZE Oral Presentation
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% in Cohort 1, 47.8% in Cohort 2 achieved, and 66.7% 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% of participants with a baseline s-P > 5.5 and ≤ 6.5 mg/dL, 51.7% of participants with a baseline s-P > 6.5 and ≤ 7.5, and 38.7% 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% in Cohort 1, 36.2% in Cohort 2, and 14.8% in Cohort 3. Five participants (1.9%), none from Cohort 3, experienced diarrhea that led to study drug discontinuation.
Abstract Title: Long-Term Safety of Tenapanor for the Control of Serum Phosphorus in Patients with CKD on Dialysis
Session Title: Bones & Outcomes in CKD
Format: Oral Presentation (
PHREEDOM Oral Presentation
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% versus 3.6%) as well as serious adverse events leading to hospitalization (22.5% versus 35.8%) 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.
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. Patients with s-P >5.5 and ≤10.0 mg/dL during stable phosphate binder treatment are being randomized into in a 1:1 ratio to two different treatment cohorts: Cohort 1, a straight switch approach is used where current phosphate binder treatment is discontinued and patients are switched to tenapanor 30 mg twice daily (BID) or Cohort 2 (50% binder reduction), where current phosphate binder dose is reduced by at least 50% and tenapanor therapy is initiated at 30 mg BID. After week 2, investigators can adjust phosphate binder dose to achieve a s-P level of ≤5.5 mg/dL with tenapanor as the core therapy and binders as adjunctive. A third cohort comprised of phosphate binder naïve patients with s-P >4.5 and ≤10.0 mg/dL (Cohort 3) were enrolled and initiated tenapanor 30 mg BID.
PHREEDOM is a one-year Phase 3 study with a 26-week open-label treatment period, a 12-week double-blind, placebo-controlled randomized withdrawal period, and a 14-week open-label safety extension period. The study randomized a total of 564 patients with CKD on dialysis who had a serum phosphorus level between 6.0 mg/dL and 10.0 mg/dL and had an increase in serum phosphorus of at least 1.5 mg/dL after an up to 3-week phosphate binder wash-out period. Patients were randomized 3:1 to either the tenapanor arm (n=423, n=408 intent to treat) or the active safety control arm (sevelamer n=141). Patients randomized to the active safety control arm were treated with sevelamer for 52 weeks. Patients in the tenapanor arm received tenapanor twice daily at a starting dose of 30 mg with dose adjustments allowed based on serum phosphorus level and gastrointestinal tolerability. At the end of the 26-week treatment period, patients in the tenapanor arm were randomized 1:1 to enter the randomized withdrawal period and either remain on the tenapanor dose they were taking or receive placebo. After the randomized withdrawal period, patients continued on the study for an additional three months as part of the long-term safety extension. Patients in the active safety control arm received sevelamer at an initial dose based on its package insert with dose changes allowed at the discretion of the principal investigator for up to one year.
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.
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
Forward Looking Statements
To the extent that statements contained in this press release are not descriptions of historical facts regarding
View original content to download multimedia:http://www.prnewswire.com/news-releases/ardelyx-announces-presentations-at-era-edta-virtual-congress-2021-301306497.html
Kimia Keshtbod , email@example.com, OR Sylvia Wheeler, Wheelhouse Life Science Advisors, firstname.lastname@example.org OR Alex Santos, Wheelhouse Life Science Advisors, email@example.com