Tenapanor as Therapy for Hyperphosphatemia in Maintenance Dialysis Patients: Results from the OPTIMIZE Study
Stuart M. Sprague, Daniel E. Weiner, David P. Tietjen, Pablo E. Pérgola, Steven Fishbane, Geoffrey A. Block, Arnold L. Silva, Stephen Z. Fadem, Robert I. Lynn, George Z. Fadda, Lynae Pagliaro, Suling Zhao, Susan Edelstein, David M. Spiegel, David P. Rosenbaum
Abstract
Key Points Tenapanor, a first-in-class local inhibitor of sodium/hydrogen exchanger isoform 3, acts as a phosphate absorption inhibitor by decreasing paracellular phosphate absorption. Tenapanor alone or with phosphate binders achieved P ≤ 5.5 mg/dl over 10 weeks in 34%–38% of patients taking phosphate binders at baseline. Tenapanor can help adults with CKD on maintenance dialysis achieve normal serum phosphate concentrations. Background OPTIMIZE was a randomized, open-label study evaluating different tenapanor initiation methods. OPTIMIZE evaluated tenapanor alone and in combination with phosphate binders (PBs) to achieve target serum phosphate (P) ≤5.5 mg/dl. Methods Patients with inadequately controlled P receiving maintenance dialysis from 42 US locations who were taking PBs with baseline P > 5.5 mg/dl and ≤ 10.0 mg/dl, or were PB-naive with baseline P > 4.5 mg/dl and ≤ 10.0 mg/dl, were included in OPTIMIZE. Participants taking PBs at baseline were randomized to switch from PBs to tenapanor ( Straight Switch ; n =151) or reduce PB dosage by ≥50% and add tenapanor ( Binder Reduction ; n =152); PB-naive patients started tenapanor alone ( Binder-Naive ; n =30). Participants received tenapanor 30 mg twice a day for 10 weeks (part A), followed by an elective, 16-week open-label extension (part B). Outcomes included changes from baseline in P, intact fibroblast growth factor 23, parathyroid hormone, serum calcium, and medication burden; patient-reported outcomes; and safety. Results By part A end point, 34.4% ( Straight Switch ), 38.2% ( Binder Reduction ), and 63.3% ( Binder-Naive ) of patients achieved P ≤ 5.5 mg/dl. Mean P reduction and median pill burden reduction from baseline to part A end point were 0.91±1.7 mg/dl and 4 pills/d for the Straight Switch and 0.99±1.8 mg/dl and 1 pill/d for the Binder Reduction group. The mean P reduction for Binder-Naive patients was 0.87±1.5 mg/dl. Among Straight Switch and Binder Reduction patients who completed patient experience questionnaires, 205 of 243 (84.4%) reported an improved phosphate management routine. Diarrhea was the most common adverse event (133 of 333 [39.9%]). Conclusions Tenapanor as monotherapy or in combination with PBs effectively lowered P toward the target range in patients who were PB-naive or who were not at goal despite PB use. Clinical Trial registration number NCT04549597.