Tenapanor as Therapy for Hyperphosphatemia in Maintenance Dialysis Patients: Results from the OPTIMIZE Study.

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 ≤ 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 > 5.5 mg/dl and ≤ 10.0 mg/dl, or were PB-naive with baseline > 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 (; =151) or reduce PB dosage by ≥50% and add tenapanor (; =152); PB-naive patients started tenapanor alone (; =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% (), 38.2% (), and 63.3% () of patients achieved ≤ 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 and 0.99±1.8 mg/dl and 1 pill/d for the group. The mean P reduction for patients was 0.87±1.5 mg/dl. Among and 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.