Abstract: FR-OR112
Efficacy and Safety of Upacicalcet in Patients with Secondary Hyperparathyroidism (SHPT) on Hemodialysis: Two Randomized Controlled Clinical Trials (RCTs)
Session Information
- Late-Breaking Research Orals: AKI, CKD, CKM, and More
October 23, 2026 | Location: Four Seasons Ballroom 2, Convention Center
Abstract Time: 05:18 PM - 05:30 PM
Category: Bone and Mineral Metabolism
- 502 Bone and Mineral Metabolism: Clinical
Authors
- Kendrick, Jessica B., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Wolf, Myles, Weill Cornell Medicine, New York, New York, United States
- Tirmenstajn Jankovic, Biserka H., General Hospital Zajecar, Belgrade, Serbia
- Camp, Aaron, Launch Therapeutics Inc, Austin, Texas, United States
- Copeland, Eleanor, Launch Therapeutics Inc, Holmfirth, West Yorkshire, United Kingdom
- Dehmel, Bastian, Pathalys Pharma, Raleigh, North Carolina, United States
- Block, Geoff, US Renal Care Inc, Plano, Texas, United States
Background
Secondary hyperparathyroidism (SHPT) is a common complication in patients with end-stage kidney disease undergoing hemodialysis (HD). We examined the efficacy and safety of upacicalcet (PLS240), an intravenous (IV) calcimimetic, vs placebo on serum intact parathyroid hormone (iPTH) levels in patients receiving HD. The studies were designed to isolate the effect of the study drug through the control of confounding background therapies.
Methods
PATH-1 and PATH-2 were identical, phase 3, double-blind, placebo-controlled RCTs conducted in parallel in 768 patients receiving hemodialysis with SHPT and serum iPTH levels ≥400 to ≤1500 pg/mL. Participants were randomized 2:1 to receive IV upacicalcet (n=510) or placebo (n=258) after each HD session for 27 weeks; dosing was titrated based on iPTH and corrected serum calcium. The primary endpoint was the proportion of participants achieving ≥30% decrease from baseline in mean iPTH during the efficacy assessment period (EAP), weeks 22-27.
Results
Mean age was 58.6 years with 66.3% male (PATH-1) and 59.2 years with 59.7% male (PATH-2). The percentage of participants achieving the primary endpoint was significantly higher with upacicalcet vs placebo: in PATH-1, 42.1% (101/239) vs 16.8% (20/120), for a difference in proportions of 25.3% (95% CI 16.2-34.5, p<0.0001); in PATH-2, 43.5% (118/271) vs 17.4% (24/138), for a difference in proportions of 26.1% (95% CI 17.4-34.8, p<0.0001). Adverse events with upacicalcet and placebo were reported in 69.9% vs 60.8% in PATH-1 and 71.6% vs 59.4% in PATH-2, respectively. Serious adverse events were similar between upacicalcet and placebo (PATH-1, 25.5% vs 24.2%; PATH-2, 23.2% vs 21.7%). Rates of gastrointestinal symptoms were low and similar between upacicalcet and placebo. Asymptomatic blood calcium decreased was the most frequent AE: PATH-1, 23.4% vs 8.3%; PATH-2, 19.2% vs 10.9% for upacicalcet and placebo. Symptomatic hypocalcemia with upacicalcet was observed in 0.8% (2/239) in PATH-1 and 2.2% (6/271) in PATH-2.
Conclusion
In two phase 3 RCTs, upacicalcet significantly reduced iPTH vs placebo and was generally well tolerated for the treatment of SHPT in patients receiving HD.
Funding
- Commercial Support – Pathalys Pharma