Both Phase 3 trials of upacicalcet hit their primary endpoint, but the number that matters for how Pathalys will position this drug at the FDA is the gap between arms: roughly 42–44% of patients on upacicalcet achieved at least a 30% reduction in intact parathyroid hormone during the efficacy assessment period, compared with about 17% on placebo. That is not a narrow win in a notoriously difficult-to-treat dialysis population.
The trials, PATH-1 (359 participants) and PATH-2 (409 participants), enrolled adults with secondary hyperparathyroidism and end-stage kidney disease on hemodialysis. Both were randomized, double-blind, and placebo-controlled, with participants receiving upacicalcet or placebo after each dialysis session for 27 weeks. The prespecified secondary endpoints also cleared: roughly one in four patients on upacicalcet reached a 50% or greater PTH reduction, and about 18% in PATH-1 and 17% in PATH-2 landed in the K/DOQI target range of 150–300 pg/mL, versus 8% and 4% on placebo, respectively. Results were presented at ASN Kidney Week 2026 and published simultaneously in the Journal of the American Society of Nephrology.
The safety profile is the part trial designers will study most carefully. Serious adverse event rates were similar between upacicalcet and placebo, and gastrointestinal events, typically the class liability for calcimimetics, were also comparable between arms. Asymptomatic hypocalcemia was the most frequent adverse event (23% vs. 8% in PATH-1; 19% vs. 11% in PATH-2), but symptomatic hypocalcemia stayed below 2% in both active arms. A separate poster reported reductions in FGF23 and three bone turnover markers, which adds metabolic depth to a PTH-centered efficacy story and could matter to payers and guideline committees weighing the drug’s place in chronic kidney disease-mineral and bone disorder management.
Upacicalcet is an IV small molecule given at each dialysis session, a dosing route that avoids the oral adherence problem common in hemodialysis patients. With roughly 500,000 people in the US receiving hemodialysis and SHPT affecting nearly all of them, the addressable population is large. The filing timeline is not yet public, so the number to track now is whether FDA requests any additional data before accepting a submission.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
