Upacicalcet, an intravenous small molecule, significantly reduced intact parathyroid hormone levels in patients with secondary hyperparathyroidism undergoing hemodialysis, according to pivotal Phase 3 clinical trial results presented at ASN Kidney Week 2026. The therapy demonstrated superior biochemical efficacy compared to placebo.
In Plain English: The Clinical Takeaway
- What it is: Upacicalcet is an intravenous (IV) small-molecule drug administered after each dialysis session to lower intact parathyroid hormone (iPTH) levels.
- How it works: Upacicalcet is removed during the next dialysis session and does not accumulate.
- Why it matters: Because it is cleared during dialysis, healthcare providers can immediately modify subsequent dosing when calcium drops, bypassing the typical week-long or longer clearance delay for the medication.
Phase 3 Trial Design and Efficacy Outcomes in PATH-1 and PATH-2
The clinical evaluation of upacicalcet centers on two randomized, double-blind, placebo-controlled trials: PATH-1, which enrolled 359 participants, and PATH-2, which included 409 participants. The primary efficacy endpoint measured the proportion of patients achieving at least a 30% decrease from baseline in mean intact parathyroid hormone (iPTH) during the assessment period spanning weeks 22 to 27.
In PATH-1, 42.1% of participants treated with upacicalcet met the primary endpoint, compared to 16.8% in the placebo arm. This yielded a statistically significant difference of 25.3% (95% CI, 16.2%–34.5%; P < .0001). The PATH-2 trial mirrored these findings, showing that 43.5% of the active treatment group reached the benchmark versus 17.4% in the control group, representing a 26.1% difference (95% CI, 17.4%–34.8%; P < .0001). Beyond the primary threshold, key secondary endpoints were also cleared, with roughly one in four patients on the drug achieving a 50% or greater reduction in iPTH.
| Trial Metric | PATH-1 (Upacicalcet) | PATH-1 (Placebo) | PATH-2 (Upacicalcet) | PATH-2 (Placebo) |
|---|---|---|---|---|
| Total Participants | 239 | 120 | 271 | 138 |
| Primary Endpoint (≥30% iPTH Drop) | 42.1% | 16.8% | 43.5% | 17.4% |
| Asymptomatic Hypocalcemia | 23.4% | 8.3% | 19.2% | 10.9% |
| Serious Adverse Events | 25.5% | 24.2% | 23.2% | 21.7% |
Safety Profiles and Administration Logistics for Dialysis Care
Managing secondary hyperparathyroidism in end-stage kidney disease typically involves balancing efficacy against side effects. Gastrointestinal symptoms were low and similar between groups.
Asymptomatic decreased blood calcium emerged as the most frequent adverse event, documented in 23.4% of upacicalcet recipients versus 8.3% of placebo controls in PATH-1, and 19.2% compared to 10.9% in PATH-2. However, symptomatic hypocalcemia stayed rare, affecting 0.8% of PATH-1 participants and 2.2% of PATH-2 participants on the active drug.
Upacicalcet is removed during the next dialysis session and does not accumulate. Healthcare professionals can consequently adjust upcoming doses right away when calcium levels drop, avoiding the need to wait seven days or longer for clearance.
Cardiovascular Endpoints and Regulatory Horizons
Because the PATH studies focused solely on biochemical endpoints, information regarding whether upacicalcet prevents fractures or lowers cardiovascular incidents remains unavailable at this time.
To support its therapeutic profile, a separate poster presented at the scientific meeting detailed reductions in fibroblast growth factor 23 (FGF23) and three distinct bone turnover markers. These findings provide metabolic context that will likely inform review committees and regulatory bodies evaluating chronic kidney disease-mineral and bone disorder management. With approximately 500,000 individuals undergoing hemodialysis in the United States, the addressable population remains substantial as developers prepare future regulatory filings.
References
- Kendrick JB, Wolf M, Tirmenstajn Jankovic BH, et al. Efficacy and safety of upacicalcet in patients with secondary hyperparathyroidism (SHPT) on hemodialysis: two randomized controlled clinical trials (RCTs). Presented at: ASN Kidney Week 2026; October 21-25, 2026; Denver, CO. doi:10.1681/ASN.2026s02jzt6e
- Waldron J. Pathalys raises $105M series B to prepare Japan-approved kidney disease drug for FDA. Fierce Biotech. Published August 20, 2024.
Disclaimer: This article is for informational purposes only and does not constitute medical advice, diagnosis, or treatment recommendations.
