Nephrology · 3 h ago
Upacicalcet lowers parathyroid hormone in two hemodialysis trials
Two randomized, double-blind phase 3 trials compared intravenous upacicalcet with placebo in 768 hemodialysis patients with secondary hyperparathyroidism. At 27 weeks, more patients receiving upacicalcet achieved at least a 30% reduction in intact parathyroid hormone, while low calcium and dose interruptions were more frequent.
- Two phase 3 trials enrolled 768 hemodialysis patients.
- iPTH response was higher with upacicalcet in both trials.
- Low calcium and dose interruptions were more frequent.
- Symptomatic hypocalcemia was infrequent; GI events were similar.
PATH-1 and PATH-2 were parallel, placebo-controlled phase 3 trials involving 768 adults receiving hemodialysis with secondary hyperparathyroidism and intact parathyroid hormone (iPTH) levels of 400–1,500 pg/ml. Participants received dose-titrated intravenous upacicalcet (n=510) or placebo (n=258) after dialysis three times weekly for 27 weeks. The primary endpoint was a reduction of at least 30% in mean iPTH during weeks 22–27.
The primary endpoint was reached by 42.1% versus 16.8% of participants in PATH-1 and 43.5% versus 17.4% in PATH-2, respectively (both P<0.001). Serious adverse event rates were similar between groups. Corrected calcium below 7.5 mg/dl was more common with upacicalcet: 31% versus 12% in PATH-1 and 45% versus 19% in PATH-2. Dose interruptions were also more frequent. Investigator-attributed symptomatic hypocalcemia occurred in 0.8% and 2% of upacicalcet recipients in the two trials, and in no placebo recipients; gastrointestinal event rates were similar.
The findings support an iPTH-lowering effect in the studied dialysis population, but the trials do not establish effects on clinical outcomes such as fractures or mortality. The increased frequency of low calcium and treatment interruptions is relevant to safety monitoring. Upacicalcet is approved in Japan; the source does not report approval elsewhere.
In practice
For adults on hemodialysis with secondary hyperparathyroidism and iPTH of 400–1,500 pg/ml, these two 27-week placebo-controlled phase 3 trials found that upacicalcet increased the likelihood of achieving at least a 30% iPTH reduction. The results establish a biochemical effect, not improvement in patient-important outcomes. Low corrected calcium and dose interruptions were more frequent, although reported symptomatic hypocalcemia was uncommon. These findings alone do not establish a practice change or approval outside Japan.
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Journal of the American Society of Nephrology: Efficacy and Safety of Upacicalcet in Hemodialysis Patients with Secondary Hyperparathyroidism ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.