Upasita (upacicalcet) / JW Pharma, Suzuken, Pathalys Pharma, Eisai, Kissei, Tasly - LARVOL DELTA

Effects of Switching from Etelcalcetide to Upacicalcet in Patients on Hemodialysis with Secondary Hyperparathyroidism (KIDNEY WEEK 2025) - "Serum levels of corrected calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH), and the dose of maxacalcitol were assessed at three and six months after switching to upacicalcet. Multiple regression analysis revealed that the change in iPTH was related to the change in P levels. Conclusion These findings suggested that upacicalcet may be a useful option for managing serum P levels in hemodialysis patients with SHPT."

Clinical • Endocrine Disorders • Renal Disease • Secondary Hyperparathyroidism

Upacicalcet Preserves Albumin Levels in Patients on Hemodialysis with Secondary Hyperparathyroidism: A Post-hoc Analysis of a Randomized Trial. (PubMed, Am J Nephrol) - "These findings raise the hypothesis that PTH suppression with upacicalcet mitigates the gradual decline in serum albumin levels over time. Further studies are warranted to investigate the long-term impact of PTH control on protein-energy wasting and related clinical outcomes."

Journal • Retrospective data • Endocrine Disorders • Renal Disease • Secondary Hyperparathyroidism

Impact of upacicalcet on bone metabolism in hemodialysis patients with secondary hyperparathyroidism: a post-hoc analysis. (PubMed, JBMR Plus) - "Upacicalcet treatment reduced PTH levels in HD patients with SHPT, regardless of baseline BAP levels. The concurrent increase in the BAP/TRACP-5b ratio with upacicalcet suggests that this agent may exert direct effects on bone metabolism, in addition to its role in suppressing parathyroid activity."

Journal • Retrospective data • Endocrine Disorders • Renal Disease • Secondary Hyperparathyroidism • TRAP

PATH-2: Parathyroid Hormone (PTH) Attenuation Trial in Hemodialysis-2 (clinicaltrials.gov) - P3 | N=412 | Completed | Sponsor: Pathalys Pharma | Active, not recruiting ➔ Completed

Trial completion • Chronic Kidney Disease • Endocrine Disorders • Nephrology • Renal Disease • Secondary Hyperparathyroidism

PATH-1: Parathyroid Hormone (PTH) Attenuation Trial in Hemodialysis-1 (clinicaltrials.gov) - P3 | N=362 | Completed | Sponsor: Pathalys Pharma | Active, not recruiting ➔ Completed

Trial completion • Chronic Kidney Disease • Endocrine Disorders • Nephrology • Renal Disease • Secondary Hyperparathyroidism

The effects of switching from etelcalcetide to upacicalcet in hemodialysis patients with secondary hyperparathyroidism. (PubMed, Clin Nephrol) - "These findings suggested that upacicalcet may be a useful option for managing serum P levels in hemodialysis patients with SHPT."

Journal • Endocrine Disorders • Renal Disease • Secondary Hyperparathyroidism

Upacicalcet Preserves Albumin Levels in Hemodialysis Patients with Secondary Hyperparathyroidism: A Post-hoc Analysis of a Randomized Trial (ERA 2025) - "Our results indicate that PTH suppression with upacicalcet mitigates the gradual decline in albumin levels over time. Further research is needed to explore the long-term impact of PTH control on wasting and related outcomes."

Clinical • Retrospective data • Endocrine Disorders • Renal Disease • Secondary Hyperparathyroidism

Combination Treatment With Intravenous and Oral Calcimimetics for Secondary Hyperparathyroidism in Hemodialysis Patients Who Decline Parathyroidectomy. (PubMed, Cureus) - "The combination of intravenous and oral calcimimetics is an effective therapeutic option for managing SHPT in patients on HD who refuse PTX. While promising, the long-term safety and potential risks of this approach, including the occurrence of malignancies, warrant further investigation in larger prospective studies."

Journal • Cardiovascular • Endocrine Disorders • Gastrointestinal Disorder • Kidney Cancer • Oncology • Renal Cell Carcinoma • Secondary Hyperparathyroidism • Solid Tumor

Pharmacological properties and clinical trial results of the novel calcium-sensing receptor agonist upacicalcet sodium hydrate (Upacita® intravenous injection for dialysis) (PubMed, Nihon Yakurigaku Zasshi) - "In clinical trials, upacicalcet demonstrated efficacy and safety in patients with SHPT undergoing hemodialysis, as assessed in domestic Phase I/II trial (AJ1001 trial), Phase II trial (AJ1002 trial), Phase III placebo-controlled trial (AJ1004 trial), and Phase III long-term administration trial (AJ1003 trial). Upacicalcet was approved in June 2021 for the treatment of secondary hyperparathyroidism (SHPT) in patients undergoing hemodialysis and was launched in August of the same year."

Journal • Endocrine Disorders • Orthopedics • Secondary Hyperparathyroidism

Impact of Upacicalcet on Bone Metabolism in Patients on Hemodialysis Who Have Secondary Hyperparathyroidism: Post Hoc Analysis Based on Baseline Alkaline Phosphatase (KIDNEY WEEK 2024) - "Upacicalcet decreased serum intact PTH concentration regardless of the degree of bone turnover. The effect was more pronounced in patients with low BAP levels, however, Upacicalcet may improve bone turnover in HD patients with any bone metabolism state."

Clinical • Retrospective data • Endocrine Disorders • Secondary Hyperparathyroidism • TRAP

New calcimimetics for secondary hyperparathyroidism in CKD G5D: do they offer advantages? (PubMed, J Nephrol) - "To address the problem of oral compliance, Etelcalcetide, a small synthetic polycationic peptide IV calcimimetic was introduced in 2017...Several structural modifications were introduced in cinacalcet to produce a new compound called evocalcet...Finally, a novel non-peptidic injectable calcimimetic agent, upacicalcet, became available in Japan in 2021. This agent has greater clearance by hemodialysis and shows no effect on gastric emptying. More studies are needed comparing the old calcimimetics to the new ones to establish their future role in the treatment of secondary hyperparathyroidism in chronic kidney disease (CKD) G5D."

Journal • Review • Chronic Kidney Disease • Endocrine Disorders • Gastrointestinal Disorder • Nephrology • Secondary Hyperparathyroidism

Long-term Efficacy and Safety of Upacicalcet in Japanese Hemodialysis Patients with Secondary Hyperparathyroidism: Open-label 52-week Study. (PubMed, Am J Nephrol) - "Conclusion This is the first study to show that a calcimimetic improves serum P and cCa control without inducing severe hypocalcemia in patients with iPTH levels ≤300 pg/mL. Upacicalcet is efficacious in HD patients with mild-to-severe SHPT, with few safety concerns."

Journal • Endocrine Disorders • Renal Disease • Secondary Hyperparathyroidism • FGF23

PATH-1: Parathyroid Hormone (PTH) Attenuation Trial in Hemodialysis-1 (clinicaltrials.gov) - P3 | N=363 | Active, not recruiting | Sponsor: Pathalys Pharma | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Kidney Disease • Endocrine Disorders • Nephrology • Renal Disease • Secondary Hyperparathyroidism

PATH-2: Parathyroid Hormone (PTH) Attenuation Trial in Hemodialysis-2 (clinicaltrials.gov) - P3 | N=412 | Active, not recruiting | Sponsor: Pathalys Pharma | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Kidney Disease • Endocrine Disorders • Nephrology • Renal Disease • Secondary Hyperparathyroidism

Calcimimetics treatment strategy for serum calcium and phosphate management in patients with secondary hyperparathyroidism undergoing dialysis: A systematic review and meta-analysis of randomized studies. (PubMed, Ther Apher Dial) - "Calcimimetics significantly reduced serum calcium and phosphate levels compared to placebo in patients with secondary hyperparathyroidism undergoing dialysis, independent of therapeutic strategy or concomitant vitamin D treatment."

Journal • Retrospective data • Review • Endocrine Disorders • Secondary Hyperparathyroidism

Multicentre, open-label, randomised, controlled trial to compare early intervention with calcimimetics and conventional therapy in preventing coronary artery calcification in patients with secondary hyperparathyroidism (UPCOMING): a study protocol. (PubMed, BMJ Open) - "Therefore, this study will evaluate the efficacy and safety of early intervention with upacicalcet, a calcimimetic used to prevent coronary artery calcification in this patient population...Study results will be presented in academic meetings and peer-reviewed academic journals. jRCTs041220126."

Journal • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Endocrine Disorders • Heart Failure • Musculoskeletal Diseases • Myocardial Infarction • Orthopedics • Secondary Hyperparathyroidism

PATH-2: Parathyroid Hormone (PTH) Attenuation Trial in Hemodialysis-2 (clinicaltrials.gov) - P3 | N=375 | Recruiting | Sponsor: Pathalys Pharma

Trial completion date • Trial primary completion date • Chronic Kidney Disease • Endocrine Disorders • Nephrology • Renal Disease • Secondary Hyperparathyroidism

PATH-1: Parathyroid Hormone (PTH) Attenuation Trial in Hemodialysis-1 (clinicaltrials.gov) - P3 | N=375 | Recruiting | Sponsor: Pathalys Pharma

Trial completion date • Trial primary completion date • Chronic Kidney Disease • Endocrine Disorders • Nephrology • Renal Disease • Secondary Hyperparathyroidism

Phase 2 study of upacicalcet in Japanese haemodialysis patients with secondary hyperparathyroidism: an intraindividual dose-adjustment study. (PubMed, Clin Kidney J) - "The serum cCa level of patients who interrupted upacicalcet treatment at a serum cCa level of <7.5 mg/dL recovered to ≥7.5 mg/dL immediately after the interruption. In haemodialysis patients with SHPT, upacicalcet doses of 25-300 μg for 52 weeks were found to be highly effective and well-tolerated, with minor safety concerns."

Journal • P2 data • Endocrine Disorders • Renal Disease • Secondary Hyperparathyroidism

Impact of Dialysate Calcium Concentration on Bone Metabolism in Relation to Different Calcimimetics (KIDNEY WEEK 2023) - "Changes in bone mineral density were assessed over six months using the Dual-Energy X-ray Absorptiometry (DEXA) Imaging Protocol. In patients with a calcium concentration of 2.5 mEq/L dialysate, evocalcet and etelcalcetide resulted in an increase in bone mineral density by 4.4% and 1.3%, respectively. Conversely, upacicalcet showed a decrease in bone mineral content by 3.3%... Calcimimetics exert significant effects on bone metabolism in addition to their ability to lower iPTH levels. However, this effect may vary depending on the concentration of calcium in the dialysate."

Endocrine Disorders • Secondary Hyperparathyroidism

Efficacy and Safety of Upacicalcet in Hemodialysis Patients with Secondary Hyperparathyroidism: A Randomized Placebo-Controlled Trial. (PubMed, Clin J Am Soc Nephrol) - P3 | "Upacicalcet, a novel injectable calcimimetic, is effective and safe for secondary hyperparathyroidism patients receiving HD."

Journal • Endocrine Disorders • Gastrointestinal Disorder • Renal Disease • Secondary Hyperparathyroidism • COL1A2 • FGF23 • TRAP

Pharmacological profile of upacicalcet, a novel positive allosteric modulator of calcium-sensing receptor, in vitro and in vivo. (PubMed, Eur J Pharmacol) - "We compared upacicalcet with other calcimimetics (etelcalcetide or cinacalcet) and examined its in vitro and in vivo characteristics in terms of its human CaSR agonistic activity, its efficacy in normal and CKD rats after a single administration, and its effect on gastric emptying in rats. Furthermore, upacicalcet did not affect gastric emptying in normal rats when administered up to a dose of 10 mg/kg (300-fold higher than the dose affecting serum iPTH levels), while the administration of cinacalcet significantly slowed gastric emptying by approximately 50%. These findings suggest that upacicalcet has potential as an alternative calcimimetic agent with good pharmacological properties and a lower risk of hypocalcemia and gastrointestinal complications."

Journal • Preclinical • Chronic Kidney Disease • Endocrine Disorders • Gastrointestinal Disorder • Nephrology • Secondary Hyperparathyroidism

PATH-2: Parathyroid Hormone (PTH) Attenuation Trial in Hemodialysis-2 (clinicaltrials.gov) - P3 | N=375 | Recruiting | Sponsor: Pathalys Pharma | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Kidney Disease • Endocrine Disorders • Nephrology • Renal Disease • Secondary Hyperparathyroidism

PATH-1: Parathyroid Hormone (PTH) Attenuation Trial in Hemodialysis-1 (clinicaltrials.gov) - P3 | N=375 | Recruiting | Sponsor: Pathalys Pharma | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Kidney Disease • Endocrine Disorders • Nephrology • Renal Disease • Secondary Hyperparathyroidism

PATH-2: PTH Attenuation Trial in Hemodialysis-2 (clinicaltrials.gov) - P3 | N=375 | Not yet recruiting | Sponsor: Pathalys Pharma

New P3 trial • Chronic Kidney Disease • Endocrine Disorders • Nephrology • Renal Disease • Secondary Hyperparathyroidism