Orkedia (evocalcet) / Tanabe Pharma, Kyowa Kirin - LARVOL DELTA

Space-velocity-governed chemoselective pseudo-oxidation: a convergent flow platform for the synthesis of evocalcet. (PubMed, RSC Adv) - "The integration of these three hydrogen-mediated transformations enabled the formation of the evocalcet ester in 79% yield, followed by hydrolysis to furnish evocalcet in high purity. This study establishes SV-controlled redox modulation as a powerful, general strategy for the sustainable and selective synthesis of complex, functionalized chemical scaffolds."

Journal

Calcimimetics and CaSR signaling in CKD-MBD: bone-immune-vascular crosstalk and therapeutic potential. (PubMed, Front Immunol) - "Calcimimetics, including cinacalcet, etelcalcetide, and evocalcet, are established CaSR-targeting therapies for secondary hyperparathyroidism in dialysis patients. We emphasize established clinical effects while distinguishing them from mechanistic hypotheses, including direct NLRP3 inflammasome suppression, Th17/Treg rebalancing, macrophage M1-to-M2 polarization, osteocyte connexin-43/DAMP regulation, and hematopoietic niche restoration, which remain insufficiently validated in human CKD. We propose an integrated bone-vascular-immune framework and identify biomarker-guided and precision-medicine strategies for future calcimimetic research."

Journal • Review • Chronic Kidney Disease • Endocrine Disorders • Inflammation • Nephrology • Orthopedics • Secondary Hyperparathyroidism • CASR • FGF23 • NFATC1 • NLRP3 • TNFRSF11B

A CASE OF PRIMARY HYPERPARATHYROIDISM IN WHICH CALCIMIMETICS WAS INEFFECTIVE BUT BISPHOSPHONATE ALONE WAS EFFECTIVE (ISN-WCN 2026) - "Treatment with both zoledronic acid (4 mg intravenously) and the calcimimetic agent evocalcet (1 mg/day) was started to control severe, refractory hypercalcemia. She was discharged on hospital day 21.Conclusion What was most remarkable about this case was that, on the morning of surgery, the serum iPTH level had further increased to 3880 pg/mL despite evocalcet treatment, which is indicated for primary hyperparathyroidism. The negative feedback mechanism via the calcium-sensing receptor was presumed to have failed, and only the bisphosphonate therapy proved effective.In conclusion, in cases of extreme and refractory hypercalcemia due to markedly elevated iPTH, there may be instances in which calcimimetics are ineffective, whereas bisphosphonate therapy alone is highly effective."

Clinical • Acute Kidney Injury • Anorexia • Endocrine Disorders • Metabolic Disorders • Nephrology • COL1A2 • TRAP

LOWER INCIDENCE OF HYPOCALCEMIA IN HEMODIALYSIS PATIENTS RECEIVING EVOCALCET COMPARED WITH ETELCALCETIDE: A MULTICENTER COHORT STUDY (MBD-NEXT) (ISN-WCN 2026) - "TH has received personal fees from Kissei Pharmaceutical and KKC, and grants from KKC. The remaining author has nothing to disclose.I did not use generative AI and AI-assisted technologies in the writing process."

Clinical • Endocrine Disorders • Renal Disease

Evocalcet improved the PTH-calcium setpoint and suppressed parathyroid proliferation in mice model of primary hyperparathyroidism. (PubMed, J Bone Miner Metab) - "Evocalcet, similar to cinacalcet, lowers the PTH-calcium setpoint and inhibits parathyroid cell proliferation in a mouse model of primary hyperparathyroidism. These findings suggest that evocalcet may not only reduce PTH secretion but also attenuate disease progression in hyperparathyroidism."

Journal • Preclinical • Endocrine Disorders • Secondary Hyperparathyroidism • CASR • CCND1 • VDR

Quantitative LC-MS/MS Assay for Evocalcet in Human Plasma: Comparative Pharmacokinetic Evaluation in Fasted and Fed Healthy Chinese Volunteers. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "Moreover, hyperthyroid patients exhibited longer Tmax and t1/2, along with increased AUC0-t and AUC0-∞ values, compared to healthy individuals. These findings offer valuable methodological insights and pharmacokinetic data to advance clinical research on evocalcet, thereby contributing to a deeper understanding of its safety and efficacy profile."

Journal • PK/PD data • Endocrine Disorders • Hypoparathyroidism

Medically Managed Dropped Head Syndrome: Outcomes in Isolated Neck Extensor Myopathy and Primary Hyperparathyroidism-related Myopathy. (PubMed, Intern Med) - "Conclusion INEM is the predominant etiology of DHS at initial presentation, and immunotherapy is an effective management strategy, especially with early intervention. PHPT-related myopathy represents another important etiology of DHS, with a favorable response to medical therapy with evocalcet."

Journal • Endocrine Disorders • Inflammation • Myositis

Effectiveness of evocalcet for hypercalcemia in patients with primary hyperparathyroidism. (PubMed, Endocr J) - "The study included 26 patients with PHPT and hypercalcemia treated with evocalcet (7 switched from cinacalcet) for at least 24 months. Evocalcet maintained its calcium-lowering effect for over 24 months in patients with PHPT, suggesting its potential as a medical treatment for surgery-ineligible patients. Careful monitoring of BMD is necessary during long-term evocalcet treatment to prevent worsening of osteoporosis."

Journal • Endocrine Disorders • Metabolic Disorders • Osteoporosis • Rheumatology

Evocalcet: A New Oral Calcimimetics for Dialysis Patients with Secondary Hyperparathyroidism (KSN 2025) - "Sponsored by DKSH"

Clinical • Endocrine Disorders • Secondary Hyperparathyroidism

Rapid development of diffuse hepatic calcification in a patient with congenital hepatic fibrosis and secondary hyperparathyroidism. (PubMed, Clin J Gastroenterol) - "Treatment with evocalcet and dialysis regimen adjustments led to improvements in laboratory parameters...Progressive hepatic calcification ultimately led to a decline in liver function, necessitating simultaneous brain-dead donor liver and kidney transplantation 17 months after the initial admission. This case highlights the complex interplay between congenital hepatic fibrosis, mineral metabolism disturbances associated with dialysis, and the rare occurrence of rapidly progressing hepatic calcification."

Journal • Chronic Kidney Disease • CNS Disorders • Endocrine Disorders • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Hematological Disorders • Hepatic Encephalopathy • Hepatology • Immunology • Infectious Disease • Metabolic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease • Secondary Hyperparathyroidism • Transplantation

Primary Hyperparathyroidism with Severe Vitamin D Deficiency in Chronic Kidney Disease. (PubMed, Intern Med) - "Hemodialysis and evocalcet failed to control the calcium levels, but denosumab effectively reduced hypercalcemia. This case highlights the importance of vitamin D assessment in PHPT, as its metabolism can vary. Denosumab may be a viable treatment option for calcimimetic hypercalcemia."

Journal • Chronic Kidney Disease • Endocrine Disorders • Metabolic Disorders • Nephrology • Renal Disease

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

Recurrent syncope attributed to torsade de pointes induced by worsened long QT interval after switching from peritoneal dialysis to hemodialysis: A case report. (PubMed, J Cardiol Cases) - "Evocalcet was discontinued because it is known to induce long QT, and bisoprolol was initiated. The worsening of long QT is mainly attributed to fluctuation in potassium levels before and after HD. Thus, carefully monitoring the QT interval and changes in the serum potassium level is crucial, particularly, when initiating HD."

Journal • Cardiovascular • Chronic Kidney Disease • Renal Disease

Hypertension Rounds: Successful treatment with evocalcet for resistant hypertension induced by asymptomatic primary hyperparathyroidism. (PubMed, Am J Hypertens) - No abstract available

Journal • Cardiovascular • Endocrine Disorders • Hypertension

Successful Treatment With Evocalcet Against Familial Hypocalciuric Hypercalcemia Type 3 (FHH3) Identified by AP2S1 Gene Mutation (p.Arg15Leu). (PubMed, Case Rep Endocrinol) - "Treatment with evocalcet gradually decreased and normalized the serum Ca level, and promoted improvements in bone metabolism, without serious adverse events. Evocalcet may be a promising therapeutic candidate for symptomatic FHH3."

Journal • CNS Disorders • Developmental Disorders • Endocrine Disorders • Genetic Disorders • Metabolic Disorders • Psychiatry • ARG1

Severe hypophosphataemia following denosumab administration successfully managed using a calcimimetic agent. (PubMed, BMJ Case Rep) - "Evocalcet contributed to the normalised parathyroid hormone and phosphorus levels, allowing the discontinuation of phosphorus supplementation. This case highlights the complexity of managing electrolyte imbalances induced by bone-modifying agents, such as denosumab, underscoring the importance of monitoring bone metabolism markers and the potential effectiveness of evocalcet in managing drug-induced secondary hyperparathyroidism and hypophosphataemia."

Journal • Endocrine Disorders • Hepatology • Oncology • Osteosarcoma • Pancreatic Cancer • Renal Disease • Sarcoma • Secondary Hyperparathyroidism • Solid Tumor

Paradoxical cerebral embolism caused by patent foramen ovale in a patient with multiple endocrine neoplasia type 1 and severe primary hyperparathyroidism. (PubMed, BMJ Case Rep) - "Treatment was 24 mg of oral evocalcet and total parathyroidectomy with forearm autotransplantation, resulting in improved serum calcium and i-PTH levels. Finally, he underwent transcatheter PFO closure. We emphasise careful, etiological pursuit in young-onset stroke and the usefulness of genetic testing in differentiating hyperparathyroidism associated with mandibular tumours."

Journal • Cardiovascular • CNS Disorders • Endocrine Cancer • Endocrine Disorders • Ischemic stroke • Oncology • Solid Tumor • Transplantation

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

Heterogenous Origins of Calcium Homeostasis Disorders Arising from Five Heterozygous Calcium-Sensing Receptor Variants. (PubMed, J Clin Endocrinol Metab) - "While the molecular phenotypes exhibited by the five CaSR variants concord with the clinical phenotypes in individuals harboring them, CASR variant-induced calcium homeostasis disorders clearly arise from diverse molecular origins, and the effectiveness of calcimimetics in these disorders could differ depending on the specific variants."

Journal • Endocrine Disorders • Metabolic Disorders • CASR

Evocalcet demonstrates the improvement of the PTH-calcium setpoint and the suppression of parathyroid cell proliferation in a primary hyperparathyroidism model mouse (ASBMR 2024) - No abstract available

Preclinical • Endocrine Disorders • Renal Disease

Sporadic Parathyroid Carcinoma Treated With Lenvatinib, Exhibiting a Novel Somatic MEN1 Mutation. (PubMed, JCEM Case Rep) - "Although severe hand-foot syndrome necessitated dose reductions and treatment interruptions, sorafenib treatment managed hypercalcemia with evocalcet and denosumab. Lenvatinib, as second-line therapy, was effective against pleural metastases but caused thrombocytopenia and hematuria, leading to discontinuation and uncontrolled recurrence and metastasis progression. Our case highlights the need for further research on genomic profiling, molecular targets, and therapy response in PC."

Journal • Dermatology • Endocrine Cancer • Endocrine Disorders • Hematological Disorders • Metabolic Disorders • Oncology • Thrombocytopenia • KDR • MEN1

Pembrolizumab with external radiation therapy effectively controlled TMB-high unresectable recurrent parathyroid cancer: a case report with review of literature. (PubMed, Endocr J) - "He successfully achieved evocalcet and zoledronate withdrawal, and the PTH level improvement was continuously observed for 8 months at present, with only grade 2 subclinical hypothyroidism. A combination of PEM and RT is a promising treatment of unresectable TMB-high PC. Recent evidence on the immunomodulatory effect of RT provides the rationale for the combination of RT and PEM."

Journal • Review • Tumor mutational burden • Endocrine Cancer • Endocrine Disorders • Metabolic Disorders • Oncology • TMB

Effects of active vitamin D analogs and calcimimetic agents on PTH and bone mineral biomarkers in hemodialysis patients with SHPT: a network meta-analysis. (PubMed, Eur J Clin Pharmacol) - "The same kinds of agents perform similar efficacy on the level of PTH, serum calcium, phosphorus, and calcium-phosphorus product. Paricalcitol did not lead to more hypercalcemia than calcitriol. The calcium decrease induced by cinacalcet was not settled even by associating it with active vitamin D analogs. Cinacalcet and evocalcet were superior to calcitriol and paricacitol in reducing calcium-phosphorus product. Calcimimetics induced more gastrointestinal disorders than active vitamin D analogs, especially cinacalcet."

Biomarker • Clinical • Journal • Retrospective data • Endocrine Disorders • Gastroenterology • Gastrointestinal Disorder • Metabolic Disorders • Renal Disease • Secondary Hyperparathyroidism

Silicon-Rhodamine Functionalized Evocalcet Probes Potently and Selectively Label Calcium Sensing Receptors In Vitro, In Vivo, and Ex Vivo. (PubMed, ACS Pharmacol Transl Sci) - "In summary, functionalization of evocalcet by SiR led to the preparation of potent and specific fluorescent CaSR probes. EvoSiR4 is a versatile small-molecular probe that can be employed in CaSR-related biomedical analyses where antibodies are not applicable."

Journal • Preclinical • Asthma • Brain Cancer • Immunology • Inflammatory Bowel Disease • Oncology • Pulmonary Disease • Respiratory Diseases • CASR

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