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

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

Pharmacokinetics, Pharmacodynamics, and Safety of Evocalcet (KHK7580), a Novel Calcimimetic Agent: An Open-Label, Single- and Multiple-Dose, Phase I Trial in Healthy Chinese Subjects. (PubMed, Drug Des Devel Ther) - "No serious or severe TEAE occurred. In healthy Chinese subjects, evocalcet demonstrated dose-dependent PK and PD properties and was well-tolerated."

Clinical • P1 data • PK/PD data • Endocrine Disorders • Hypoparathyroidism • Ophthalmology • Renal Disease

Comparison of the Oral Calcimimetics Evocalcet and Cinacalcet in East Asian Patients on Hemodialysis with Secondary Hyperparathyroidism. (PubMed, Kidney Int Rep) - "Gastrointestinal adverse events (AEs) were significantly less frequent with evocalcet compared with cinacalcet (33.5% vs. 50.5%, P = 0.001), whereas the incidence of hypocalcemia did not differ. Evocalcet might be a better alternative to cinacalcet for East Asian patients on hemodialysis with SHPT."

Clinical • Journal • Endocrine Disorders • Gastrointestinal Disorder • 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

Effects of evocalcet on parathyroid calcium-sensing receptor and vitamin D receptor expression in uremic rats. (PubMed, FASEB J) - "We examined the effects of Evo and cinacalcet (Cina) on CaSR and VDR expression in 5/6 nephrectomized Sprague-Dawley rats fed a high-phosphorus diet for 4 weeks to develop secondary hyperparathyroidism (SHPT). A similar trend was observed for VDR expression. These results indicate that Evo and Cina treatment can increase parathyroid CaSR and VDR expression in uremic rats with SHPT, which could provide better control of mineral and bone disorder markers."

Journal • Preclinical • Endocrine Disorders • Metabolic Disorders • Nephrology • Orthopedics • Renal Disease • Secondary Hyperparathyroidism • CASR • VDR

Evocalcet rescues secondary hyperparathyroidism-driven cortical porosity in chronic kidney disease male rats. (PubMed, Endocrinology) - "Cell death of cultured osteocytes increased in a Pi concentration-dependent manner, and PTH administration rapidly elevated Pit1 expression and enhanced osteocytic death, indicating the possibility that the highly-concentrated serum PTH and Pi cause severe peri-lacunar osteolysis and osteocytic cell death. It is likely therefore that evocalcet not only decreases serum PTH but also reduces the exacerbation combined with PTH and Pi to the demineralization of osteocytic lacunae and osteocytic cell death, thereby protecting cortical porosity in CKD-SHPT rats."

Journal • Preclinical • Chronic Kidney Disease • Endocrine Disorders • Nephrology • Renal Disease • Secondary Hyperparathyroidism

Parathyroid carcinoma with pancreatitis causing hypercalcaemic emergency treated with extracorporeal membrane oxygenation-assisted parathyroid resection. (PubMed, Endocrinol Diabetes Metab Case Rep) - "Calcitonin, followed by denosumab, calcimimetic agents, and continuous hemodiafiltration were administered...General therapy for hypercalcaemia including aggressive saline dehydration, administration of furosemide, calcitonin, zoledronic acid, and evocalcet, and dialysis is sometimes ineffective for parathyroid carcinoma. Therefore, careful planning of therapy in case of exacerbation is important. During an emergency, rapid surgical treatment despite high calcium level is the best potential therapeutic strategy."

Journal • Endocrine Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatitis • Solid Tumor • CRP • MB

Effect of early dose increase of evocalcet for intractable hypercalcemia caused by parathyroid carcinoma. (PubMed, Endocrinol Diabetes Metab Case Rep) - "PC has a high recurrence rate. En-block excision is necessary when PC is suspected."

Journal • Endocrine Cancer • Endocrine Disorders • Gastrointestinal Disorder • Metabolic Disorders • Nephrology • Oncology • Psychiatry • Rare Diseases • Renal Disease

Combined treatment by burosumab and a calcimimetic can ameliorate hypophosphatemia due to excessive actions of FGF23 and PTH in adult XLH with tertiary hyperparathyroidism: A case report. (PubMed, Front Endocrinol (Lausanne)) - "A calcimimetic, evocalcet, increased the serum phosphate level and TmP/GFR. Therefore, it is important to evaluate the presence of secondary-tertiary hyperparathyroidism in patients whose serum phosphate level does not increase with burosumab treatment."

Journal • Endocrine Disorders • Renal Disease • FGF23

ORCHESTRA Trial: Head-to-Head Comparison of Oral Calcimimetics Evocalcet and Cinacalcet in East Asian Hemodialysis Patients With Secondary Hyperparathyroidism (KIDNEY WEEK 2022) - P3 | "Conclusion In East Asian HD patients with SHPT, the efficacy of evocalcet in reducing serum iPTH is non-inferior to cinacalcet, and evocalcet showed significantly reduced GI side effects compared with cinacalcet. Evocalcet therefore presents a preferable treatment alternative to cinacalcet for SHPT."

Clinical • Head-to-Head • Endocrine Disorders • Gastrointestinal Disorder • Renal Disease • Secondary Hyperparathyroidism