What is Evocac?

What is Evocalcet?

Evocalcet is a novel oral calcimimetic agent used to treat secondary hyperparathyroidism (SHPT) in chronic kidney disease patients on hemodialysis, offering equivalent efficacy to cinacalcet at lower doses with significantly fewer gastrointestinal adverse events. 1

Mechanism of Action

• Evocalcet targets the calcium-sensing receptor on parathyroid cells to suppress parathyroid hormone (PTH) secretion 1
• It reduces PTH levels without inducing hypercalcemia or hyperphosphatemia, similar to other calcimimetics 2
• The drug demonstrates efficient PTH suppression in animal models of chronic kidney disease induced by nephrectomy 2

Clinical Advantages Over Cinacalcet

Superior Gastrointestinal Tolerability

• Evocalcet produces significantly fewer upper gastrointestinal tract-related adverse events compared to cinacalcet 1
• In rat models, evocalcet showed no marked effects on gastric emptying, while cinacalcet induced significant delays 2
• Evocalcet demonstrated less induction of emesis compared to cinacalcet in common marmoset studies 2
• The reduced GI symptoms allow for adequate dosing without the compliance issues that plague cinacalcet therapy 1

Improved Pharmacokinetic Profile

• Evocalcet achieves equivalent efficacy to cinacalcet at lower clinical doses due to higher bioavailability 1, 2
• The improved bioavailability contributes to the reduced gastrointestinal tract symptoms 2
• Lower required doses provide a wider safety margin compared to cinacalcet 2

Fewer Drug Interactions

• Evocalcet shows no substantial direct inhibition of any cytochrome P450 (CYP) isozymes in liver microsome assays 2
• This contrasts with cinacalcet, which inhibits CYP2D6 and creates potential drug-drug interactions 2
• The lack of CYP inhibition provides a better safety profile for patients on multiple medications 2

Clinical Context: Secondary Hyperparathyroidism

• SHPT in chronic kidney disease is marked by elevated circulating PTH levels and increased risk of morbidity and mortality 1
• Calcimimetics have become popular in clinical settings as part of therapeutic combinations that commonly include vitamin D preparations 1
• Cinacalcet, while widely used, has a high incidence of upper GI tract-related adverse events resulting in insufficient dosage and poor long-term compliance 1

Common Pitfall to Avoid

• Do not assume evocalcet and cinacalcet are interchangeable at the same doses—evocalcet requires lower doses due to superior bioavailability 1, 2
• The improved tolerability profile does not eliminate the need to monitor for adverse events, though they occur less frequently 1