Etelcalcetide (calcimimetic) for the Treatment of Secondary Hyperparathyroidism (SHPT), United States of America
Etelcalcetide (formerly AMG416), an intravenous injectable calcimimetic agent, is currently under development by Amgen for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) on haemodialysis.
Amgen submitted a new drug application (NDA) of etelcalcetide for the treatment of SHPT to the US Food and Drug Administration (FDA) in August 2015. The FDA accepted the NDA for review in November 2015, and also set the Prescription Drug User Fee Act (PDUFA) target action date of 24 August 2016.
Amgen submitted a marketing authorisation application (MAA) to the European Medicines Agency (EMA) for etelcalcetide for the treatment of SHPT in adult patients with CKD on haemodialysis therapy in September 2015. The MAA is currently under review by EMA. If approved by the FDA and EMA, etelcalcetide could become the first calcimimetic agent available for intravenous administration.
Secondary hyperparathyroidism (SHPT) is a chronic disease associated with the parathyroid gland and is characterised by excessive secretion of parathyroid hormone in response to hypocalcaemia (low blood calcium levels). The disorder normally develops in CKD patients.
It occurs in 90% of the patients with chronic renal failure on haemodialysis, and is usually referred to as renal hyperparathyroidism.
Hyperparathyroidism affects approximately two million people across the world, including roughly 350,000 people in Europe and 450,000 people in the US alone.
Etelcalcetide's mechanism of action
Etelcalcetide is an intravenously administered calcimimetic agent. The drug binds to the calcium-sensing receptors and activates them on the parathyroid gland, thereby decreasing the parathyroid hormone (PTH) secretion.
The drug is administered intravenously after every dialysis session.
The NDA for Etelcalcetide submitted to the FDA was based on three phase III randomised, placebo-controlled, double blind and double dummy clinical trials.
The head-to-head phase III clinical study was conducted for 26 weeks on 683 patients, and evaluated etelcalcetide's efficiency compared to cinacalcet.
The patients randomised with etelcalcetide received intravenous doses of etelcalceitide three times a week at the end of each dialysis session, and daily oral doses of placebo tablets.
The patients who were randomised with cinacalcet received daily oral doses of cinacalcet tablets and doses of placebo three times a week, at the end of each dialysis session.
The primary endpoint of the study was the proportion of patients with a greater than 30% reduction from baseline in mean PTH levels during weeks 20 and 27. The trial achieved the primary end point of groups of patients with a greater than 30% reduction in mean PTH from baseline. It also achieved the secondary end points, including greater than 50% reductions from baseline PTH during the efficacy assessment phase (EAP), and the mean number of days of vomiting or nausea a week in the first eight weeks.
The study results, presented at American Society of Nephrology (ASN), reported 92.9% treatment emergent adverse events (TEAEs) in patients with etelcalcetide, and 90% in patients with cinacalcet.
The TEAEs reported in at least 10% of the patients treated with etelcalcetide or cinacalcet included decreased blood calcium, nausea, vomiting, diarrhoea, hypocalcaemia, and cardiac failure.
The serious adverse events reported in etelcalcetide and cinacalcet-administered patients were 25.1% and 27.3% respectively, and fatal adverse events were 2.7 % and 1.8 % respectively.
The MAA application for etelcalcetide in Europe was also based on the results obtained from three phase III clinical studies. All the three studies met the primary endpoints. The clinical studies also included two pooled placebo-controlled trials in which more than 1,000 patients were evaluated in a head-to-head study comparing etelcalcetide with cinacalcet.