The study met the primary endpoint of non-inferiority of etelcalcetide compared to cinacalcet, measured as the proportion of patients achieving a greater than 30 percent reduction from baseline in mean pre-dialysis serum intact parathyroid hormone (PTH) levels during the Efficacy Assessment Phase (EAP), defined as the period between weeks 20 and 27.
Etelcalcetide is a novel calcimimetic agent that suppresses the secretion of parathyroid hormone and is in clinical development for the treatment of SHPT in patients with CKD on hemodialysis. Etelcalcetide is administered intravenously three times per week at the end of each dialysis session. It acts by binding to and activating the calcium-sensing receptor on the parathyroid gland, thereby causing decreases in PTH. Sustained elevations in PTH are known to be associated with significant clinical consequences for patients with CKD.
In addition, etelcalcetide was superior to cinacalcet in the secondary endpoints of the proportion of patients achieving greater than 30 percent (68.2 percent versus 57.7 percent, p=0.004) and greater than 50 percent (52.4 percent versus 40.2 percent, p=0.001) reduction in PTH from baseline during the EAP. These differences were statistically significant. There was no difference between the treatment arms in the mean number of days of vomiting or nausea per week in the first eight weeks, another secondary endpoint.
"Treating SHPT in patients with chronic kidney disease on hemodialysis is associated with a number of challenges, and a high unmet need remains when it comes to the management of this complex disease," said
In the study presented at ASN, treatment-emergent adverse events (TEAEs) were reported in 92.9 and 90.0 percent of patients who received etelcalcetide and cinacalcet, respectively. TEAEs that were reported in greater than 10 percent of patients in either arm included (etelcalcetide versus cinacalcet, respectively): blood calcium decreased (68.9 and 59.8 percent), nausea (18.3 and 22.6 percent), vomiting (13.3 and 13.8 percent) and diarrhea (6.2 and 10.3 percent). TEAEs of hypocalcemia (symptomatic) were reported in 5.0 percent of patients who received etelcalcetide versus 2.3 percent in the cinacalcet group. Treatment-emergent events related to cardiac failure were reported in 3.0 percent of patients who received etelcalcetide versus 0.6 percent in the cinacalcet group. Serious adverse events were reported in 25.1 and 27.3 percent of patients who received etelcalcetide and cinacalcet, respectively. Fatal adverse events were reported in 2.7 percent for the etelcalcetide arm and 1.8 percent for the cinacalcet arm.
This was a randomized, active-controlled, double-blind, double-dummy study over 26 weeks that compared the efficacy and safety of etelcalcetide with cinacalcet for the treatment of SHPT in 683 patients with CKD receiving hemodialysis.
Patients randomized to treatment with etelcalcetide received intravenous (IV) doses of etelcalcetide three times per week at the end of each dialysis session and daily oral doses of placebo tablets. Subjects randomized to treatment with cinacalcet received daily oral doses of cinacalcet tablets and IV doses of placebo three times per week at the end of each dialysis session. Patients also received standard of care, which could include calcium supplements, vitamin D sterols and phosphate binders, if prescribed by the individual physician.
The primary endpoint was the proportion of patients with greater than 30 percent reduction from baseline in mean PTH levels during weeks 20 and 27, with the objective of demonstrating non-inferiority of etelcalcetide to cinacalcet.
Key and other secondary endpoints included the achievement of a greater than 30 percent and greater than 50 percent reductions from baseline PTH during the EAP, and the mean number of days of vomiting or nausea per week in the first eight weeks. Nausea or vomiting days were collected by the Nausea/Vomiting Symptom Assessment (NVSA) patient assessment daily questionnaires.
About Secondary Hyperparathyroidism
SHPT is a common and serious condition that is often progressive among patients with CKD, and it affects many of the approximately two million people throughout the world who are receiving dialysis, including 450,000 people in the U.S. The disorder develops early in the course of CKD and usually manifests as increased levels of parathyroid hormone (PTH) as a result of increased production from the parathyroid glands (four small glands in the neck).
Patients with end stage renal disease who require maintenance dialysis often have substantial elevations of PTH that are commonly associated with abnormal calcium and phosphorus levels and an increased risk of significant clinical consequences.
About Etelcalcetide (formerly AMG 416)
Etelcalcetide is a novel calcimimetic agent in clinical development for the treatment of SHPT in CKD patients on hemodialysis that is administered intravenously at the end of the dialysis session. Etelcalcetide binds to and activates the calcium-sensing receptor on the parathyroid gland, thereby decreasing PTH levels.
About Sensipar® (cinacalcet)
Sensipar® (cinacalcet) is the first oral calcimimetic agent approved by the
Important Safety Information
Sensipar® (cinacalcet) treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal range (8.4 mg/dL).
Sensipar® lowers serum calcium; therefore, it is important that patients are carefully monitored for the occurrence of hypocalcemia. Life threatening events and fatal outcomes associated with hypocalcemia have been reported in patients treated with Sensipar®, including pediatric patients. Decreases in serum calcium can prolong the QT interval, potentially resulting in ventricular arrhythmia. Cases of QT prolongation and ventricular arrhythmia secondary to hypocalcemia have been reported in patients treated with Sensipar®.
Significant reductions in calcium may lower the threshold for seizures. Patients, particularly those with a history of seizure disorder, should be carefully monitored for the occurrence of low serum calcium or symptoms of hypocalcemia.
In Sensipar® postmarketing use, isolated, idiosyncratic cases of hypotension, worsening heart failure, and/or arrhythmia were reported in patients with impaired cardiac function. The causal relationship to Sensipar® therapy could not be completely excluded and may be mediated by reductions in serum calcium levels.
Adynamic bone disease may develop if intact parathyroid hormone (iPTH) levels are suppressed below 100 pg/mL. Patients with moderate to severe hepatic impairment should be monitored throughout treatment with Sensipar®, as cinacalcet exposure assessed by area under the curve (AUC) was higher than in patients with normal hepatic function. Patients with secondary HPT: Serum calcium and serum phosphorus should be measured within 1 week and PTH should be measured 1 to 4 weeks after initiation or dose adjustment of Sensipar®. Once the maintenance dose has been established, serum calcium and serum phosphorus should be measured approximately monthly, and PTH every 1 to 3 months. Patients with primary HPT or parathyroid carcinoma: Serum calcium should be measured within 1 week after initiation or dose adjustment of Sensipar®. Once maintenance dose levels have been established, serum calcium should be measured every 2 months. In clinical trials of patients with secondary HPT comparing Sensipar® to placebo, the most commonly reported side effects were nausea (31 percent vs. 19 percent), vomiting (27 percent vs. 15 percent), and diarrhea (21 percent vs. 20 percent). In clinical trials of patients with primary HPT and parathyroid carcinoma treated with Sensipar®, the most commonly reported side effects were nausea (63 percent), vomiting (46 percent), and paresthesia (20 percent).
Please see Full Prescribing Information.
This news release contains forward-looking statements that are based on the current expectations and beliefs of
No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us and our partners to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products after they are on the market. Our business may be impacted by government investigations, litigation and product liability claims. If we fail to meet the compliance obligations in the corporate integrity agreement between us and the U.S. government, we could become subject to significant sanctions. We depend on third parties for a significant portion of our manufacturing capacity for the supply of certain of our current and future products and limits on supply may constrain sales of certain of our current products and product candidate development.
In addition, sales of our products (including products of our wholly-owned subsidiaries) are affected by the reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment as well as U.S. legislation affecting pharmaceutical pricing and reimbursement. Government and others' regulations and reimbursement policies may affect the development, usage and pricing of our products. In addition, we compete with other companies with respect to some of our marketed products as well as for the discovery and development of new products. We believe that some of our newer products, product candidates or new indications for existing products, may face competition when and as they are approved and marketed. Our products may compete against products that have lower prices, established reimbursement, superior performance, are easier to administer, or that are otherwise competitive with our products. In addition, while we and our partners routinely obtain patents for products and technology, the protection of our products offered by patents and patent applications may be challenged, invalidated or circumvented by our or our partners' competitors and there can be no guarantee of our or our partners' ability to obtain or maintain patent protection for our products or product candidates. We cannot guarantee that we will be able to produce commercially successful products or maintain the commercial success of our existing products. Our stock price may be affected by actual or perceived market opportunity, competitive position, and success or failure of our products or product candidates. Further, the discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to integrate the operations of companies we have acquired may not be successful. We may experience difficulties, delays or unexpected costs and not achieve anticipated benefits and savings from our restructuring plan. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase common stock.
The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by the
To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/amgen-presents-detailed-data-comparing-etelcalcetide-with-cinacalcet-in-patients-with-secondary-hyperparathyroidism-receiving-hemodialysis-300174374.html