FDA approves Amgen's Parsabiv for secondary hyperparathyroidism
Amgen has announced that the FDA approved Parsabiv (etelcalcetide) for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis. Parsabiv is the first therapy approved for this condition in 12 years and the only calcimimetic that can be administered intravenously by the dialysis healthcare team three times a week at the end of the hemodialysis session.
"We are excited about today's approval of Parsabiv in the U.S. and the opportunity to provide patients and healthcare providers with a novel option to help treat a complex disease that affects a significant number of patients on hemodialysis," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Parsabiv not only has demonstrated strong efficacy in clinical trials, it also fills an unmet need by putting the delivery of the therapy in the hands of the health care professional."
Often occurring in patients in Stage 5 of CKD, secondary HPT refers to the excessive secretion of parathyroid hormone (PTH) by the parathyroid glands in response to decreased renal function and impaired mineral metabolism. Parsabiv binds to and activates the calcium-sensing receptor on the parathyroid gland, thereby causing decreases in PTH.
"As a physician who cares for patients with advanced chronic kidney disease, I understand the importance of achieving and maintaining simultaneous reductions in a number of complex lab values in the treatment of secondary HPT," said Geoffrey A. Block, M.D., nephrologist at Denver Nephrologists, PC, in Colorado. "The ability to provide my patients with an intravenous calcimimetic and help ensure they receive the therapy they need is a tremendous milestone in the management of this frequently undertreated chronic progressive disease."
Secondary HPT is a serious condition and the proportion of patients unable to reach recommended secondary HPT lab targets has more than doubled in the last five years. Sensipar (cinacalcet), the first FDA-approved calcimimetic, became an important treatment for patients with secondary HPT on dialysis based on its ability to reduce three important biochemical abnormalities (PTH, calcium, phosphorus). Parsabiv is a novel calcimimetic that can be delivered intravenously at the end the hemodialysis session and has been demonstrated to effectively reduce levels of PTH, corrected calcium and phosphate. These reductions were maintained for up to 78 weeks.
The approval of Parsabiv in the U.S. was largely based on data from two placebo-controlled phase III studies, both of which met their primary endpoints.
In the two 26-week, randomized, double-blind, placebo-controlled studies, an aggregate of 1,023 patients with moderate-to-severe secondary HPT (PTH greater than 400pg/mL) on hemodialysis were randomized to receive intravenous Parsabiv or placebo three times a week, at the end of their dialysis sessions in addition to standard of care that could include vitamin D and/or phosphate binders. The primary endpoint of both studies was the proportion of patients achieving greater than 30% reduction from baseline in PTH during the Efficacy Assessment Phase (EAP), defined as weeks 20 through 27. Secondary endpoints included the proportion of patients with PTH less than or equal to 300pg/mL during the EAP; and percent reductions in PTH, albumin-adjusted calcium (cCa), phosphate (P) and cCa x P during the EAP.
In a pooled analysis of the placebo-controlled studies, asymptomatic reductions in serum calcium and symptomatic hypocalcemia occurred more frequently in patients treated with Parsabiv compared to placebo (64% versus 10%, and 7% versus 0.2%, respectively). Other commonly reported adverse reactions were muscle spasms (12% versus 7%), diarrhea (11% versus 9%), nausea (11% versus 6%), vomiting (9% versus 5%), headache (8% versus 6%), and paresthesia/hypoesthesia (6% versus 1%).