Drug for Secondary Hyperparathyroidism Meets Goals in Phase 3 Trials

AMG 416, a drug designed to treat secondary hyperparathyroidism (SHPT), has met its endpoints in a phase 3 clinical trial, the manufacturer Amgen in Thousand Oaks, CA, reported in July.

SHPT is common and can be severe in patients with chronic kidney disease (CKD) and in those receiving dialysis. At first, the parathyroid glands produce more parathyroid hormone in an effort to maintain normal serum calcium and phosphorus levels. However, as CKD progresses, SHPT can develop as the body shifts to a combination of abnormal levels of parathyroid hormone (PTH), calcium, and phosphorus.

The drug AMG 416 was part of Amgen’s acquisition of KAI Pharmaceuticals two years ago. The phase 3 study of 515 patients to evaluate AMG 416 (formerly known as velcalcetide) met its primary endpoint and all secondary endpoints with statistically significant results.

The primary endpoint was the proportion of patients with greater than 30 percent reduction from baseline in PTH levels during weeks 20 to 27 of the trial.

Of the patients taking the drug, 75.3 percent achieved a reduction of more than 30 percent from baseline in PTH, compared with just 9.6 percent in the placebo arm. Secondary endpoints included the percentage change from baseline during weeks 20 to 27 in serum phosphorus concentration (mean changes of −9.63 and −1.60 percent among patients in the study drug and placebo groups, respectively) and corrected calcium concentration (mean changes of −6.69 and 0.58 percent among patients in the AMG 416 and placebo groups, respectively).

“There is an important role for an effective calcimimetic [drug] that can be administered intravenously with hemodialysis to help treat this disease,” said Sean E. Harper, MD, executive vice president of research and development at Amgen. “We look forward to sharing results from a second placebo-controlled study later this year, and a head-to-head study evaluating AMG 416 compared to cinacalcet next year.”

Some adverse effects were reported by Amgen in the study group versus the placebo group, including blood calcium decrease (66.7 and 12.0 percent), diarrhea (14.3 and 10.0 percent), and muscle spasms (11.1 and 6.2 percent), respectively. Serious adverse events were reported in 24.6 and 27.4 percent of patients who received AMG 416 and placebo, respectively. For example, vomiting was reported in 7.5 and 3.1 percent of patients treated with AMG 416 and placebo, respectively. Symptoms of hypocalcemia were reported in 6.7 percent of patients who received AMG 416 versus no hypocalcemia in the placebo group.