Amgen has announced that a second placebo-controlled, phase III study evaluating AMG 416 for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD), receiving hemodialysis, met its primary and all secondary endpoints.
The primary endpoint was the proportion of patients with >30% reduction from baseline in parathyroid hormone (PTH) levels during an Efficacy Assessment Phase (EAP) defined as the period between weeks 20 and 27. These results follow the recent announcement of positive data from a prior placebo-controlled, phase III study of AMG 416, which was similar in design and size.
In the AMG 416 group, 74% of patients achieved a >30% reduction from baseline in PTH compared with 8.3% in the placebo arm, a statistically significant result. Secondary endpoints included the percent change from baseline during the EAP in serum phosphorus (P) concentration (mean changes of -7.71% and -1.31% among patients in the AMG 416 and placebo arms, respectively) and corrected calcium (cCa) concentration (mean changes of -7.29% and 1.18% among patients in the AMG 416 and placebo arms, respectively). Both of these secondary endpoint results were statistically significant.
"The results from this second phase III study help to confirm that AMG 416 could become an important new treatment option for dialysis patients with secondary hyperparathyroidism," said Sean E. Harper, M.D., executive vice president of R&D at Amgen. "Despite the variety of options available for the treatment of this disease, an unmet need remains for an intravenous therapy that can be administered along with hemodialysis.”
Treatment-emergent adverse events (TEAEs) were reported in 91.6% and 78.7% of patients who received AMG 416 and placebo, respectively. TEAEs that were reported in >10% of patients who received AMG 416 included (AMG 416 v. placebo, respectively): blood calcium decreased (61% and 8.3%), nausea (12.4% and 5.1%), muscle spasms (12% and 7.1%) and vomiting (10.4% and 7.1%). TEAEs of hypocalcemia (symptomatic) were reported in 7.2% of patients who received AMG 416 versus 0.4% in the placebo group. Serious adverse events (SAEs) were reported in 27.1% and 30.7% of patients who received AMG 416 and placebo, respectively.
This was a 26-week, randomized, double-blind, placebo-controlled study (study number 20120229) that evaluated the efficacy and safety of AMG 416 for the treatment of SHPT in 508 patients with CKD receiving hemodialysis. Patients received AMG 416 or placebo three times per week by intravenous injection with each hemodialysis treatment. Doses ranged from a minimum of 2.5mg to a maximum of 15mg. Patients also received standard of care, which could include calcium supplements, vitamin D sterols and phosphate binders, if prescribed by the individual physician.
Secondary endpoints included the proportion of patients with PTH <= 300pg/mL during the EAP and the percent change from baseline during the EAP in values for PTH, serum cCa, corrected calcium-phosphorus product (cCa x P) and P.