Date: 2017-01-10
Type of information: Publication of results in a medical journal
phase: 3
Announcement: publication of results in The Journal of the American Medical Directors Association (JAMA)
Company: Amgen (USA - CA)
Product: Parsabiv™ (etelcalcetide - AMG 416)
Action
mechanism: calcimimetic agent. AMG 416 is a novel calcimimetic agent developed for the treatment of SHPT that is administed intravenously in patients with CKD who are receiving hemodialysis. AMG 416 binds to and activates the calcium-sensing receptor on the parathyroid gland, thereby causing decreases in PTH.
Disease: secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) on hemodialysis
Therapeutic area: Kidney diseases - Metabolic diseases - Renal diseases
Country:
Trial
details: In the two 26-week, multicenter, randomized, double-blind, placebo-controlled studies, an aggregate of 1,023 adult patients with sHPT (PTH greater than 400 pg/mL) on hemodialysis were randomized to receive intravenous Parsabiv or placebo three times a week at the end of their dialysis sessions. All patients, regardless of treatment assignment, received standard of care with phosphate binders and calcitriol or active vitamin D analogs, as prescribed. The Phase 3 randomized, double-blind, double-dummy, active controlled trial was designed to compare the efficacy and safety of intravenous Parsabiv and oral Sensipar in 683 adult sHPT patients (340 randomized to Parsabiv and 343 to Sensipar) on hemodialysis. The patients were from 164 sites in the U.S., Canada , Europe , Russia and New Zealand . Patients receiving maintenance hemodialysis three times per week with sHPT (pre-dialysis serum PTH>500 pg/mL) on stable doses of calcium supplements or phosphate binders and calcitriol or active vitamin D analogs, if prescribed, with albumin-corrected serum calcium >8.3 mg/dL were eligible for participation. A total of 1,706 patients were enrolled across the three trials to evaluate the safety and efficacy of Parsabiv™ in the treatment of adult sHPT patients on hemodialysis.
The primary endpoint of the studies was the proportion of patients achieving greater than 30 percent reduction in PTH during the EAP. Secondary endpoints included the proportion of patients with PTH less than or equal to 300 pg/mL during the EAP, and percent change from baseline during the EAP for PTH, serum calcium, phosphate and calcium phosphate product (Ca x P).The two placebo-controlled trials were double-blind studies in a total of 1,023 adult patients with sHPT on hemodialysis. The patients were randomized to receive intravenous Parsabiv or placebo three times a week at the end of their dialysis sessions, and both arms also received standard of care as prescribed by the treating physician.
Patients who were randomized to treatment with Parsabiv/oral placebo received intravenous doses three times a week at the end of their dialysis sessions and daily oral doses of placebo tablets. Patients in the comparison group received daily oral doses of Sensipar tablets and intravenous doses of placebo three times a week at the end of their dialysis sessions. The primary endpoint was the proportion of patients with greater than 30 percent reduction from baseline in mean serum PTH during the EAP (weeks 20-27). Key secondary endpoints included the proportion of patients with greater than 50 percent and greater than 30 percent reduction in PTH, and the mean weekly days of self-reported nausea and vomiting over the first eight weeks.
Latest
news: * On January 10, 2017, Amgen announced the Journal of the American Medical Association (JAMA) publication of findings from three Phase 3 studies of Parsabiv™ (etelcalcetide), an investigational intravenous calcimimetic agent in the U.S. The studies evaluated Parsabiv™ in more than 1,700 adults with secondary hyperparathyroidism (sHPT) on hemodialysis and showed that the drug produced statistically significant and clinically meaningful reductions in serum parathyroid hormone (PTH) levels, a key marker of sHPT. sHPT is a chronic and serious condition that is often progressive among patients with chronic kidney disease (CKD) and is associated with significant clinical consequences.1
In two parallel Phase 3 randomized placebo-controlled studies in CKD patients with sHPT on hemodialysis, Parsabiv™ met the primary endpoint and significantly reduced serum PTH by more than 30 percent in 74.7 percent of patients compared to 8.9 percent given placebo. In addition, a head-to-head study comparing Parsabiv™ to oral Sensipar® (cinacalcet) also met its primary endpoint. This head-to-head study showed Parsabiv was non-inferior to oral Sensipar in the proportion of patients achieving 30 percent or greater serum PTH reduction. Further, Parsabiv™ was superior to Sensipar for the secondary endpoints of proportion of patients achieving greater than 30 percent and greater than 50 percent reduction in mean PTH during the Efficacy Assessment Phase (EAP) compared with baseline.
A total of 1,706 patients were enrolled across the three trials to evaluate the safety and efficacy of Parsabiv™ in the treatment of adult sHPT patients on hemodialysis.
The two placebo-controlled trials were double-blind studies in a total of 1,023 adult patients with sHPT on hemodialysis. The patients were randomized to receive intravenous Parsabiv or placebo three times a week at the end of their dialysis sessions, and both arms also received standard of care as prescribed by the treating physician. Both of the trials showed that, by weeks 20-27, significantly more Parsabiv patients compared to placebo patients achieved: Greater than a 30 percent reduction from baseline in mean serum PTH during weeks 20-27: 74.0 percent versus 8.3 percent (p<0.001) and 75.3 percent versus 9.6 percent (p<0.001)
Serum PTH levels of 300 pg/mL or less: 49.6 percent versus 5.1 percent (p<0.001) and 53.3 percent versus 4.6 percent (p<0.001)
The most common treatment-emergent adverse events (TEAEs) in the placebo-controlled studies that occurred at a rate greater than 10 percent in the Parsabiv group, and more frequently than in the placebo group in either of the studies, were blood calcium decreases (asymptomatic reductions in serum calcium), muscle spasms, diarrhea, nausea and vomiting. The overall rates of fatal adverse events, serious adverse events and adverse events leading to discontinuation of investigational product were similar in the Parsabiv and placebo groups.
The head-to-head study against Sensipar included 683 patients with sHPT on hemodialysis, and found Parsabiv resulted in a higher proportion of patients reaching at least a 30 percent reduction in mean serum PTH during weeks 20-27 compared to baseline: 68.2 percent versus 57.7 percent, respectively (p=0.004). Significantly more Parsabiv patients also achieved greater than a 50 percent reduction from baseline in mean serum PTH during weeks 20-27: 52.4 percent versus 40.2 percent, respectively (p=0.001). There was no statistically significant difference between the two groups in the mean number of days of vomiting or nausea per week in the first eight weeks, a secondary endpoint. TEAEs that were reported in greater than 10 percent of patients in either arm included blood calcium decreases, nausea, vomiting and diarrhea. TEAEs of hypocalcemia (symptomatic) were reported in 5.0 percent of patients who received Parsabiv versus 2.3 percent in the Sensipar group.
