Hypoparathyroidism treatment normalizes calcium for most adults in proof-of-concept trial
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Most adults with hypoparathyroidism had normalized calcium levels without needing a supplement after 3 months of taking a parathyroid hormone-1 receptor agonist, according to findings from phase 2a trial.
Amolyt Pharma announced that AZP-3601, a parathyroid hormone-1 receptor agonist, was effective and well tolerated by a cohort of adults with hypoparathyroidism, a parathyroid hormone deficiency that causes decreased levels of calcium and elevated phosphorus levels in the blood. Similar findings were previously reported in a prior cohort of patients.
“We are very pleased to see that the safety and efficacy data from cohort two validate the findings from the first cohort of patients in this study,” Mark Sumeray, MD, chief medical officer at Amolyt Pharma, said in a press release. “We observed success in the control of serum calcium and elimination of active vitamin D and oral calcium at levels that were even better than those achieved in cohort one. Mean urinary calcium excretion also rapidly normalized, particularly in patients with elevated urinary calcium at baseline, an important finding since more than 50% of patients with hypoparathyroidism have hypercalciuria. Bone biomarkers again provided evidence of a balanced and physiologic restoration of bone turnover without excess bone resorption, as also suggested by the bone mineral density data.”
In a phase 2a clinical proof-of-concept trial, 16 adults with hypoparathyroidism received daily subcutaneous injections of AZP-3601 for 4 weeks, followed by an 8-week extension phase. The starting dose was 10 mg and increased to 20 mg over 4 weeks. During the extension phase, the maximum allowed dose increased to 80 mg per day. Calcium and vitamin D supplementation were progressively removed during the study.
At the end of the trial, 93% of participants discontinued vitamin D and oral calcium supplementation. Mean albumin-adjusted serum calcium remained in the target range at 12 weeks, and 24-hour urinary excretion of calcium normalized for all but one participant. Bone turnover biomarkers increased at 2 weeks and remained in the mid-normal range through the end of the study. BMD also stabilized during the trial, according to the release.
The agent was well tolerated with no serious adverse events. Mild to moderate adverse events were consistent with prior studies, according to the release.
According to the press release, most participants required an increase in dose to 20 mg at week 2 of the trial, supporting the selection of 20 µg as the starting dose for an upcoming phase 3 trial. A phase 3 trial is planned to begin in 2023.
“We now have the clinical data needed to finalize our plans for a phase 3 trial of AZP-3601 and look forward to end-of-phase 2 discussions with health authorities with the goal of initiating the trial as soon as possible next year,” Sumeray said.
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