Amolyt’s AZP-3601 Safely Normalizes Calcium Levels in Trial

Most participants discontinued standard calcium and vitamin D supplementation

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Treatment with AZP-3601, Amolyt Pharma’s experimental therapy for hypoparathyroidism, safely brought calcium levels to within normal ranges in the first group of patients in a Phase 2 clinical trial, the company has announced.

Most of the trial participants were able to discontinue standard treatment with calcium and vitamin D supplements, and markers of bone health remained within normal ranges.

“We are very pleased with the compelling results from the first patient cohort of this ongoing trial,” Mark Sumeray, MD, Amolyt’s chief medical officer, said in a press release.

“We look forward to results from Cohort 2, which will inform the design of a Phase 3 trial as we work to advance this promising therapeutic peptide through an efficient late-stage development plan,” Sumeray added.

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What is AZP-3601?

Hypoparathyroidism is characterized by low levels of parathyroid hormone (PTH), which regulates levels of calcium, vitamin D, and phosphorus in the body. AZP-3601 is designed to mimic the biological activity of PTH to normalize these levels. The experimental therapy was also designed to be rapidly excreted from the body, as too-high PTH activity can interfere with bone health.

A previous Phase 1 study in healthy volunteers showed the experimental treatment was generally well-tolerated and that it could increase levels of calcium in the blood.

In this Phase 2 trial, people with hypoparathyroidism first underwent a titration period of up to eight weeks, where they were given standard calcium and vitamin D supplements at various doses until a dose regimen was identified that could maintain serum (blood) calcium levels between 7.8 and 9 mg/dL.

Once blood calcium levels were stable, participants started treatment with AZP-3601, given once per day via subcutaneous (under-the-skin) injection. The starting dose of AZP-3601 was 20 micrograms, and the dose could be adjusted up to 60 micrograms based on treatment response.

Participants were given AZP-3601 for 28 days, while simultaneously taking reduced doses of supplements. By the end of the study, 90% of patients were no longer on vitamin D supplements, and 80% were no longer on calcium supplements — while serum calcium levels remained in the target range.

People with hypoparathyroidism often secrete excess amounts of calcium in the urine (hypercalciuria), which can cause kidney damage. In all patients with high urine calcium secretion at the study’s start, treatment with AZP-3601 rapidly brought urine calcium levels down to within the normal range, according to Amolyt.

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Two markers of bone turnover (P1NP and CTX) increased somewhat in the first two weeks of AZP-3601, but remained within normal ranges for the duration of the study. Bone turnover refers to the process of bone resorption followed by replacement with new bone.

“The data demonstrate that the mechanism of action of AZP-3601 translates into important potential clinical benefits for patients with hypoparathyroidism, in particular those with or at risk of developing hypercalciuria, osteopenia or osteoporosis [bone diseases], who represent the majority of patients with this disease,” said Sumeray.

The experimental treatment was generally well-tolerated. All reported adverse events (side effects) were mild or moderate in severity.

“With AZP-3601, our key underlying assumption is that intermittent administration of this PTH analog … would induce a long-acting effect on serum Ca [calcium], mainly through a potent and sustained effect on Ca reabsorption in the kidney, while stimulating resumption of normal bone metabolism, thus preserving bone minerality,” said Thierry Abribat, PhD, founder and CEO of Amolyt. “These data support this assumption, outlining a potentially new clinical profile, which we believe is ideally suited to address the needs of patients with hypoparathyroidism.”