AZP-3601’s Efficacy Data Support Phase 3 Trial Next Year, Amolyt Says

Daily treatment normalizes calcium levels in 2nd patient group in a Phase 2a trial

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Daily treatment with AZP-3601, Amolyt Pharma’s experimental therapy for hypoparathyroidism, safely and effectively normalizes calcium levels in people with the disease, according to data from the second group of patients in a proof-of-concept Phase 2a clinical trial.

Most participants stopped calcium and vitamin D supplements, which is the standard care, and markers of bone mineral density remained stable, including in patients with osteopenia, a condition marked by lower-than-normal bone density which makes bones weaker.

“We are very pleased to see that the safety and efficacy data from Cohort [group] 2 validate the findings from the first cohort of patients in this study,” Mark Sumeray, MD, Amolyt’s chief medical officer, said in a company press release.

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Amolyt seeks to launch Phase 3 testing of AZP-3601 ‘as soon as possible next year’

According to Amolyt, the results from both groups support the testing of AZP-3601 in a Phase 3 trial, which the company expects to launch next year.

“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 added.

Hypoparathyroidism is marked by low levels of the parathyroid hormone (PTH) that causes a deficiency in calcium and vitamin D, and a rise in phosphorus in the body. Calcium deficiency is associated with a range of symptoms, including numbness in the fingers and toes to seizures and pain.

AZP-3601 was designed to mimic the function of PTH and normalize these levels, while being eliminated from the body quickly, since excessive PTH can have detrimental bone effects.

Following promising results in a Phase 1 trial of healthy volunteers, the therapy’s safety and effectiveness was assessed in adults with hypoparathyroidism in a Phase 2 trial.

The first group of patients (12 people) received under-the-skin injections of 20 micrograms of AZP-3601, once a day for four weeks, while calcium and vitamin D supplementation was progressively discontinued.

This was followed by a two-month extension period, where individual dose increases up to 60 micrograms were allowed for patients to achieve calcium levels within the target range.

Results from this group of patients showed that the therapy safely normalized calcium levels and allowed more than 80% of patients to discontinue standard supplement therapy.

AZP-3601 treatment was also associated with a normalization of urine calcium levels, which are often elevated in hypoparathyroidism patients on standard supplement therapy and can cause kidney damage.

AZP-3601 continues to show efficacy in 16 patients in trial

Newly announced data concerned the 16 patients enrolled in the second group of the trial. They were given once-a-day injections of AZP-3601 for one month, starting at a dose of 10 micrograms that could be increased to 20 micrograms after two weeks of treatment.

In a two-month extension period, patients were allowed to adjust their daily therapy dose to a maximum of 80 micrograms.

“These adjustments to the dosing protocol for Cohort 2 were implemented to allow a comprehensive dose range evaluation and to inform the design and dose selection for a Phase 3 study,” Amolyt stated in the release.

The new data showed that by the end of the three-month treatment, 93% of patients (13 of 14 patients) had stopped taking both vitamin D and calcium supplements, while blood calcium levels remained within the target range.

“We observed success in the control of [blood] calcium and elimination of active vitamin D and oral calcium at levels that were even better than those achieved in Cohort 1,” Sumeray said.

AZP-3601 also induced a rapid normalization of 24-hour urinary calcium in all but one patient, including those with high urine calcium levels at the study’s start. This is “an important finding since more than 50% of patients with hypoparathyroidism have hypercalciuria [high urine calcium levels],” Sumeray said.

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Also, the levels of P1NP and CTX, two markers of bone turnover, increased after two weeks of treatment, and remained within normal levels throughout the study, similar to that seen in the first group of patients. Bone turnover is the process of bone resorption followed by replacement with new bone.

“Bone biomarkers again provided evidence of a balanced and physiologic restoration of bone turnover without excess bone resorption, as also suggested by the BMD [bone mineral density] data,” Sumeray said.

In agreement with the safety profile reported in prior studies, AZP-3601 was generally well-tolerated, with no serious adverse events, and reported adverse events were mild to moderate in severity.

Since the majority of patients required a 20-microgram dose to allow them to discontinue calcium and vitamin D supplements, this would be the selected starting dose for the upcoming Phase 3 trial.

“The data are very encouraging for the future development of AZP-3601,” said Thierry Abribat, PhD, founder and CEO of Amolyt.

“Over recent weeks, as we have discussed the emerging efficacy and safety profile of this [new therapy] with experts in the management of hypoparathyroidism, it has become increasingly clear that the observed rapid normalization of mean urinary calcium excretion combined with balanced resumption of bone turnover supports the potential of AZP-3601 to uniquely address the key treatment goals for these patients,” Abribat added.

“We are excited to move forward to our Phase 3 study.”