Amolyt Reports Positive Results from Second Patient Cohort in Phase 2a Hypoparathyroidism Trial

Amolyt Pharma reported positive results from the second patient cohort in its phase 2a clinical proof-of-concept trial of AZP-3601, its experimental therapy for the rare endocrine condition hypoparathyroidism.

Consistent with the findings from Cohort 1, in the full data set from the phase 2a study, AZP-3601 was well-tolerated, and daily administration enabled 93 percent of patients to discontinue standard of care therapy (calcium and vitamin D supplementation) while mean serum calcium was maintained within the target range. Mean urinary calcium excretion was rapidly normalized and bone biomarkers increased in line with a resumption of a normalized physiological level of bone turnover.

AZP-3601 was well tolerated with no serious adverse events. There were only mild to moderate adverse events, consistent with prior studies.

Hypoparathyroidism is defined by a deficiency of parathyroid hormone (PTH) that results in decreased calcium and elevated phosphorus levels in the blood. Approximately 80 percent of the estimated 80,000 people in the United States and 110,000 in the European Union with hypoparathyroidism are women. Despite available treatments, patients experience persistent, life-altering symptoms and often develop complications and comorbidities that diminish quality of life and create segments of the patient population with specific clinical needs. Clinical manifestations of hypoparathyroidism impact many tissues and organ systems, in particular, the kidneys and bone. Some 17 percent of patients with hypoparathyroidism have osteopenia or osteoporosis and 53 percent are peri- or postmenopausal women with an increased risk of developing osteoporosis. Approximately 26 percent of patients with hypoparathyroidism have chronic kidney disease or failure, highlighting the importance of reducing urinary calcium excretion as a key treatment goal.

AZP-3601 is an experimental therapeutic peptide designed to target a specific conformation of the parathyroid hormone receptor to safely produce sustained and stable levels of calcium in the blood and thereby manage the symptoms of hypoparathyroidism, and to limit urine calcium excretion by restoring calcium reabsorption by the kidney, with the goal of consequently preventing chronic kidney disease. In addition to its unique receptor profile, AZP-3601 is also designed to have a short half-life to potentially preserve bone integrity, an important benefit, since the majority of patients are peri- and postmenopausal women with an increased risk of developing osteoporosis.

The lower starting dose (10µg) used in this cohort required an early up-titration to 20 µg in most patients after two weeks to allow discontinuation of oral vitamin D and calcium supplementation, supporting the selection of 20μg as the starting dose for the phase 3 trial.

In this second cohort, 16 patients with hypoparathyroidism received daily subcutaneous injections of AZP-3601 during a four-week main treatment period, followed by an eight-week extension phase. AZP-3601 was initiated at a starting dose of 10 µg while calcium and vitamin D supplementation were progressively removed. If necessary, the dose could be increased to 20 µg after two weeks of treatment until the end of the main period. During the extension phase further individual titration of AZP-3601 was allowed up to a maximum dose of 80 µg per day.

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. Data from both cohorts provide further support for the target profile of AZP-3601 and for the planned initiation of the phase 3 trial next year.

“Over recent weeks, as we have discussed the emerging efficacy and safety profile of this novel PTH1 receptor agonist with experts in the management of hypoparathyroidism,” said  Thierry Abribat, founder and CEO of Amolyt Pharma, “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.”

Author: Rare Daily Staff