FDA Grants Fast Track Designation to Eneboparatide for Treatment of Patients With Hypoparathyroidism

Author(s):

Gillian McGovern, Assistant Editor

Currently, the treatment is being evaluated in the phase 3 CALYPSO study to further prove the safety and efficacy in patients with hypoparathyroidism.

The FDA granted a fast track designation to eneboparatide (AZP-3601; Amolyt Pharma) for the treatment of patients with hypoparathyroidism. The treatment had demonstrated positive effects in a phase 2 clinical trial, and it is continuing to be evaluated in the phase 3 trial, CALYPSO (NCT05778071).¹

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Eneboparatide is an investigational therapeutic peptide designed to bind to a specific conformation of the parathyroid hormone (PTH) receptor to produce stable and sustained levels of calcium in the blood, which manages symptoms of hypoparathyroidism. Additionally, the drug also limits the amount of calcium excreted through urine by restoring the calcium reabsorption by the kidney, subsequently preventing progressive decline in kidney function and the development of chronic kidney disease. Eneboparatide also has a short half-life to help preserve bone integrity, which is important for patients with hypoparathyroidism because most are peri- and postmenopausal women who have an increased risk of developing osteoporosis.¹

“We believe FDA’s granting of fast track designation to eneboparatide reflects the agency’s recognition of the significant unmet needs that persist among patients suffering from hypoparathyroidism,” said Thierry Abribat, PhD, founder and CEO of Amolyt Pharma, in a press release. “We look forward to maintaining a constructive dialog with the agency as we work to bring new hope to patients suffering from this rare but challenging endocrine disorder as efficiently as possible.”¹

About the Trial

Trial Name: Evaluation of the Safety and Efficacy of Eneboparatide (AZP-3601) in Patients With Chronic Hypoparathyroidism (CALYPSO)

ClinicalTrials.gov ID: NCT05778071

Sponsor: Amolyt Pharma

Completion Date (Estimated): June 2025

CALYPSO is a multicenter, randomized, placebo-controlled, double-blind phase 3 study designed to evaluate the efficacy and safety of eneboparatide in patients with chronic hypoparathyroidism. A total of 165 patients were enrolled and treated with standard of care, then were randomly assigned to receive eneboparatide (starting dose 20 mcg, concentration of 250 mcg/mL or 500 mcg/mL) or placebo, administered subcutaneously once per day. Following the initial 24-week placebo-controlled period, the entire patient population—regardless of them receiving eneboparatide or placebo—will be treated with eneboparatide in an open-label extension phase for an additional 28 weeks.^1,2

The study’s primary end point is the proportion of patients who achieve an album-adjusted serum calcium (ADsCa) within the normal range as well as independence from standard of care at 24 weeks following initial treatment. Key secondary end points include the normalization of 24-hour urinary calcium in patients who have hypercalciuria at baseline and the assessment of outcomes reported by patients that reflect physical and cognitive function-related symptoms that impact quality of life. Additional exploratory end points assess the bone quality and quantity using DXA scanning and high resolution peripheral quantitative CT scanning.^1,2

The prior open-label phase 2 trial studied the efficacy, safety, and tolerability of eneboparatide in patients with hypoparathyroidism. A total of 28 patients were enrolled into 2 consecutive cohorts (cohort 1: n = 12; cohort 2: n = 16), with patients receiving daily subcutaneous injections of eneboparatide of 20 µg (cohort 1) or 10 µg (cohort 2). Additionally, conventional therapy was progressively removed allowing eneboparatide to be titrated up to 60 µg and 80 µg in cohort 1 and 2, respectively.³

Main outcomes for the study were similar to the phase 3 trial, and the results indicated that after 3 months, approximately 88% of patients achieved independence from conventional therapy while mean ADsCa was maintained within the target range of 7.8 to 9.0 mg per dL. Further, eneboparatide was observed to induce a rapid and sustained reduction of mean 24-hour urinary calcium, including in patients with hypercalciuria. Additionally, bone turnover markers increased slightly, and density remained unchanged. Eneboparatide was also observed to be well-tolerated without any serious adverse events.³

“The current standard of care treatment, oral calcium and vitamin D supplementation, seldom controls the life-altering symptoms and complications of hypoparathyroidism, with many patients at risk of declining kidney function and diminished bone quality,” said Mark Sumeray, MD, chief medical officer, in the press release. “In studies to date, eneboparatide has been shown to normalize mean serum calcium and mean urinary calcium excretion while restoring balanced bone turnover. Building upon findings from our successful phase 2 clinical trial, we are working diligently to execute our ongoing CALYPSO phase 3 study and look forward to topline data in 2025.”¹

References

1. GlobalNewswire. Amolyt Pharma Granted FDA Fast Track Designation for Eneboparatide for the Treatment of Hypoparathyroidism. News release. May 2, 2024. Accessed May 2, 2024. https://www.globenewswire.com/news-release/2024/05/02/2874145/0/en/Amolyt-Pharma-Granted-FDA-Fast-Track-Designation-for-Eneboparatide-for-the-Treatment-of-Hypoparathyroidism.html

2. Evaluation of the Safety and Efficacy of Eneboparatide (AZP-3601) in Patients With Chronic Hypoparathyroidism (CALYPSO). ClinicalTrials.gov identifier: NCT05778071. Updated March 25, 2024. Accessed May 2, 2024. https://www.clinicaltrials.gov/study/NCT05778071

3. Takacs I, Mezosi E, Soto A, et al. An Open-Label Phase 2 Study of Eneboparatide, a Novel PTH Receptor 1 Agonist, in Hypoparathyroidism. J Clin Endocrinol Metab. Published online March 6, 2024. doi:10.1210/clinem/dgae121