FDA fast tracks PTH1 receptor agonist for treatment of hypoparathyroidism
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Key takeaways:
- Eneboparatide is an investigational drug for hypoparathyroidism designed to produce sustained and stable calcium levels.
- The agent is currently being investigated in the phase 3 Calypso trial.
The FDA granted fast track designation for an investigational parathyroid hormone 1 receptor agonist to treat hypoparathyroidism, according to an industry press release.
Eneboparatide (Amolyt Pharma) is a therapeutic peptide designed to bind to the PTH receptor to produce sustained and stable levels of calcium in the blood, allowing the drug to control symptoms of hypoparathyroidism, and limit urine calcium excretion by restoring calcium reabsorption by the kidney.
Eneboparatide is currently being investigated in the phase 3 Calypso trial. According to the release, the randomized, double-blind, placebo-controlled trial will randomly assign about 165 participants with chronic hypoparathyroidism, 2:1, to receive eneboparatide or placebo. The primary efficacy endpoint will be the percentage of participants achieving an albumin-adjusted serum calcium within the normal range and independence from standard hypoparathyroidism care at 24 weeks. Secondary endpoints include normalization of 24-hour urine calcium for people with hypercalciuria at baseline and assessment of physical and cognitive function and quality of life. Bone quantity and quality will be analyzed as an additional exploratory endpoint. After the 24-week placebo-controlled period, all participants will receive eneboparatide during a 28-week open-label extension phase of the trial.
“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,” Mark Sumeray, MD, chief medical officer for Amolyt Pharma, said in the 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.”
Perspective
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The conventional treatment for hypoparathyroidism, calcium and active vitamin D, does not replicate the physiologic action of PTH. The resulting hypercalciuria and hyperphosphatemia lead to significant long-term complications for many patients. Therefore, clinicians have to find a balance between symptomatic hypocalcemia and long-term complications.
The half-life of native PTH is short. This characteristic would necessitate multiple daily injections to achieve a therapeutic effect lasting 24 hours. To address this, novel avenues are being pursued in different formulations to provide long-lasting therapeutic effects while simultaneously focusing on patient convenience, adherence and health outcomes in hypoparathyroidism.
Thomas Gardella, PhD, and his group in the Endocrine Unit at the Massachusetts General Hospital developed the long-acting parathyroid molecule that is now named ebenoparatide. Eneboparatide, a PTH analog with a unique receptor profile, is expected to provide long-lasting effects. Thus far, studies support the ability of eneboparatide to improve key parameters — mean serum calcium and urinary calcium excretion. Eneboparatide also increases bone turnover that is suppressed in hypoparathyroidism.
The FDA’s decision to grant fast-track designation to eneboparatide underscores the potential of this treatment to offer a new, effective option for managing hypoparathyroidism by adequately and consistently controlling blood calcium levels, decreasing urinary calcium excretion and improving quality of life.
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