Positive results from the CALYPSO Phase III trial showed that eneboparatide (AZP-3601), an investigational parathyroid hormone (PTH) 1 receptor agonist, met its composite primary endpoint, demonstrating a statistically significant and clinically meaningful normalisation of albumin-adjusted serum calcium (sCa) levels and independence from active vitamin D and oral calcium supplements in adults with chronic hypoparathyroidism (HypoPT) at week 24. These late-breaking results were presented today at the European Congress of Endocrinology (ECE) in Prague, Czech Republic.1

In the trial, 31.1% of patients treated with eneboparatide met the composite primary endpoint, achieving sCa within normal range (8.3-10.6 mg/dL) and independence from oral supplements at week 24, compared with 5.9% of patients in the placebo group (eneboparatide: n=41/132; placebo: n=4/68; p=0.0001). Immunogenicity was observed in the majority of patients, resulting in reduced treatment effects in some patients. sCa was controlled with the aid of supplements and up-titration of eneboparatide.1

CALYPSO also met all key secondary endpoints at week 24, including normalisation of urinary calcium (uCa) excretion in patients with hypercalciuria at baseline. This was achieved in 56.6% of these patients in the eneboparatide group compared to 20% in the placebo group (eneboparatide: n=43/76; placebo: n=9/45; p=0.0001). Eneboparatide also demonstrated statistically significant improvements in patient-reported outcomes reflecting disease-specific core physical symptoms and physical functioning, as well as SF-36 Physical Function Subscore (SF-36-PFS).1

After week 24, patients continued eneboparatide (ENB/ENB group) or were switched to eneboparatide from placebo (PBO/ENB group) for an additional 28-week open-label extension (OLE) period. In the ENB/ENB group, clinical benefits were maintained through week 52 with some use of oral supplements, as assessed by OLE efficacy endpoints.1

Maria Luisa Brandi, MD, PhD, IRCCS European Institute of Oncology, Milan, Italy, and investigator in the trial, said: "As the underlying cause of HypoPT, inadequate PTH activity affects more than serum calcium levels, disrupting multiple body systems and significantly diminishing quality of life. The results from the CALYPSO Phase III trial demonstrate the potential for eneboparatide to stabilise serum calcium while preserving kidney and bone health, outcomes that are critical for improved patient functioning and successful long-term treatment."

Gianluca Pirozzi, Senior Vice President, Head of Development, Regulatory and Safety, Alexion, AstraZeneca Rare Disease, said: "The breadth of data from CALYPSO, the largest global trial conducted in adults with HypoPT, demonstrates eneboparatide's potential to deliver meaningful and sustained benefits in calcium regulation, symptom burden, physical function and bone health through functional restoration of PTH action. These effects were maintained through 52 weeks, supporting eneboparatide's potential to address the broad burden of this complex rare disease and help close persistent gaps in care, given the limited treatment options available."

Bone health was preserved over 52 weeks, evidenced by increases in biomarkers procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide (CTX) that remained within a normal range, consistent with balanced bone turnover, and no clinically significant reduction in bone mineral density (BMD), as measured by BMD T- and Z-scores.1

Eneboparatide was well tolerated over 52 weeks of treatment. The majority of treatment-emergent adverse events (TEAEs) were balanced between the eneboparatide group and the placebo group through week 24, and the overall safety profile remained consistent through week 52.1