Real-world data for effectiveness and safety of palopegteriparatide in patients with chronic hypoparathyroidism: the PaTH REAL study.

CONTEXT: Chronic hypoparathyroidism (HypoPT) is a rare endocrine disorder characterized by hypocalcemia and hyperphosphatemia, requiring lifelong treatment with activated vitamin-D and oral calcium supplements. Palopegteriparatide, a novel long-acting prodrug of PTH (1-34), has demonstrated efficacy in randomized controlled trials, but real-world data on its long-term effectiveness and safety remain limited.

OBJECTIVE

To evaluate the efficacy and safety of long-term palopegteriparatide therapy in a real-world cohort of patients with HypoPT.

DESIGN AND

SETTING

Multicenter prospective cohort study conducted in tertiary referral hospitals. The study is registered at ClinicalTrials.gov under the identifier NCT07299838.

PATIENTS AND INTERVENTION: Ninety-two adults with HypoPT (79 females, 13 males), previously treated with recombinant human PTH (1-84) or conventional therapy, initiated palopegteriparatide according to the National Hellenic Guidelines for the management of HypoPT.

RESULTS

Patients were treated for a median duration of 6.5 months (range 2-14), with significant improvements in biochemical control of calcium-phosphate metabolism. Albumin-adjusted calcium increased from 8.14 ± 0.73 to 8.99 ± 0.94 mg/dL, and magnesium from 1.79 ± 0.17 to 1.96 ± 0.17 mg/dL (both P < .001). Phosphate decreased from 4.74 ± 0.97 to 4.02 ± 0.63 mg/dL (P < .001), Ca × P product from 38.27 ± 6.92 to 36.04 ± 6.55 mg2/dL2 (P = .017), and 24-hour urinary calcium from 245.7 ± 125.5 to 164.5 ± 88.3 mg/24 h (P < .001). Daily pill burden was markedly reduced, and 58% of patients achieved independence from calcium supplements and alfacalcidol after a median of 30 days. Adverse events were mostly mild and transient.

CONCLUSIONS

In a real-world setting, palopegteriparatide effectively normalizes calcium-phosphate homeostasis, reduces hypercalciuria, and substantially decreases reliance on conventional therapy, with a favorable safety profile.