Hypoparathyroidism is a rare disorder characterized by a deficiency in parathyroid
hormone (PTH) resulting in hypocalcemia, hyperphosphatemia, and hypercalciuria. Eneboparatide
is an investigational peptide agonist of the PTH1 receptor for the treatment of chronic
hypoparathyroidism (HP).To evaluate the efficacy, safety, and tolerability of eneboparatide
in HP patients.Open-label, phase 2 study.Twenty-eight patients (21 women, 7 men),
mean age (range): 58 years (28-72), with HP were enrolled into 2 consecutive cohorts
(C1, n = 12, and C2, n = 16).Following an optimization period, daily subcutaneous
injections of eneboparatide were administered for 3 months at 20 µg/day (C1) or 10
µg/day (C2) starting dose. Conventional therapy was progressively removed and eneboparatide
could be titrated up to 60 µg (C1) or 80 µg (C2).Proportion of patients achieving
independence from conventional therapy, albumin-adjusted serum calcium (ADsCa), 24-h
urine calcium (uCa), serum bone turnover markers (s-CTX and P1NP), bone mineral density
(BMD), and adverse events (AEs).After 3 months, ≥ 88% patients achieved independence
from conventional therapy while mean ADsCa was maintained within target range (7.8-9
mg/dL). Eneboparatide induced a rapid and sustained reduction of mean 24-hour uCa,
even among patients with hypercalciuria. Bone turnover markers slightly increased
and BMD remained unchanged, consistent with progressive resumption of physiologic
bone turnover. Eneboparatide was well tolerated with no serious AEs.Eneboparatide
allowed independence from conventional therapy and maintenance of serum calcium within
a target range, while normalizing uCa excretion and producing a balanced resumption
of bone turnover.
