Parathyroid hormone 1-84(Chongqing Kerun Biologic Pharmaceutical Development Co Ltd)

Hypoparathyroidism (HypoPT) is a rare disease, often inadequately controlled by conventional treatment. PARALLAX was a mandatory post-marketing trial assessing pharmacokinetics and pharmacodynamics of different dosing regimens of recombinant human parathyroid hormone 1–84 (rhPTH[1–84]) for treating HypoPT. The present study (NCT03364738) was a phase 4, 1-yr open-label extension of PARALLAX. Patients received only 2 doses of rhPTH(1–84) in PARALLAX and were considered treatment-naive at the start of the current study. rhPTH(1–84) was initiated at 50 μg once daily, with doses adjusted based on albumin-corrected serum calcium levels. Albumin-corrected serum calcium (primary outcome measure), health-related quality of life (HRQoL), adverse events, and healthcare resource utilization (HCRU) were assessed. The mean age of the 22 patients included was 50.0 yr; 81.8% were women, and 90.9% were White. By the end of treatment (EOT), 95.5% of patients had albumin-corrected serum calcium values in the protocol-defined range of 1.88 mmol/L to the upper limit of normal. Serum phosphorus was within the healthy range, and albumin-corrected serum calcium-phosphorus product was below the upper healthy limit throughout, while mean 24-h urine calcium excretion decreased from baseline to EOT. Mean supplemental doses of calcium and active vitamin D were reduced from baseline to EOT (2402–855 mg/d and 0.8–0.2 μg/d, respectively). Mean serum bone turnover markers, bone-specific alkaline phosphatase, osteocalcin, procollagen type I N-terminal propeptide, and type I collagen C-telopeptide increased 2–5 fold from baseline to EOT. The HCRU, disease-related symptoms and impact on HRQoL improved numerically between baseline and EOT. Nine patients (40.9%) experienced treatment-related adverse events; no deaths were reported. Treatment with rhPTH(1–84) once daily for 1 yr improved HRQoL, maintained eucalcemia in 95% of patients, normalized serum phosphorus, and decreased urine calcium excretion. The effects observed on urine calcium and the safety profile are consistent with previous findings.

NCT03364738.

This study assessed the risk of developing chronic kidney disease (CKD) and decline in estimated glomerular filtration rate (eGFR) over a period of up to 5 years in adult patients with chronic hypoparathyroidism treated with recombinant human parathyroid hormone (1‐84) (rhPTH[1‐84]) compared with a historical control cohort of patients not treated with rhPTH(1‐84).

Retrospective cohort study of patients with chronic hypoparathyroidism treated with rhPTH(1‐84) derived from the REPLACE (NCT00732615), RELAY (NCT01268098), RACE (NCT01297309) and HEXT (NCT01199614, and its continuation study NCT02910466) clinical trials and a historical control cohort who did not receive PTH selected from an electronic medical record database.

One hundred and eighteen patients treated with rhPTH(1‐84) and 497 patient controls.

Incident CKD was defined as ≥2 eGFR measurements <60 ml/min/1.73 m2 ≥3 months apart during the study and a sustained eGFR decline of ≥30% from baseline.

Over the 5‐year period, Kaplan–Meier analyses showed that rhPTH(1‐84)‐treated patients had a significantly lower risk of developing CKD (log‐rank p = .002) and a lower risk for a sustained eGFR decline ≥30% from baseline (log‐rank p < .001) compared with patients in the control cohort. In adjusted analyses, patients in the rhPTH(1‐84)‐treated cohort had a 53% lower risk of developing CKD (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.25–0.87) and a 65% lower risk for sustained eGFR decline ≥30% from baseline (HR, 0.35; 95% CI, 0.13–0.89) compared with controls.

Patients with chronic hypoparathyroidism treated with rhPTH(1‐84) in long‐term clinical trials had a significantly lower risk of developing CKD compared with patients in a historical control cohort not treated with rhPTH(1‐84).