Hypoparathyroidism is a disorder of mineral homeostasis characterize by deficient or absent parathyroid hormone. The associate clinical findings are hypocalcemia, hyperphosphatemia, and reduce tubular reabsorption of calcium, often leading to hypercalciuria.
Conventional treatment with oral calcium and activate vitamin D (calcitriol) doesn’t always maintain normal serum calcium levels and also doesn’t restore other physiologic actions of the missing parathyroid hormone, Bilezikian explain. The once-daily subcutaneous injectable drug was approve by the US Food and Drug Administration in 2015 and European Medicines Agency (Natpar) in 2017.
Long term safety
The new follow-up data are important, because the original phase 3 trial last only 26 weeks. These are patients who have a lifelong disease. With an approve drug you’d like to have long term safety and efficacy data. It continues to demonstrate efficacy and no safety concerns surface since the original study.
One new finding did arise in the 6 year data that was not see in the original phase 3 replace trial. Urine calcium levels eventually went down among the patients who receive rhPTH(1-84); whereas those levels hadn’t previously change significantly over 26 weeks. One of the main shortfalls of conventional therapy is that you get hypercalciuria and that can be damaging to the kidneys.
So if this indeed holds up that the urine calcium concentration will eventually fall; so that will mean this is a good way to go in those individuals in whom you can’t control the urine calcium by conventional therapy and other adjunctive therapy that we use to try and bring the urine calcium down. The RACE study, an open label extension of REPLACE and another phase 3 trial, enroll 49 patients from 12 US centers; of whom 82% were women with a mean age 48 years and hypoparathyroidism duration of about 16 years.
The primary endpoint
After the first year, 76% of patients had achieve the primary composite endpoint. By 72 months, 65% of the 34 patients who reach that time point met the primary endpoint. Among the 34 patients, there was a 40% reduction in oral calcium supplementation doses and a 72% reduction in calcitriol dose; so while albumin correct serum calcium levels were maintain within the target range (mean 8.4 mg/dL at baseline and 6 years).
Average serum phosphorus levels also decline rapidly and significantly from 4.8 mg/dL; so at baseline and was maintain at about 4.0 mg/dL through the 6 years. Calcium phosphate product also drop quickly; hence by an average of 9.5 mg2/dL2 lower than baseline at 6 years. Adverse events were report by most patients; alsothe most common drug relate adverse events were nausea, hypercalcemia, and hypocalcemia.
A quarter of the patients experience serious adverse events; but none were believe to be because of the drug. “No new safety concerns were identified,” said Bilezikian. Continuous use of rhPTH(1-84) over 6 years result in a favorable safety profile; hence was effective, and improve key measurements of mineral homeostasis; notably normalization of urinary calcium, the authors conclude.