Recombinant PTH Improves Mineral Balance in Chronic Hypoparathyroidism, RACE Trial Shows

Long-term use of recombinant human parathyroid hormone, or rhPTH(1-84), improves mineral balance and normalizes the levels of calcium in the urine of people with chronic hypoparathyroidism, a Phase 3 trial shows.

The latest trial findings were discussed at the 28th Annual Scientific & Clinical Conference of the American Association of Clinical Endocrinologists (AACE), held recently in Los Angeles. The poster presentation was titled, “Safety and Efficacy of Recombinant Human Parathyroid Hormone 1-84 for the Treatment of Adults With Chronic Hypoparathyroidism: Six-Year Results of the RACE Study.”

Hypoparathyroidism is caused by low levels of parathyroid hormone (PTH) in the body, which often results in an imbalance of minerals, especially calcium. The condition is considered chronic when a patient’s blood levels of PTH and calcium remain low for more than six months.

rhPTH(1-84) is a synthetic form of PTH that can be injected in the body to mimic the effects of PTH. It was approved by the U.S. Food and Drug Administration in 2015 and by the European Medicines Agency in 2017 for the treatment of hypocalcemia (low levels of calcium in the blood) associated with hypoparathyroidism.

It is available in the U.S. as Natpara, and in the E.U. as Natpar, marketed by Shire (now part of Takeda).

Long-term therapeutic effects of rhPTH(1-84) on mineral balance in people with chronic hypoparathyroidism were assessed in a 6-year, open-label Phase 3 trial, RACE (NCT01297309).

The study enrolled a total 49 patients with chronic hypoparathyroidism from 12 U.S. centers. Participants received either 25 or 50 µg of rhPTH(1-84) per day. The therapy was administered by subcutaneous (under the skin) injection, with dose adjustments to a maximum of 100 µg per day, if needed. Oral doses of calcium and calcitriol (vitamin D) also were adjusted as needed to maintain the calcium levels within the target range of 8.0-9.0 mg/dL.

A total of 34 patients (69.4%) completed 72 months of treatment with rhPTH(1-84), after which they reduced oral doses of calcium by 40.4% and calcitriol by 72.2%. Further, 22 of the 34 patients (64.7%) who completed the entire course of treatment were able to maintain their calcium levels within a normal range, while reducing their intake of oral calcium and calcitriol by at least 50%.

The levels of calcium in the urine lowered from above-normal values at the start of the trial (356.7 mg/day) to normal values after 72 months of treatment with rhPTH(1-84) (128.82 mg/day). Phosphorus levels also decreased from above-normal values (4.8 mg/dL) to a normal range at 72 months (4.0 mg/dL).

During the treatment period, mean creatinine levels and glomerular filtration rates (clinical parameters that assess kidney function) remained stable.

The treatment was generally considered to be safe and well-tolerated. Adverse events associated with the treatment were reported in 51% of the patients, but none of them were considered serious. The most common adverse events included muscle spasms, hypocalcemia, and sinusitis.

“Continuous use of rhPTH(1-84) over six years resulted in a favorable safety profile, was effective, and improved key measurements of mineral homeostasis [balance], notably normalization of urinary calcium,” researchers wrote.