EU CHMP recommends approval of Natpar (rhPTH[1-84]) in chronic hypoparathyroidism- Shire

Shire has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending the granting of Conditional Marketing Authorisation for Natpar (rhPTH[1-84]), a recombinant human protein with the full length 84–amino-acid sequence of endogenous parathyroid hormone (PTH), as an adjunctive treatment for adult patients with chronic hypoparathyroidism who cannot be adequately controlled with standard therapy alone.

The CHMP submission was based on outcomes from the Phase III efficacy and safety of rhPTH(1-84) in hypoparathyroidism clinical trial (REPLACE) in patients aged 18-85 years with chronic hypoparathyroidism. In the double-blind, placebo-controlled, randomized Phase III study 134 patients with hypoparathyroidism were randomized in a ratio of 2:1 to either placebo or 50 micrograms once daily of rhPTH(1-84) for 24 weeks. The primary endpoint was a 50 percent or greater reduction from baseline in their daily dose of oral calcium and active vitamin D while maintaining a stable albumin corrected serum calcium concentration greater than or equal to baseline concentration (baseline was 2.12 mmol/L for the rhPTH(1-84) group and 2.15 mmol/L for the placebo group) and less or equal to the upper limit of normal (normal range 2.1–2.6 mmol/L) but ideally within the target range of 2.0–2.25 mmol/L. At the end of the follow-up period, 53 percent of the patients on rhPTH(1-84) achieved the primary endpoint compared with 2 percent of patients in the placebo group.

The overall incidences of adverse events were similar in both groups. By week 24, 93 percent of patients in the rhPTH(1–84) and 100 percent of patients in the placebo group had at least one adverse event, with hypocalcemia, muscle spasm, paraesthesias, headache, and nausea being the most common adverse events.