The European Commission ( EC ) has granted Conditional Marketing Authorisation for Natpar ( rhPTH [ 1-84 ] ), the first recombinant human protein with the full length 84-amino acid sequence of endogenous parathyroid hormone ( PTH ).
Natpar is the first and only approved hormone therapy indicated as adjunctive treatment for adult patients with chronic hypoparathyroidism who cannot be adequately controlled with standard therapy alone.
The Conditional Marketing Authorisation is based on the outcomes from the phase III efficacy and safety of rhPTH (1-84) clinical trial ( REPLACE ) in patients aged 19-74 years with chronic hypoparathyroidism.
The trial showed that Natpar maintained serum calcium while reducing oral calcium and active vitamin D supplemental doses.
Hypoparathyroidism is a rare disease that occurs when inadequate levels of PTH are secreted by the parathyroid glands, resulting in a mineral imbalance in the body expressed by a low concentration of calcium ( hypocalcemia ) and a high concentration of phosphate ( hyperphosphatemia ) in the blood.
Guidelines from the European Society of Endocrinology ( ESE ) state that a diagnosis of chronic hypoparathyroidism should be considered in a patient with hypocalcemia and an inappropriately low PTH concentration. Guidelines recommend that treatment should aim to restore mineral homeostasis and prevent symptoms of hypocalcemia while optimizing overall well-being.
Typical symptoms of hypocalcemia include muscle spasms and cramping.
To date, management of chronic hypoparathyroidism has focused on maintaining serum calcium with oral calcium and active vitamin D supplements; however, some patients are not adequately controlled and still have variations in their serum calcium levels.
Natpar is a recombinant human PTH and is available as a 25, 50, 75 and 100 micrograms once-daily injection as adjunctive treatment for adult patients with chronic hypoparathyroidism who cannot be adequately controlled with standard therapy alone.
Natpar is approved in the United States under the trade name Natpara ( parathyroid hormone ).
In the double-blind, placebo-controlled, randomized phase III study 124 patients with hypoparathyroidism were randomized in a ratio of 2:1 to either 50 micrograms once daily of rhPTH (1-84) or placebo for 24 weeks.
The primary endpoint was a 50% 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 2.1 mmol/L for the rhPTH [1-84] group and 2.2 mmol/L for the placebo group ) and less or equal to the upper limit of normal ( normal range 2.1-2.6 mmol/L ).
At the end of the treatment period, 54.8% of the patients on rhPTH (1-84) achieved the primary endpoint compared with 2.5% of patients in the placebo group ( p less than 0.0001 ).
There were no differences in the proportion of patients maintaining a stable albumin corrected serum calcium concentration at the end of treatment between subjects randomized to rhPTH (1-84) and placebo.
The most common side effects with Natpar ( which may affect more than 1 in 10 people ) are too high or too low blood calcium levels, which can lead to headache, diarrhoea, vomiting, paraesthesia ( unusual sensations like pins and needles ), hypoaesthesia ( reduced sense of touch ) and high calcium levels in the urine.
Natpar must not be used in patients who are having or have had radiation therapy to the bones, who have bone cancer or cancer that has spread to the bones and are at increased risk of developing a bone cancer called osteosarcoma.
Natpar must also not be used in patients who have unexplained increases in the levels of an enzyme called bone alkaline phosphatase and those who have pseudohypoparathyroidism, a rare disease where the body does not respond adequately to the parathyroid hormone produced by the body. ( Xagena )
Source: Shire, 2017