Doses of Oral hPTH(1-34) May Safely be Adjusted to Suit Needs of Patients with Hypoparathyroidism, Phase 2 Study Shows
The pharmacological properties of hPTH(1-34) allow the oral medication to be administered at different dosing regimens to suit the individual needs of patients with hypoparathyroidism, according to data from a Phase 2 study.
The findings were presented in the poster “An Evaluation of the Pharmacodynamic Effects of an Oral hPTH(1-34) formulation in Patients with Hypoparathyroidism,” during the recent American Society for Bone and Mineral Research (ASBMR) Annual Meeting, in Orlando, Florida.
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.
hPTH(1-34) is Entera Bio’s oral parathyroid hormone therapy containing a synthetic form of PTH which mimics the effects of the natural hormone in the body.
In a previous pilot Phase 2 study (NCT02152228), Entera had shown that oral hPTH(1-34) successfully restored mineral balance in a group of patients with hypoparathyroidism, when administered four times daily.
The company has now presented findings from a new Phase 2 study (NCT03516773) that compares the pharmacological properties of three different dosing schedules (two, three, and four times daily) and two different dose strengths (0.75 and 2.25 mg) of hPTH(1-34) in 16 patients with hypoparathyroidism over a period of 24 hours.
The study used Natpara as an active control for comparison. Natpura is an injectable form of synthetic PTH developed by Shire (now part of Takeda Pharmaceutical Company), which has been approved by the U.S. Food and Drug Administration and the European Medicines Agency for the treatment of hypocalcemia (low levels of calcium in the blood) associated with hypoparathyroidism. It was administered through an under-the-skin injection, at the highest approved dose of 100 µg once a day.
All study participants were dosed while remaining on their routine medications (calcium supplements together with alfacalcidol or calcitriol) to control calcium levels.
Study findings presented at the ASBMR meeting have shown that all dosing schedules led to a dose-dependent increase in the levels of active vitamin D, indicating that long-term treatment with oral hPTH(1-34), even with longer dosing intervals, may be effective for patients with milder forms of hypoparathyroidism.
When administered at a dose of 2.25 mg four times a day, oral hPTH(1-34) increased the levels of active vitamin D and calcium in the serum, and decreased the levels of phosphate and calcium in the urine of patients with hypoparathyroidism over a period of 24 hours.
Oral hPTH(1-34) at a dose of 2.25 mg four times a day restored mineral balance and levels of active vitamin D similarly to Natpara.
When administered several times a day, oral hPTH(1-34) may lower the risk of calciuria (high levels of calcium in the urine) associated with the use of calcium supplements and calcitriol to keep the levels of calcium in the blood within a normal range.
“These data again show the ability of Entera’s oral formulation to deliver PTH to the bloodstream at concentrations that produced the anticipated [pharmacodynamic] effect,” Sofia Ish-Shalom, professor and principal investigator at the Endocrine Research Center at Lin Medical Center in Haifa, Israel, said in a news release.
Importantly, no treatment-emergent adverse events of hypercalcemia (high levels of calcium in the blood), or other treatment-emergent serious adverse events were reported in the study.
“The data from this study suggest that our oral PTH delivered at different frequencies, and with different doses, can be used effectively to customize the therapy of individual patients. For example, some patients with elevated urinary calcium might be well served with more frequent dosing three or four times daily, while patients who have milder disease might be adequately served by less frequent twice-a-day dosing,” Arthur Santora, chief medical officer of Entera, said.
“[D]ata from this study will be very valuable in helping optimize the formulation of oral hPTH (1-34) for hypoparathyroidism, as well as designing long-term studies of a diverse hypoparathyroid population, ” he added.
Full data from the study is currently being prepared for publication in a renowned medical journal.