Entera Bio Reports Positive Results from a Phase 2 PK/PD Study of Oral PTH (1-34) in Patients with Hypoparathyroidism
- Results of a Phase 2 PK/PD study of Oral PTH (1-34) in patients with hypoparathyroidism were presented at the
American Society for Bone and Mineral Research Annual Meeting - Data suggest favorable pharmacologic and pharmacokinetic profiles of Entera’s Oral PTH formulation with a flexible oral dosing regimen vs. an injectable form of PTH
- Data will inform the Phase 2b/Phase 3 clinical development strategy
“Entera’s previous Phase 2 study in hypoparathyroid patients presented in 2016 showed that four times daily (QID) dosing of oral hPTH (1-34) had a positive effect on serum calcium, a reduction in serum phosphate and a reduction in urinary calcium. The goal of this new PK/PD study was to compare twice-daily (BID), three times daily (TID) and QID dosing regimens and dose strengths of Entera’s Oral hPTH (1-34) over a 24-hour period. The results showed that the largest changes in PD endpoints were found with QID dosing, with moderate changes in PD endpoints generally found with BID and TID dosing. In addition, the QID dosing decreased urine calcium over 24-hours, which indicates that it may be able to reduce urinary calcium in hypoparathyroid patients with hypercalciuria during long-term treatment,” stated Professor
“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. We as clinicians find the severity of disease is a continuum that is best treated by custom titration calcium and each drug to each patient’s needs,” stated Dr.
PK/PD Study Design
The Phase 2 PK/PD Study was open-label, and employed a 2-period partial crossover design to evaluate the PK and PD profiles of two doses, 0.75 mg and 2.25 mg, and three regimens (BID, TID and QID) of Oral hPTH (1-34) and included subcutaneous Natpar® [hPTH (1-84)] 100 µg once daily. The study was conducted in sixteen patients with hypoparathyroidism at the
Preliminary results from Part 1 of this study, were reported by
The full data set is being prepared for publication in a leading medical journal, and the poster presentation is available on the “Events” section of
The conclusions of the poster presentation indicate that:
- Oral hPTH(1-34) 2.25 mg QID for one day is associated with an increase in serum albumin-corrected calcium and 1,25(OH)2D (1,25-dihydroxyvitamin D), a decrease in serum phosphate, and a decrease in urinary calcium in patients with hypoparathyroidism. The patients also received calcium supplements and either alfacalcidol or calcitriol.
- Oral PTH produced similar biological effects to Natpara® 100 µg QD, the highest dose of hPTH (1-84) currently indicated for use in patients with hypoparathyroidism, on serum calcium, phosphate and Vit D. Additionally, Oral hPTH (1-34) effected a decrease in urinary calcium. These changes in serum PD parameters were sustained over the 24-hour period of observation from time zero.
- BID, TID and QID regimens showed a dose-dependent increase in 1,25(OH)2D indicating that the long-term treatment, even with the less frequent regimens, may be an effective treatment option for those patients suffering from less severe hypoparathyroidism.
- Treatment with Oral hPTH (1-34) dosed at multiple times during the day has the potential to reduce calciuria generally associated with maintenance of serum calcium within the normal range using calcium supplements and calcitriol analogs alone.
- There were no treatment-emergent adverse events of hypercalcemia, as well as no treatment-emergent Serious Adverse Events reported in the study.
About Hypoparathyroidism
Hypoparathyroidism is a rare condition in which the body produces insufficient amounts of PTH. Individuals with a deficiency of PTH typically exhibit abnormally low levels of calcium in the blood, or hypocalcemia, and high levels of phosphate in the blood, or hyperphosphatemia. Hypoparathyroidism is estimated to affect approximately 77,000 individuals in the
*Natpara® is the brand name used in United States for Natpar® which is sold by Takeda in Europe. Natpar® was used in this Phase 2 clinical trial.
About
Entera has developed a proprietary platform technology that enables oral delivery of biologicals and large molecule drugs, which are typically delivered via injections and or other non-oral pathways. However, oral drug delivery is the easiest method for self-administering medications, offers patients greater dosing flexibility, and has the highest patient acceptance and compliance rates as compared to all other routes of drug administration. The Company employs this technology for its own pipeline products and may enter into licensing agreements with biopharma companies for application of the technology to their proprietary compounds, such as the
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Entera Bio Ltd. Adam Gridley, CEO Tel: +972-2-532-7151 adam@enterabio.com | INTERNATIONAL INVESTOR RELATIONS Bob Yedid LifeSci Advisors 646-597-6989 bob@lifesciadvisors.com |
Source: Entera Bio Ltd.