Entera Bio Reports Breakthrough in Oral PTH Therapy for Hypoparathyroidism with Once-Daily Tablet
核心洞察
Entera Bio's proprietary long-acting PTH analog achieved sustained calcium elevation for over three days from a single oral tablet in preclinical studies, supporting once-daily dosing potential.
The novel PTH analog demonstrated markedly longer plasma half-life compared to unmodified PTH(1-34) (搜索) controls, which showed no calcium response in the minipig study.
This development represents a significant advancement from Entera's previous Phase 2 study that required four-times-daily dosing, potentially transforming treatment for hypoparathyroidism (搜索) patients.
Entera Bio Ltd. announced positive preclinical data for its EB612 program, demonstrating that a proprietary long-acting parathyroid hormone (PTH) analog achieved sustained calcium elevation for over three days from a single oral tablet. The findings support development of the first once-daily oral PTH replacement therapy for patients with hypoparathyroidism (搜索), potentially eliminating the need for daily injections currently required with existing treatments.
Novel PTH Analog Shows Extended Duration of Action
The preclinical study conducted in minipigs demonstrated that Entera's lead PTH variant achieved a markedly longer plasma half-life compared to unmodified PTH(1-34) (搜索) controls at the same dose. Serum calcium levels increased for more than three days in all five animals receiving the proprietary analog, with the sustained elevation correlating with prolonged pharmacokinetic exposure. In contrast, unmodified PTH(1-34) control tablets did not increase serum calcium levels.
"Our focus for the EB612 program has been finding the right long-acting, proprietary PTH analog to develop a single, once-a-day PTH tablet treatment for patients with hypoparathyroidism (搜索)," said Miranda Toledano, Chief Executive Officer at Entera. "Given the heterogeneity of this condition which requires PTH as a replacement therapy, our goal is to provide a single, daily tablet at fixed doses to help patients and their caregivers personalize titration and long-term care."
Addressing Current Treatment Limitations
Hypoparathyroidism (搜索) is a rare endocrine disorder characterized by deficient PTH production, hypocalcemia (搜索), and hyperphosphatemia (搜索). The current standard of care historically included high-dose calcium and calcitriol supplementation, but raising serum calcium to normal physiological levels in the absence of PTH frequently leads to elevated urinary calcium and is often associated with ectopic calcification, including nephrocalcinosis (搜索) and renal failure (搜索).
The only approved PTH replacement treatment, YORVIPATH®, requires patients to administer daily injections, while investigational candidates may require weekly injections. Entera's oral approach could significantly improve patient compliance and quality of life by eliminating injection requirements.
Building on Previous Clinical Success
Entera previously demonstrated proof of concept for its EB612 program in a Phase 2, 16-week study that enrolled 19 patients with hypoparathyroidism (搜索). The Phase 2 study, published in JBMR in 2021, demonstrated a 42% reduction (p=0.001) from baseline in median calcium supplement use while maintaining serum calcium levels above the lower limit for hypoparathyroidism patients (>7.5 mg/dL) throughout the study. However, that trial involved a four-times-daily dosing regimen.
The current preclinical data represent a key advancement toward addressing this dosing burden with a single, once-daily tablet using Entera's proprietary N-Tab® oral peptide platform technology.
Study Design and Safety Profile
The confirmatory minipig study involved administering a single oral tablet to five animals, with pharmacokinetic and pharmacodynamic profiles monitored over five days using an unmodified PTH(1-34) (搜索) tablet as control. No adverse events were observed during the study period.
Entera conducted in vitro and in vivo validation of various proprietary long-acting PTH analogs with a new generation of its N-Tab® oral peptide platform before identifying the lead candidate. The company plans to present these data at an upcoming medical conference.
Broader Pipeline Development
Beyond the EB612 program for hypoparathyroidism (搜索), Entera is developing EB613, an oral PTH(1-34) (搜索) treatment for postmenopausal women with osteoporosis (搜索) at risk of fracture. A placebo-controlled, dose-ranging Phase 2 study of EB613 tablets (n=161) met primary pharmacodynamic/bone turnover biomarker and secondary bone mineral density endpoints.
The company is also developing oral formulations of oxyntomodulin (搜索) for obesity (搜索) and metabolic syndromes, and oral GLP-2 (搜索) peptide for rare malabsorption conditions such as short bowel syndrome (搜索) in collaboration with OPKO Health (搜索).