Entera Bio reports up to 4.23% total hip and 4.22% lumbar spine BMD gains with oral EB613 in a small post-hoc Phase 2 osteoporosis subgroup.
Written By: Mayuri Vaja, PharmD
Reviewed By: Pharmacally Editorial Team
Entera Bio reported new Phase 2 findings suggesting greater bone mineral density (BMD) gains with EB613, an investigational oral parathyroid hormone (PTH[1-34]) tablet, among postmenopausal women with osteoporosis than among participants with higher baseline BMD. Presented at the American Society for Bone and Mineral Research (ASBMR) 2026 Annual Meeting, the post-hoc analysis provides exploratory evidence supporting further evaluation of EB613 in women at high risk of fracture.
The company also presented the design of its planned registrational Phase 3 trial, which will evaluate EB613 against placebo over 12 months. The findings remain preliminary and do not establish whether treatment reduces fracture incidence.
Post-Hoc Analysis Shows Greater BMD Gains in the Osteoporosis Subgroup
The six-month Phase 2 study enrolled 161 postmenopausal women with low bone mass or osteoporosis who received placebo or one of four EB613 dose levels. The post-hoc analysis focused on participants receiving EB613 2.5 mg daily and examined outcomes according to baseline BMD T-scores.
At six months, participants with baseline T-scores of −2.5 or lower showed placebo-adjusted BMD increases of 4.23% at the total hip (n=6) and 4.22% at the lumbar spine (n=9). Among participants with T-scores above −2.5, the corresponding increases were 1.02% at the total hip (n=15) and 1.59% at the lumbar spine (n=12).
Across all 21 participants included in the 2.5 mg analysis, placebo-adjusted BMD increased by 1.84% at the total hip and 2.72% at the lumbar spine.
Changes in P1NP, a marker of bone formation, and CTX, a marker of bone resorption, were also reported to be somewhat larger and more persistent among women with T-scores of −2.5 or lower.
These findings suggest that baseline skeletal status may be relevant to evaluating EB613’s effects. However, the analysis was conducted after the original study, and the subgroup sizes were small. The findings therefore cannot establish that EB613 produces a definitively greater treatment effect in osteoporosis than in less severe bone loss. The differing sample sizes across skeletal sites also warrant caution when comparing the results.
Planned Phase 3 Trial Will Assess BMD at 12 Months
Entera presented a multinational, randomized, double-blind, placebo-controlled Phase 3 study designed to enroll approximately 900 postmenopausal women aged 50–90 years with osteoporosis. Eligibility criteria include a BMD T-score of −2.5 or lower at the lumbar spine, total hip or femoral neck, and at least five years since the last menstrual period.
Participants will be randomized in a 2:1 ratio to receive EB613 (approximately 600 participants) or placebo (approximately 300 participants) for 12 months.
The primary endpoint is the change in total hip BMD at Month 12 compared with placebo. Secondary endpoints include changes in lumbar spine and femoral neck BMD at Month 12, as well as BMD changes at the total hip, lumbar spine and femoral neck at Months 3 and 6.
Safety assessments will include adverse events, vital signs, physical examinations and clinical laboratory tests. Pharmacokinetic assessments are planned in a subset of participants. Those completing the initial treatment period may enter an extension study to evaluate safety and durability of response through Months 18 and 24.
The latest presentation describes an enrollment target of approximately 900 participants, compared with approximately 750 in the Phase 3 plan described in Entera’s June 2026 regulatory update. The available announcements do not establish the reason for this change.
Oral PTH Therapy Remains an Investigational Approach
EB613 contains oral PTH(1-34), also known as teriparatide, and is being developed as a once-daily anabolic treatment. PTH-based anabolic therapies aim to stimulate bone formation and increase BMD. An oral formulation could offer an alternative to injectable anabolic treatments, although improved adherence, accessibility or clinical outcomes have not been demonstrated by the reported subgroup analysis.
Entera previously reported that its six-month Phase 2 study met its BMD and biomarker endpoints without significant safety concerns. These findings provide preliminary support for continued development, but the planned Phase 3 trial will be important for evaluating efficacy and safety in a larger population.
The key question is whether the BMD improvements observed in Phase 2 can be confirmed in the registrational study. Even if the Phase 3 trial demonstrates a BMD benefit, the reported findings alone do not establish fracture-risk reduction. EB613 remains investigational, and its safety and efficacy for osteoporosis have not yet been established through Phase 3 evaluation.
Reference
Entera Bio, Entera Presents Markedly Enhanced Anabolic Effects of EB613 (First-in-Class Oral PTH(1-34) Tablet) in Postmenopausal Women with Osteoporosis at High Risk of Fracture and Showcases Phase 3 Design at ASBMR 2026 Annual Meeting, 13 October 2026
A Six-month Phase 2 Study of Oral hPTH(1-34) (EBP05) in Postmenopausal Women with Low Bone Mass, ClinicalTrials.gov ID NCT04003467
About the Writer
Mayuri Vaja (Linkedin) is a Pharm.D professional with a strong interest in clinical research, pharmacovigilance, and medical writing, supported by certifications in pharmacovigilance and academic projects exploring AI in healthcare and drug safety.
With a growing focus on evidence-based healthcare and scientific communication, she is developing expertise in clinical research and translating healthcare evidence into clear, meaningful content.
As a Pharmacally healthcare writer, Mayuri is committed to creating accurate, research-driven, and clinically relevant healthcare content while continuously strengthening her professional skills.