FDA Clears Phase 3 Path for Entera’s Oral Osteoporosis Therapy EB613

Entera Bio has received positive feedback from the U.S. Food and Drug Administration (FDA) on the registrational Phase 3 development program for EB613, an investigational oral formulation of teriparatide (PTH 1-34) for postmenopausal osteoporosis. The FDA agreed with the company’s proposed pivotal study design, providing a clear regulatory pathway toward a potential New Drug Application (NDA).

The agency accepted Entera’s plan to conduct a single randomized, double-blind, placebo-controlled Phase 3 trial in approximately 750 postmenopausal women with osteoporosis. The study will evaluate the percent change from baseline in total hip bone mineral density (BMD) at Month 12 as the primary endpoint.

According to the company, positive results from the study could support NDA submission under the FDA’s 505(b)(2) pathway, utilizing a scientific bridge to Forteo® (teriparatide injection) along with additional clinical evidence.

EB613 and the Need for Oral Anabolic Therapy

Osteoporosis is a chronic skeletal disorder characterized by reduced bone strength and increased fracture risk. More than two million osteoporotic fractures occur annually in the United States, with postmenopausal women representing one of the highest-risk populations.

While anabolic therapies stimulate new bone formation and reduce fracture risk more effectively than many antiresorptive treatments in high-risk patients, currently approved anabolic agents require subcutaneous administration. As a result, anabolic therapies remain underutilized despite strong clinical evidence supporting their use.

EB613 is being developed as a once-daily oral tablet containing teriparatide, potentially becoming the first oral anabolic therapy for osteoporosis. The oral formulation may improve treatment accessibility and patient adherence compared with injectable therapies.

Phase 3 Design and Regulatory Strategy

The planned Phase 3 trial will enroll approximately 750 postmenopausal women with osteoporosis and compare EB613 with placebo over 12 months.

The FDA agreed that total hip BMD at Month 12 can serve as the primary efficacy endpoint for the registrational study. Entera stated that the trial is powered to demonstrate increases in total hip BMD comparable to outcomes reported with Forteo at 12 months. Published evidence suggests such improvements are associated with a 60% to 80% relative reduction in vertebral fracture risk.

The proposed NDA package will include a scientific bridge analysis to Forteo under the 505(b)(2) regulatory pathway and findings from a transiliac crest bone biopsy substudy conducted in a subset of participants.

The FDA also agreed with Entera’s proposal to continue monitoring patients in a separate open-label extension study through 24 months. Data through 18 months will be included as part of the NDA safety update, while complete two-year results will provide additional information on long-term safety, durability of treatment effect, and treatment sequencing with antiresorptive therapy.

Phase 2 Efficacy and Safety Data

The Phase 3 program is supported by findings from a placebo-controlled Phase 2 study (NCT04003467) involving 161 postmenopausal women with osteoporosis or low BMD.

The study met both primary and secondary endpoints, demonstrating statistically significant increases in lumbar spine, total hip, and femoral neck BMD. EB613 also produced rapid increases in biomarkers of bone formation while reducing markers of bone resorption.

No significant safety concerns were reported during the study.

Additional data presented during ENDO 2026 showed that a single-tablet formulation of EB613 achieved pharmacokinetic and pharmacodynamic profiles comparable to both the multi-tablet formulation evaluated in Phase 2 and injectable Forteo. These findings support the company’s efforts to advance a simplified once-daily oral dosing regimen into late-stage development.

Development Timeline

Entera plans to initiate the Phase 3 registrational study in late 2026, with topline data expected during the second half of 2028.

Chief Executive Officer Miranda Toledano stated that the FDA feedback provides a clear registrational pathway for EB613 and supports the company’s objective of expanding access to anabolic osteoporosis treatment through an oral formulation.

If the Phase 3 study confirms the efficacy and safety observed in earlier clinical trials, EB613 could become the first oral anabolic therapy approved for osteoporosis, offering a new treatment option for patients at elevated risk of fracture.

Reference

Entera Bio Receives Positive FDA Feedback on 12-Month Registrational Phase 3 Study for EB613 – the First Oral Anabolic Tablet in Development for Postmenopausal Women with Osteoporosis – EnteraBio