お知らせ • Mar 05
Entera Bio Submits Streamlined Phase 3 Protocol to Initiate Registrational Program for EB613 in Postmenopausal Women with Osteoporosis
Entera Bio Ltd. submitted to the U.S. Food and Drug Administration (FDA) a clinical amendment providing a streamlined Phase 3 protocol, statistical analysis plan (SAP), and open-label extension synopsis to the Company’s Investigational New Drug (IND) 505(b)(2) submission, to evaluate EB613 (Oral PTH(1-34), teriparatide). Entera anticipates FDA feedback within 60 days. EB613 is the first oral anabolic (bone forming) tablet treatment in Phase 3 development for the treatment of osteoporosis. The FDA submission relies on the combination of Entera’s oral peptide platform, N-Tab®, the Listed Drug (LD) Forteo® (teriparatide SC injection, Eli Lilly), which has been in clinical use for over 20 years with a well-established benefit-risk profile, prior FDA alignment and recent landmark regulatory recognition of total hip BMD as an acceptable primary endpoint for fracture. Entera is seeking the same indications as Forteo®. The planned Phase 3 trial will consist of a multinational, randomized, double-blind, placebo-controlled safety and efficacy study in 750 women with postmenopausal osteoporosis to evaluate the percentage change in total hip BMD from baseline to month 12 (rather than month 24) as the primary outcome measure. The required target enrolment for this study is significantly lower than previous development assumptions, substantially streamlining trial execution while accelerating the potential path to approval. The study is powered to demonstrate increases in total hip BMD, which are comparable with reported outcomes for Forteo® at 12 months, which is associated with a 60% to 80% relative reduction in vertebral fracture risk. EB613 achieved comparable increases in total hip BMD in its placebo-controlled 6-month Phase 2 study, as those reported for Forteo® at 6-months. The 12-month phase 3 study and the scientific bridge to Forteo® are planned to be submitted in support of the NDA. Entera plans to advance the final single tablet formulation of EB613 (Next-Gen EB613) directly into the Phase 3, replacing the previous multi-tablet candidate. This strategic advancement positions the Company to pursue approval and commercialization of a simplified once-daily oral anabolic therapy without the need for future bridging development between formulations. The Company expects to initiate the Phase 3 study in late 2026, with topline results anticipated in the second half of 2028 - approximately one year earlier than previously expected. Entera also submitted to the FDA a protocol synopsis for a 12-month open-label extension study in which participants would be randomized to EB613 through 12 or 24 months of treatment or transition to a standard of care anti-resorptive agent. The extension study is expected to run in parallel with the NDA review. Substantial evidence supports the efficacy of anabolic therapies over bisphosphonates for lowering fracture risk in osteoporosis patients at high risk. However, all available anabolic therapies are administered by subcutaneous (SC) injection and used in a minority of eligible patients. Entera’s EB613 program (oral PTH (1-34), teriparatide), is being developed as the first oral, once-daily anabolic tablet treatment for osteoporosis. EB613 completed a phase 2, 6-month, 161-patient, placebo-controlled study that met all biomarker and BMD endpoints without significant safety concerns in women with postmenopausal osteoporosis or low BMD (JBMR 2024). EB613 produced rapid dose-proportional increases in biochemical markers of bone formation, reductions in markers of bone resorption, and increased lumbar spine, total hip, and femoral neck BMD. The effects of EB613 on trabecular and cortical bone using 3D-DXA showed increases with EB613 compared with placebo in a variety of indices, including integral volumetric BMD and trabecular volumetric BMD, cortical thickness, and cortical surface BMD. Mechanistically, the findings suggest that bone strengthening, and fracture resistance may occur rapidly with EB613. Furthermore, the data are consistent with those of published subcutaneous teriparatide at the 6-month time point.