Entera Bio Announces FDA’s Acceptance of Type D Meeting Review to Affirm Design of the Pivotal, Phase 3 Protocol for EB613 PTH Mini Tablets

Entera Bio Ltd . (NASDAQ:ENTX), (“Entera” or the “Company”) a leader in the development of orally delivered peptides and therapeutic proteins, today announced that a Type D meeting protocol review has been accepted by the U.S. Food and Drug Administration (FDA) to provide responses by March 30th, 2023. The pivotal, Phase 3 study protocol is entitled “A 24-Month Phase 3, Randomized, Double-Blind, Global Multicenter Study Comparing the Effects of Oral hPTH(1-34) (EBP05[EB613]) Daily Tablets vs. Placebo on Bone Mineral Density (BMD) in Postmenopausal Women with Osteoporosis.” EB613 is the first oral, once daily mini tablet presentation of hPTH (1-34), (teriparatide). EB613 has a well-established mechanism of action, PK and safety profile and met primary (PD/biomarker) and secondary endpoints (BMD) in a placebo controlled, dose ranging Phase 2 study in 161 postmenopausal women with low bone mass and osteoporosis.

As part of its briefing documents for the Type D process, Entera has submitted its Phase 3 protocol which reflects (1) the agreement reached during the Company’s September 2022 Type C Meeting discussion with FDA that a single 24 month Phase 3 placebo-controlled study could support a New Drug Application (NDA) submission under the 505(b)(2) regulatory pathway and (2) that Total Hip Bone Mineral Density (BMD) could serve as the primary endpoint for the registrational study. The objective of Type D meeting review is to confirm that the protocol fully meets FDA’s expectations, including the analysis of the primary endpoint and the population PK evaluations, ahead of potential study initiation in H2 2023.

The FDA previously agreed on major design elements of the protocol including the primary endpoint, enrollment criteria, titration and 2:1 randomization plan, and that 400 or more patients on EB613 is consistent with ICH E1A to support safety for the NDA. The current protocol reflects a 667/333 patient randomization, a 24 month total study duration and a futility interim analysis to occur when the last of the 300 first randomized subjects have completed 12 months in the study. Furthermore, Entera has provided power calculations for its primary endpoint, the change in TH BMD vs. placebo and for its key secondary endpoint which is designed to evaluate the change in TH BMD versus published surrogate threshold effects (STEs) that are associated with fracture risk reduction (Eastell 2022i).

“We look forward to continuing our incredibly collaborative dialogue with the FDA concerning what we anticipate as the last critical step prior to potentially initiating our Phase 3 pivotal study in H2 2023. Since receiving FDA’s End of Phase 2 minutes in January of 2022 which conveyed that the previously anticipated non-inferiority head-to-head design versus Forteo® Phase 3 design may not be favorable to the approvability of our program, the Company has undergone a massive leadership and operational shift to successfully pivot and align with FDA’s recommendations and transition to become Phase 3 ready. To our knowledge, Entera stands as the first osteoporosis drug development company ever permitted to conduct a single placebo controlled registrational study with a BMD (NOT fracture) endpoint. This is unprecedented and we believe, speaks to the agency’s partnership in this journey to find a viable treatment alternative to treat the millions of osteoporosis patients that, despite the guidelines and availability of highly efficacious anabolic agents, are simply unwilling to take the daily or monthly injections,” stated Miranda Toledano, Chief Executive Officer of Entera.