JERUSALEM, July 18, 2022 (GLOBE NEWSWIRE) -- Entera Bio Ltd. (NASDAQ: ENTX), a leader in the development of orally delivered peptides and therapeutic proteins, announced today the execution of the following key milestones:
- The U.S. Food and Drug Administration (FDA) has granted Entera’s request for a Type C Meeting based on the revised phase 3 registrational study for lead clinical asset, EB613 (oral formulation of PTH (1-34, teriparatide), as the first oral anabolic drug to treat post-menopausal women with osteoporosis. The meeting is expected in H2 2022
- Following its End of Phase 2 Meeting with the FDA, Entera designed the pivotal study for EB613 as an 18 month double blind placebo-controlled study, followed by a 6-month open label transition to alendronate for all patients
- The study’s primary endpoint employs the Foundation for the National Institutes of Health Bone Quality Program (FNIH BQP) total hip Bone Mineral Density (BMD) as a surrogate endpoint to evaluate fracture risk. FDA re-confirmed that with a well-designed BMD study, EB613 approval would not require a fracture study
- In line with her increased executive role since earlier this year, Ms. Miranda Toledano, Entera Board Member and industry veteran with over 20 years of experience succeeds Dr. Spiros Jamas as Chief Executive Officer
FDA Acceptance of Type C Meeting: Phase 3 Design of EB613 Under Review
During Entera’s End of Phase 2 Meeting, FDA’s Division of Endocrinology remarked on the FNIH BQP published meta-regression analysis which is based on patient-level BMD and fracture incidence data from more than 22 placebo-controlled fracture endpoint studies across all classes of osteoporosis drugs, including teriparatide. The FNIH BQP data indicate that changes in Total Hip BMD (in contrast to lumbar spine or femoral neck BMD measurements) provides a superior surrogate marker of an osteoporosis drug’s effects on vertebral, nonvertebral and all site fracture risk. The FNIH BQP BMD data and Surrogate Threshold Effects (STEs) are in the process of qualification by the FDA to become the first surrogate endpoint for fracture risk reduction1.
FDA suggested that Entera explore the FNIH BQP STEs and the design of a placebo-controlled study as an alternative to the originally contemplated non-inferiority design versus Forteo.® Entera has since submitted to the FDA, as part of its Type C briefing documents, a revised Phase 3 protocol. The study is expected to be an 18-month randomized, double-blind, multicenter study comparing the effects of oral PTH (1-34, teriparatide) EB613 vs. placebo on BMD in post-menopausal women with osteoporosis at high risk of fracture, followed by a 6-month open-label extension where all patients will be transitioned to alendronate, a standard of care anti-resorptive therapy.
1 Black DM et. al. The Lancet. Diabetes & Endocrinology 2020 Eastell R et. al. JBMR 2021FDA Approves Biomarker Qualification Plan for the First Surrogate Endpoint in Anti-Osteoporosis Drug Trials, June 1st, 2022, https://www.fnih.org/news/announcements/fda-approves-biomarkers-qualification-plan-first-surrogate-endpoint-anti
Patients will be randomized in a 2:1 ratio to receive blinded treatments with either EB613 (N=400) 2.5mg dose of oral PTH or Placebo (N=200). The 6-month extension phase of the study is intended to provide information on the transition from EB613 to a standard anti-resorptive therapy which has been shown to maintain or augment the increases in BMD following injectable PTH therapies, to preserve blinding of the prior therapy and to ensure that patients randomized to the placebo arm also receive an osteoporosis treatment.
The primary objective or endpoint of the phase 3 study will evaluate the effect of daily oral EB613 treatment on percent change in Total Hip BMD over 18 months versus placebo. Statistical methods will compare the observed treatment effect compared to pre-defined STEs associated with vertebral fracture, all site fracture and nonvertebral fracture risk reduction. The study will also look at secondary endpoints including changes in lumbar spine and femoral neck BMD and EB613’s effects on biochemical markers of bone formation and resorption.
“In the past months, Entera has invested a considerable amount of time aligning our proposed Phase 3 study with FDA’s EOP2 guidance, with the support of our clinical and statistical team, world-renowned scientific and clinical leaders in osteoporosis drug development, and representative institutional review boards. We are appreciative of FDA’s inputs and believe that the current Phase 3 design is a much de-risked pivotal study pathway and enables us to continue to study a similar patient population, based on T-Score and other criteria, as in our Phase 2 dose ranging study which met its 3-month biomarker and 6-month BMD endpoints. We look forward to providing updates to you on the outcome of our conversation with FDA later this year,” said Miranda Toledano, Entera’s Chief Executive Officer.
CEO Transition
Entera’s Board of Directors appointed Miranda Toledano as Chief Executive Officer (CEO) as of July 15th, 2022, succeeding Dr. Spiros Jamas.
Chairman of the Board Mr. Jerry Lieberman said, “The management transition reflects a strategic reorientation of Entera as we embark on pivotal clinical development and ongoing strategic discussions. I am thrilled to announce Miranda as our new CEO. Her fundamental understanding of Entera’s pipeline and transaction-focused track record in the industry is aligned to the current stage of the Company. Her contributions as an independent board member for the last 4 years also demonstrate her passion and commitment to establishing Entera as a leading biopharmaceutical entity. On behalf of Entera’s Board, we would like to recognize and thank Dr. Spiros Jamas for his contributions to Entera and advancement to success across our core programs.”
Ms. Toledano stated, “We are laser focused on unlocking the value of Entera’s oral delivery platform and core therapeutic assets. Both of our lead oral PTH drug candidates, EB613 for the treatment of osteoporosis and EB612 for the treatment of hypoparathyroidism are highly differentiated with the potential to meaningfully change the treatment paradigm and the lives of patients in their respective indications. I am excited to take on the challenge of leading Entera at this critical time and help the Company forge forward which is why I first took more executive responsibility a few months ago. We believe that Entera’s science has poised it as one of the leading entities in transforming the profile of therapeutic proteins to an oral route of administration. We further believe that this is especially valuable in chronically treated indications such as osteoporosis where most patients are under-treated because of the high cost and their reluctance to take injectable drugs. EB613 is positioned as a viable anabolic (bone formation) option to potentially lower the risk of fractures for a much wider population of post-menopausal osteoporotic women versus SC injected PTH drugs. We believe EB613 will deliver a tablet form (oral) PTH to fulfill the promise of this validated therapeutic class.”
Dr. Jamas said, “I’m very proud of the significant progress we made advancing Entera’s lead oral PTH asset, EB613 for the treatment of osteoporosis towards a pivotal Phase 3 study, including successfully completing the Phase 2 study. We demonstrated and presented data on the utility of Entera’s oral delivery platform with other peptides, filed IP on a new and improved oral delivery platform and strengthened the management team. I support this transition and have full confidence that the team will realize Entera’s full potential.”
Ms. Toledano has served as a Member of the Board of Directors at Entera since 2018, and as Member of the Scientific Advisory Committee since February 2022. In May 2022, she also joined as Entera’s Chief Business Officer and Chief Financial Officer. Previously, Miranda served as Chief Operating Officer, Chief Financial Officer, and Director of TRIGR Therapeutics, an oncology focused, clinical stage bispecific antibody company acquired by Compass Therapeutics (Nasdaq: CMPX) in June 2021 just 3 years after its establishment with her co-founder George Uy. At TRIGR, Miranda oversaw the clinical development of lead asset TR009 (now CTX-009) and led strategic execution, including a $117 million China License Transaction and acquisition by CMPX. Previously, Ms. Toledano served as Head of Healthcare Investment Banking at MLV & Co. (acquired by B. Riley FBR & Co.), where she completed biotech equity financings (IPOs, ATMs, and follow-ons) totaling over $4 billion in aggregate value. Earlier in her career, Ms. Toledano served as vice president in the investment group of Royalty Pharma. Ms. Toledano is also a member of the board of directors of Journey Medical (Nasdaq: DERM) and NEXGEL (Nasdaq: NXGL). Ms. Toledano holds a B.A. in Economics from Tufts University and an MBA in Finance and Entrepreneurship from the NYU Stern School of Business.
About EB613
Parathyroid hormone (PTH) is an 84-amino acid hormone and the primary regulator of calcium and phosphate metabolism in bone and kidney. EB613 is an oral formulation of synthetic hPTH (1-34), (teriparatide), a peptide consisting of the first 34 amino acids of PTH which represent the functional region. Subcutaneous Forteo® (teriparatide injection) has been the leading anabolic treatment of osteoporosis since 2002. EB613 utilizes Entera’s oral drug delivery platform which promotes enteric absorption and stabilizes teriparatide in the gastrointestinal tract. Entera’s Oral PTH formulations have been administered collectively to a total of 225 subjects in two Phase 1 studies and 3 phase 2 studies (including 35 in 2 phase 2 hypoparathyroidism studies). The most recent study was a dose ranging Phase 2 study in postmenopausal women with low bone mass. This study met primary and key secondary endpoints and was presented in a late-breaker oral presentation at the ASBMR 2021 conference. For the primary efficacy endpoint: a statistically significant increase in P1NP (a bone formation marker) at 3 months was achieved. A significant dose response was observed for 0.5, 1.0, 1.5 and 2.5 mg oral PTH doses on P1NP, Osteocalcin and bone mineral density (BMD). Subjects receiving the 2.5 mg dose of EB613 showed significant increases in dose-related BMD at the lumbar spine, total hip, and femoral neck at 6 months. Subjects receiving the 2.5 mg dose of EB613 daily for 6 months had a significant placebo adjusted increase of 3.78% in lumbar spine BMD (p