- 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
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.
FDA Approves Biomarker Qualification Plan for the First Surrogate Endpoint in Anti-Osteoporosis Drug Trials,
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
CEO Transition
Entera’s Board of Directors appointed
Chairman of the Board Mr.
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<0.008) which is similar to the 3.9% increase in lumbar spine BMD seen with Forteo® in clinical studies reported in the literature2. Increases in total hip and femoral neck BMD were greater than those previously reported with Forteo®. EB613 exhibited an excellent safety profile, with no drug related serious adverse events. The most common adverse events included mild nausea, moderate back pain, moderate headache, and moderate upper abdominal pain.
2Leder BZ et.al. JCEM 2015
About
Entera is a leader in the development of orally delivered large molecule therapeutics for use in areas with significant unmet medical need where adoption of injectable therapies is limited due to cost, convenience and compliance challenges for patients. The Company’s proprietary, oral drug delivery technology is designed to address the technical challenges of poor absorption, high variability, and the inability to deliver large molecules to the targeted location in the body through the use of a synthetic absorption enhancer to facilitate the absorption of large molecules, and protease inhibitors to prevent enzymatic degradation and support delivery to targeted tissues. The Company’s most advanced product candidates, EB613 for the treatment of osteoporosis and EB612 for the treatment of hypoparathyroidism are in clinical development. The Company recently completed the phase 2 study for EB613. Entera also licenses its technology to biopharmaceutical companies for use with their proprietary compounds and, to date, has established a collaboration with Amgen Inc. For more information on
Cautionary Statement Regarding Forward Looking Statements
Various statements in this press release are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 (PSLRA). All statements (other than statements of historical facts) in this press release regarding our prospects, plans, financial position, business strategy and expected financial and operational results may constitute forward-looking statements. Words such as, but not limited to, “anticipate,” “believe,” “can,” “could,” “expect,” “estimate,” “design,” “goal,” “intend,” “may,” “might,” “objective,” “plan,” “predict,” “project,” “target,” “likely,” “should,” “will,” and “would,” or the negative of these terms and similar expressions or words, identify forward-looking statements. Forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. Forward-looking statements should not be read as a guarantee of future performance or results and may not be accurate indications of when such performance or results will be achieved.
Important factors that could cause actual results to differ materially from those reflected in Entera’s forward-looking statements include, among others: changes in our interpretation of the 3-month biomarker data from the Phase 2 clinical trial of EB613, the timing of data readouts from the Phase 2 clinical trial of EB613, the full results of the Phase 2 clinical trial of EB613 and our analysis of those full results, the FDA’s interpretation and review of our results from and analysis of our Phase 2 trial of EB613, unexpected changes in our ongoing and planned preclinical development and clinical trials, the timing of and our ability to make regulatory filings and obtain and maintain regulatory approvals for our product candidates; the potential disruption and delay of manufacturing supply chains, loss of available workforce resources, either by Entera or its collaboration and laboratory partners, due to travel restrictions, lay-offs or forced closures or repurposing of hospital facilities; impacts to research and development or clinical activities that Entera is contractually obligated to provide, such as those pursuant to Entera’s agreement with Amgen; overall regulatory timelines, if the FDA or other authorities are closed for prolonged periods, choose to allocate resources to review of COVID-19 related drugs or believe that the amount of Phase 2 clinical data collected are insufficient to initiate a Phase 3 trial, or a meaningful deterioration of the current political, legal and regulatory situation in
Contact:Entera Bio : Ms.Miranda Toledano Chief Executive OfficerEntera Bio Email: miranda@enterabio.com Phone: +972-58-55-88-470 IR: Mr.Christopher M. Calabrese Managing DirectorLifeSci Advisors LLC Email: ccalabrese@lifesciadvisors.com Phone: (917) 680-5608
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