Entera Bio Receives FDA Agreement on BMD as Primary Endpoint for EB613 Registrational, Phase 3 Study in Post-Menopausal Women with Osteoporosis
Entera Bio (NASDAQ: ENTX) has received FDA agreement on using Bone Mineral Density (BMD) as the primary endpoint for its Phase 3 study of EB613, an oral treatment for post-menopausal osteoporosis. The FDA approved a 24-month phase 3 study design where total hip BMD will be the primary endpoint, with vertebral fractures as a secondary endpoint.
This represents a significant shift from traditional osteoporosis drug trials that required fracture incidence as the primary endpoint. The development aims to create the first oral, once-daily anabolic tablet for osteoporosis treatment, addressing a market of over 200 million women globally who suffer from the condition.
Entera Bio (NASDAQ: ENTX) ha ottenuto l'approvazione della FDA per l'utilizzo della Densità Minerale Ossea (BMD) come endpoint primario nel suo studio di Fase 3 su EB613, un trattamento orale per l'osteoporosi post-menopausale. La FDA ha approvato un protocollo di studio di fase 3 della durata di 24 mesi in cui la BMD dell'anca totale sarà l'endpoint principale, mentre le fratture vertebrali rappresenteranno un endpoint secondario.
Questo rappresenta un cambiamento significativo rispetto ai tradizionali studi sui farmaci per l'osteoporosi, che richiedevano l'incidenza delle fratture come endpoint primario. Lo sviluppo punta a creare la prima compressa anabolica orale da assumere una volta al giorno per il trattamento dell'osteoporosi, rivolgendosi a un mercato di oltre 200 milioni di donne nel mondo affette da questa patologia.
Entera Bio (NASDAQ: ENTX) ha recibido la aprobación de la FDA para usar la Densidad Mineral Ósea (BMD) como el endpoint principal en su estudio de Fase 3 de EB613, un tratamiento oral para la osteoporosis posmenopáusica. La FDA aprobó un diseño de estudio de fase 3 de 24 meses donde la BMD total de cadera será el endpoint principal, y las fracturas vertebrales serán un endpoint secundario.
Esto representa un cambio significativo respecto a los ensayos tradicionales de medicamentos para la osteoporosis, que requerían la incidencia de fracturas como endpoint principal. El desarrollo busca crear la primera tableta anabólica oral de una vez al día para el tratamiento de la osteoporosis, dirigido a un mercado de más de 200 millones de mujeres en todo el mundo que padecen esta condición.
Entera Bio (NASDAQ: ENTX)는 폐경 후 골다공증 치료제인 EB613의 3상 시험에서 골밀도(BMD)를 주요 평가 지표로 사용하는 것에 대해 FDA의 승인을 받았습니다. FDA는 총 고관절 BMD를 주요 평가 지표로 하고 척추 골절을 부차적 평가 지표로 하는 24개월 3상 시험 설계을 승인했습니다.
이는 기존 골다공증 약물 시험에서 골절 발생을 주요 평가 지표로 요구하던 것에서 큰 변화를 의미합니다. 이번 개발은 전 세계 2억 명 이상의 여성이 앓고 있는 골다공증 치료를 위해 하루 한 번 복용하는 최초의 경구용 동화작용제 정제를 만드는 것을 목표로 합니다.
Entera Bio (NASDAQ: ENTX) a obtenu l'accord de la FDA pour utiliser la densité minérale osseuse (BMD) comme critère principal dans son étude de phase 3 sur EB613, un traitement oral de l'ostéoporose post-ménopausique. La FDA a approuvé un protocole d'étude de phase 3 de 24 mois où la BMD totale de la hanche sera le critère principal, avec les fractures vertébrales comme critère secondaire.
Cela représente un changement important par rapport aux essais traditionnels de médicaments contre l'ostéoporose, qui exigeaient l'incidence des fractures comme critère principal. Ce développement vise à créer le premier comprimé anabolique oral à prise quotidienne pour le traitement de l'ostéoporose, ciblant un marché de plus de 200 millions de femmes dans le monde souffrant de cette maladie.
Entera Bio (NASDAQ: ENTX) hat von der FDA die Zustimmung erhalten, die Knochendichte (BMD) als primären Endpunkt für seine Phase-3-Studie zu EB613, einer oralen Behandlung der postmenopausalen Osteoporose, zu verwenden. Die FDA genehmigte ein 24-monatiges Phase-3-Studien-Design, bei dem die Gesamthüft-BMD der primäre Endpunkt und Wirbelfrakturen der sekundäre Endpunkt sind.
Dies stellt eine bedeutende Abweichung von traditionellen Osteoporose-Studien dar, die die Frakturhäufigkeit als primären Endpunkt verlangten. Die Entwicklung zielt darauf ab, die erste orale, einmal täglich einzunehmende anabole Tablette zur Osteoporosebehandlung zu schaffen und adressiert einen Markt von über 200 Millionen Frauen weltweit, die an dieser Erkrankung leiden.
- None.
- 24-month study duration indicates long timeline to potential approval
- No new osteoporosis drugs approved by FDA since 2019 shows regulatory challenges
Insights
FDA's acceptance of BMD as primary endpoint represents major regulatory breakthrough for Entera's osteoporosis drug development, potentially accelerating approval pathway.
This FDA agreement represents a significant regulatory breakthrough for Entera Bio's EB613 development program. The FDA's acceptance of total hip BMD (Bone Mineral Density) as a primary endpoint, rather than fracture incidence, marks a substantial deviation from historical precedent in osteoporosis drug development. This change could dramatically reduce the time, cost, and complexity of bringing EB613 to market.
Traditionally, new osteoporosis treatments face enormous hurdles requiring large-scale fracture endpoint trials that can involve thousands of patients, take many years, and cost hundreds of millions. These studies are not only resource-intensive but raise ethical concerns about withholding active treatment from high-risk patients in placebo groups.
By accepting BMD as the primary endpoint (with fractures as a secondary endpoint), the FDA is acknowledging strong surrogate marker validity between BMD improvements and fracture risk reduction. This regulatory flexibility likely stems from both the robustness of Entera's existing data and broader initiatives like SABRE (Study to Advance Bone Mineral Density as a Regulatory Endpoint).
The importance extends beyond just Entera - this precedent could reinvigorate innovation in the osteoporosis field, which has seen minimal new drug approvals in recent years partly due to these challenging regulatory requirements. For Entera specifically, this agreement provides a clearer, more efficient path to potentially bringing the first oral anabolic (bone-forming) treatment to a massive patient population with high unmet need.
JERUSALEM, July 28, 2025 (GLOBE NEWSWIRE) -- Entera Bio Ltd. (NASDAQ: ENTX), a leader in the development of oral peptides and protein replacement therapies, announced today that in a written response to a Type A meeting request, the U.S. Food and Drug Administration (FDA) agreed with the Company’s proposal that the NDA marketing application filing for EB613 would be supported by a single multinational, randomized, double-blind, placebo-controlled, 24 month phase 3 study in women with postmenopausal osteoporosis, where change in total hip BMD is evaluated as the primary endpoint, and incidence of new or worsening vertebral fractures is evaluated as the key secondary endpoint. This marks a shift from precedent placebo-controlled phase 3 studies of new osteoporosis drugs which required incidence of fracture as the primary endpoint.
“This regulatory update is a major milestone for Entera and the entire osteoporosis community,” said Miranda Toledano, CEO of Entera. “Our alignment with the FDA reflects the strength of our data and collaborative discussions. Importantly, it allows us to advance our clinical development program without having to wait for FDA’s qualification of the Study to Advance Bone Mineral Density as a Regulatory Endpoint (SABRE), which is still expected this year. We thank the FDA and the Review Team at the Division of Endocrinology for their constructive approach. We also thank the SABRE team for paving the path to innovation for osteoporosis treatment,” said Toledano.
“Osteoporosis afflicts more women than heart attack, stroke and breast cancer combined. Over 200 million women globally are estimated to have osteoporosis and remain vastly undertreated, despite efficacious injectable anabolic (bone forming) treatments. One in two women over the age of 50 will suffer a fracture due to osteoporosis. No new drug for osteoporosis has been approved by FDA since 2019; and innovation has stalled for close to a decade due to the size, duration, cost and ethical constraints associated with fracture endpoint studies. In a silent disease, patient and clinician access to novel and alternative forms of validated mechanisms of action is important. We are developing EB613 as the first oral, once-daily anabolic tablet treatment to potentially serve this unmet medical need. EB613 is intended to increase skeletal mass, improve bone microarchitecture and reduce the risk of fracture,” said Miranda Toledano, CEO of Entera.
About EB613
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. EB613 (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. Further abstracts have been submitted to ASBMR and NAMS 2025 conferences.
About Entera Bio
Entera is a clinical stage company focused on developing oral peptide and protein replacement therapies for significant unmet medical needs where an oral tablet form holds the potential to transform the standard of care. The Company leverages on a disruptive and proprietary technology platform (N-Tab™) and its pipeline of first-in-class oral peptide programs targeting PTH(1-34), GLP-1 and GLP-2. The Company’s most advanced product candidate, EB613 (oral PTH(1-34), teriparatide), is being developed as the first oral, osteoanabolic (bone building) once-daily tablet treatment for post-menopausal women with low BMD and high-risk osteoporosis. A placebo-controlled, dose-ranging Phase 2 study of EB613 tablets (n= 161) met primary (PD/bone turnover biomarker) and secondary endpoints (BMD). The EB612 program is being developed as the first oral PTH(1-34) tablet peptide replacement therapy for hypoparathyroidism. Entera is also developing the first oral oxyntomodulin, a dual targeted GLP1/glucagon peptide, in tablet form for the treatment of obesity and metabolic syndromes; and first oral GLP-2 peptide as an injection-free alternative for patients suffering from rare malabsorption conditions such as short bowel syndrome in collaboration with OPKO Health. For more information on Entera Bio, visit www.enterabio.com or follow us on LinkedIn, Twitter, Facebook, Instagram.
About SABRE
The Study to Advance BMD as a Regulatory Endpoint (SABRE) initiative, which started as a public private partnership sponsored by the FNIH in 2013, has amassed the strongest evidence to date that treatment-related gains in Bone Mineral Density (BMD) reliably and quantitatively predict fracture-risk reduction. In November 2023, the SABRE team submitted a full qualification package to FDA’s Biomarker Division as part of the Drug Development Tool Biomarker Qualification Pathway to potentially qualify BMD as a surrogate endpoint to fracture; in March 2024, the FDA Biomarker Division indicated to the SABRE project team that a decision would be issued within 10 months. The single most important predictor of osteoporotic fractures in postmenopausal women without a previous fracture is BMD. Treatment guidelines in the U.S. strongly recommend pharmacologic therapy for patients with a BMD T-score of -2.5 or lower in the spine, femoral neck, total hip. SABRE final FQP meta-analysis included data from 22 randomized, placebo-controlled trials (63,000 participants across seven drug classes) and showed that treatment-related gains in total-hip BMD explain
Cautionary Statement Regarding Forward Looking Statements
Various statements in this presentation are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements (other than statements of historical facts) in this presentation 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 the interpretation of clinical data; results of our clinical trials; the FDA’s interpretation and review of our results from and analysis of our clinical trials; 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; impacts to research and development or clinical activities that Entera may be contractually obligated to provide; overall regulatory timelines; the size and growth of the potential markets for our product candidates; the scope, progress and costs of developing Entera’s product candidates; Entera’s reliance on third parties to conduct its clinical trials; Entera’s ability to establish and maintain development and commercialization collaborations; Entera’s operation as a development stage company with limited operating history; Entera’s competitive position with respect to other products on the market or in development for the treatment of osteoporosis, hypoparathyroidism, short bowel syndrome, obesity, metabolic conditions and other disease categories it pursues; Entera’s ability to continue as a going concern absent access to sources of liquidity; Entera’s ability to obtain and maintain regulatory approval for any of its product candidates; Entera’s ability to comply with Nasdaq’s minimum listing standards and other matters related to compliance with the requirements of being a public company in the United States; Entera’s intellectual property position and its ability to protect its intellectual property; and other factors that are described in the “Cautionary Statement Regarding Forward-Looking Statements,” “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections of Entera’s most recent Annual Report on Form 10-K filed with the SEC, as well as Entera’s subsequently filed Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. There can be no assurance that the actual results or developments anticipated by Entera will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, Entera. Therefore, no assurance can be given that the outcomes stated or implied in such forward-looking statements and estimates will be achieved. Entera cautions investors not to rely on the forward-looking statements Entera makes in this presentation. The information in this presentation is provided only as of the date of this presentation, and Entera undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, except to the extent required by law.
Contact: Entera Bio: Ms. Miranda Toledano Chief Executive Officer Entera Bio Email: miranda@enterabio.com
FAQ
What did the FDA agree to for Entera Bio's (ENTX) EB613 Phase 3 trial?
How long will Entera Bio's (ENTX) Phase 3 trial for EB613 last?
What makes Entera Bio's EB613 different from other osteoporosis treatments?
How many women are affected by osteoporosis globally?
When was the last new osteoporosis drug approved by the FDA?
