Oral teriparatide tablet (EB613) gets FDA nod for Phase 3 trial

@mayblin Do you know if that would involve the full dose and normal length of treatment for both?

@njx58 indeed!

For this study - Combined Anabolic Therapy (CAT):

Inclusion Criteria:

women aged 45+
postmenopausal
osteoporotic with high risk of fracture

Exclusion Criteria:

no significant previous use of bone health modifying treatments
known congenital or acquired bone disease other than osteoporosis
significant renal disease, liver disease, cardiopulmonary disease, or psychiatric disease
abnormal calcium or parathyroid hormone level
serum vitamin D <20 ng/dL
anemia (hematocrit <32%)
history of malignancy (except non-melanoma skin carcinoma)
excessive alcohol use or substance abuse
known contraindications to romosozumab or teriparatide

information provided by Dr. Benjamin Leder and is available on ClinicalTrials.gov ID NCT06558188

@tillymack
For Combined Anabolic Therapy (CAT) Phase 4 trial, fulll dose of romosoumab (210mg) and teriparatide (20mcg) will be used. Study duration: 12mo. 2 study groups: romosoumab vs romosozumab + teriparatide. Outcome measure will be L-spine Lumbar areal bone mineral density 12mo vs 0mo.

For oral teriparatide tablet (EB613), the chosen dosage hasn't been disclosed. Duration of the study will be 12mo, with "an open-label extension study to follow patients through 24 months to supplement EB613’s safety, durability of effect and sequence data"; and "primary endpoint of total hip bone mineral density (BMD) at Month 12".

@njx58 Teriparatide is the drug name for the brand-name Forteo. Not having to do an injection every day for 2 years, and keeping injectable teriparatide cool would be very helpful.

@kfhoz completely agree. If they can get the same results as the injection, with similar possible side effects, that's a definite improvement.

@mayblin Such good news about the possibility of an oral anabolic! I think the previous trial locations were all in Israel. Anyone on this forum located in Israel may want to watch out for the Phase 3 study.

The latest trial is listed as a Phase 1 study, so it is curious to me that they will jump to Phase 3 next.
Assess Safety and Compare PK of New Oral hPTH(1-34) Tablet Formulations vs. EBP05 Tablets and Subcutaneous Forteo https://clinicaltrials.gov/study/NCT05965167

Entera earlier appear to have done a Phase 2 trial on the EBP05 formulation that they then compared in the later trial that finished in early 2026.
A Six-month Phase 2 Study of Oral hPTH(1-34) (EBP05) in Postmenopausal Women With Low Bone Mass https://clinicaltrials.gov/study/NCT04003467

NOTE: The drug company has been working on oral PTH(1-34) formulations since before the Phase 2 study start date listed as 2019. And the drug still may fail for taking in oral form. It seems good sport to tilt at "big pharma" but bringing a new drug to market is very expensive and there is nobody else who will pay for a big study like the one planned. It seems as if the next study is also going to leverage the new osteoporosis treat-to-target FDA rules that allow BMD, instead of fracture reduction, to determine success. If the drug is successful then that will save many years of lead time in bringing it to market, although with the trade-off of more risks.
https://www.fda.gov/drugs/drug-safety-and-availability/fda-qualifies-total-hip-bone-mineral-density-bmd-surrogate-endpoint-osteoporosis-drug-development

@kfhoz thank you very much for the detailed info and thoughtful comments!

A few clarifications,

EBP05 and EB613 are the same drug. The Phase 2 trial (NCT04003467) was registered on ClinicalTrials.gov under the name "EBP05," but the published results of that same trial - same number of patients, same doses, same investigators - refer to the drug as "EB613." EBP05 was simply the earlier development name.

The Phase 1 study after Phase 2 isn't a step backward in this scenario. For a truly new drug (brand new chemical entity NCE), the standard path is Phase 1 → 2 → 3, where Phase 1 is the first-in-human study to establish basic safety and how the drug behaves in the body (pharmacology study). But 'Phase 1' also describes another kind of study - a bridging study. When a company modifies its tablet (changes in coating, absorption enhancers, excipients, or manufacturing process, etc.), regulators require a study to confirm the reformulated tablet delivers the drug into the bloodstream comparably to the original. This pharmacokinetic (PK) study is classified as Phase 1, but this doesn't mean the program is starting over. So the sequence here is logical: Phase 2 (original formulation, completed) → Phase 1 bridging study (new vs. old formulation, completed early 2026) → Phase 3 (trial with the optimized formulation).

What's particularly interesting from the Phase 2 data is that oral PTH(1-34), or EBP05/EB613, appeared to have a different BTM kinetic profile from the injected version - it simultaneously stimulated bone formation markers and suppressed bone resorption markers, whereas injected teriparatide increases both. If confirmed in Phase 3, this dual mechanism could be a meaningful clinical differentiator, in addition to the convenience advantage over injections.

Your point about the hip BMD surrogate endpoint is spot on, and thanks for the link. The FDA now accepts total hip BMD improvement as evidence the drug works, rather than requiring years of data showing fewer fractures. This could significantly shorten the path to approval, with the tradeoff being less long-term fracture data at the time of approval.

The Phase 3 trial is expected to be larger (~750 participants) and likely multinational, potentially including US sites - worth watching for anyone interested in participating.

@mayblin Do they know what it does to the quality of the bone?

@dvargo
According to the press release, a transiliac crest bone biopsy substudy in a subset of the ~750 participants in the Phase 3 trial is planned for histomorphometry. This is consistent with the pivotal studies of all other anabolic osteoporosis drugs, which also included bone biopsy substudies. Since the active drug - PTH(1-34) or teriparatide - is the same as in Forteo, the biopsy in Phase 3 will confirm whether oral administration also results in normal-quality bone, similar to what has been observed with the injectable form.

Very exciting development. Gives me hope for my own long-term planning of what comes next having dine oral bisphosphonates for years and with Evenity being the next plan.