Benzinga | Oct 6, 2021 08:32AM EDT

Entera Bio Presents Phase 2 6-Month Bone MIneral Density Data For Oral PTH Formulation At Late Breaker ASBMR Conference Session; Says Linear Dose Responses Seen; Says Pivotal Phase 3 Registration Study Expected To Commence In 2022

Entera Bio Ltd. (NASDAQ:ENTX), a leader in the development of orally delivered large molecule therapeutics, presented the 6-month bone mineral density (BMD) data from its completed Phase 2 clinical trial of EB613, an oral formulation of human parathyroid hormone (1-34), or PTH, for the treatment of osteoporosis. The Late Breaking Presentation "A Six-month Phase 2 Study of Oral PTH in Postmenopausal Women with Low Bone Mass -- 6 Month Bone Mineral Density (BMD) Results" was selected for a prestigious oral presentation, given by Entera's Chief Medical Officer, Dr. Arthur Santora. The oral presentation was given at 12:15 PM PDT at the American Society for Bone and Mineral Research (ASBMR) Annual Meeting in San Diego on Monday, October 4, 2021. Many scientific leaders in the field of Osteoporosis expressed great excitement with the data and the possibility of an oral osteoanabolic (bone building) agent which elderly osteoporosis patients would be willing to take.

This Phase 2 Dose Ranging study in Osteoporosis showed clinically significant changes in increases in BMD at the spine, femoral neck, and total hip. These BMD changes were associated with an increase in P1NP and a decrease in the serum CTX biomarker. A difference between the increase in P1NP, a marker of bone formation and the change in CTX, a marker of bone resorption, usually indicates an increase in bone mass, and is sometimes referred to as an "anabolic window."

Key secondary endpoints for the trial included changes in lumbar spine, femoral neck and total hip BMD, the bone markers P1NP, osteocalcin and serum CTX after 6 months of treatment.

The most important secondary objective in the study was the demonstration of a statistically significant increase in BMD of the lumbar spine. Patients receiving 2.5 mg oral PTH for 6 months had a placebo-adjusted increase of 3.78% in lumbar spine (LS) BMD (p<0.002). Additionally, there was a highly statistically significant dose dependent increase in LS BMD across all dose groups (p<0.0001). In previously published studies with subcutaneous injectable PTH(1-34) (Forteo(r)) no significant increases in BMD of the total hip and or the femoral neck were generally observed at 6 months. In contrast, EB613 showed dose-dependent increases in BMD at the total hip and femoral neck at 6 months, with the greatest increases in BMD observed in the 2.5 mg group. The increase in BMD at these sites has great clinical relevance as a high percent of osteoporotic fractures occur at the hip.

"We are really excited by these full 6-month BMD data which show that our oral PTH 1-34 (EB613) for the treatment of osteoporosis produced results comparable with results observed in previously published studies utilizing injectable PTH 1-34 (Forteo(r))," stated Entera CEO Dr. Spiros Jamas. "The data provides an excellent foundation for our Phase 3 registration trial, which we expect to commence in 2022." He noted that there is an enormous clinical need for an oral agent to treat osteoporosis which can build bone and thereby reverse some of the decrease in bone strength caused by Osteoporosis. EB613 addresses this need.

Dr. Santora noted, "In this study, EB613 demonstrated reliable, consistent improvements in spine and hip BMD, overcoming a major challenge of earlier efforts to develop oral PTH agents. Additionally, EB613 performed comparably to injectable PTH 1-34 for increases in lumbar spine BMD, and also showed significant increases of BMD at the femoral neck and total hip. Change in BMD is the efficacy endpoint required for a 505(b)(2) approval pathway. Interestingly, a decrease in CTX, a marker of bone resorption, was robust and continued through six months. This contrasts with the large CTX increase typically observed with injectable formulations of PTH 1-34 currently available and may reflect a favorably lower bone remodeling rate with EB613."

The safety profile of EB613 was consistent with the known profile of subcutaneous PTH. The most common drug-related AEs were headache, nausea, dizziness and presyncope; all drug-related adverse events were either mild or moderate, and there were no serious drug-related AE. There were no treatment-emergent hypercalcemia AEs.

Osteoporosis, characterized by low bone mass and deterioration of bone tissue, leads to decreased bone strength and increased risk of fracture. EB613, an oral PTH, may address a major unmet clinical need for formulations that may facilitate treatment in high-risk patients who may not be willing to use daily or monthly injectable osteoanabolic therapeutics.

Phase 2 Six-Month Study Design and Results

Entera's Phase 2, 6-month, dose-ranging, placebo-controlled study evaluated EB613 in 161 postmenopausal women with low BMD. Subjects in the 2.5 mg group were either treated with 2.5 mg from Day 1 or titrated to 2.5 mg over 2 months. The primary endpoint of change in P1NP at 3 months was met and previously announced by Entera. The key secondary efficacy objective was the change in lumbar spine BMD vs. placebo at 6 months. Changes in biomarkers of bone turnover and change in proximal femoral BMD were evaluated through 6 months.

Six-month BMD and biomarker data are summarized below:

* Significant and dose-dependent increases in BMD of the lower spine, total hip, and femoral neck at 6 months (all p <0.01), with the greatest increases in the 2.5 mg EB613 treated group

* Subjects receiving 2.5 mg EB613 for 6 months had a placebo-adjusted increase of 3.78% in lower spine BMD (p<0.008); this group combined with the titrated 2.5 mg group showed lower spine BMD increase of 2.73% (p<0.002)

* Pooled 2.5 mg EB613 group had significant placebo-adjusted 2.76% increase in femoral neck (p<0.002) and a 1.84% increase in total hip BMD (p<0.02) at 6 months. Significant decrease in serum CTX (of 21% from baseline at 6 months (P <0.01) while P1NP was unchanged The safety profile of EB613 was consistent with and similar to the known profile of injectable PTH (Forteo(r))E