Lewiecki, Edward Michael

Abstract Disclosure: E.M. Lewiecki: Amgen Inc, Radius Health, Inc. K. Tough DeSapri: Amgen Inc, Radius Health, Inc. S. Denning: Amgen Inc, Radius Health, Inc. S.T. Harris: Amgen Inc, Radius Health, Inc. J.G. Sfeir: None. Y. Wang: Radius Health, Inc. J.A. Chiodo: Radius Health, Inc. F. Cosman: Amgen Inc, Biocon, Curateq, Enterabio, Radius Health, Inc, Theramex, UCB. Objectives: Studies have shown that the sequence of osteoporosis (OP) treatment can affect clinical outcome measures and likelihood of attaining therapeutic targets. The aim of this descriptive study was to evaluate the long-term OP treatment patterns in US patients prescribed anabolic therapies (ie, abaloparatide [ABL], teriparatide [TPTD], romosozumab [ROMO]). Methods: Anonymized patient claims data from a subset of ICON’s Symphony Health Patient Source Integrated Dataverse database was utilized. Men and women, aged ≥50 years with at least one prescription claim for ABL, TPTD, or ROMO from May 1, 2019 to April 30, 2021 were included. The index date was the date of the first anabolic treatment claim. For study inclusion, patients were required to have medical and pharmacy record information from 5 years prior to the start of, and 1 year after discontinuation of, anabolic treatment. Patients with a history of anabolic therapy in the 5 years prior to the index date were excluded. Results: 42,400 patients (ABL, n=16,673; TPTD, n=19,575; ROMO, n=6152) were included, of which 80%–90% were women. Persistence rates were low for all anabolic therapies. Overall mean (standard deviation [SD]) duration was 6.5 (5.8), 6.2 (5.6), and 6.0 (4.5) months for the ABL, TPTD, and ROMO groups, respectively, with approximately 45% of patients in the ABL and TPTD groups and 40% of patients in the ROMO group receiving therapy for ≤3 months. Only 18% (ABL) and 17% (TPTD) of patients received over 12 months of anabolic treatment, and 27% of patients in the ROMO group received over 9 months of treatment. In the 5 years prior to anabolic therapy, 35% (ABL), 34% (TPTD), and 47% (ROMO) of patients had prior OP treatment, with the majority having received an oral bisphosphonate (ABL, 26%; TPTD, 25%; ROMO, 21%) for a mean (SD) treatment duration of 15.8 (13.7), 15.5 (13.3), and 16.6 (14.4) months, respectively. The second most prescribed prior therapy was denosumab (ABL, 7%; TPTD, 7%; ROMO, 24%). In the 12 months after anabolic therapy, only 21% of patients in the ABL and TPTD groups received subsequent OP medication, the majority with either denosumab (9%) or oral BP (9%), and 49% of patients treated with ROMO received subsequent treatment, most of which was with denosumab (36%). Conclusions: The pattern of prescriptions of anabolic therapy in US adults identifies significant gaps in the treatment of skeletal fragility. Despite current clinical practice guidelines, the mean duration of anabolic treatment was less than 7 months, and a large majority of patients did not receive subsequent OP prescription following anabolic therapy. Additional research is needed to understand and overcome the obstacles in applying standard of care practices. Further analyses will reveal the clinical outcomes of these treatment patterns. Presentation: Saturday, July 12, 2025

Abstract Disclosure: E.M. Lewiecki: Amgen Inc, Kyowa Kirin, Ultragenyx, Angitia, Radius Health, Inc, Ascendis. E. Kapoor: Fresenius Kabi USA Inc., Astellas Pharma, Estetra SRL, WellFound Inc., Exeltis. S. Hurtado: None. V.M. Navarro: Bayer, Inc. M. Torres: Bayer, Inc. J. Beau: Bayer, Inc. I. Gkioni: Syneos Health LLC (providing service to Bayer), AstraZeneca. K. Genga: Bayer, Inc.. Background: The neuropeptide substance-P and its receptor neurokinin-1 (SP-NK1R pathway) play a role in bone metabolism and remodelling. Pre-clinical evidence also points to a role of this pathway in energy homeostasis. NK-1R antagonists have been proposed as potential therapies in obesity and musculoskeletal disorders like osteoporosis. Elinzanetant (EZN) is a dual neurokinin-1 and -3 receptor antagonist in late-stage development for vasomotor symptoms (hot flashes) associated with menopause. This post hoc analysis evaluates potential benefits of EZN on the skeleton, body weight, and body composition in postmenopausal women. Methods: Data were gathered from exploratory endpoints of the 52-week (wk), placebo (PL)-controlled, OASIS-3 Phase 3 EZN efficacy and safety trial. Mean percentage (%) change in total bone mass (kg) (measured indirectly by bioelectrical impedance analysis at baseline (BL), wks 4, 8, 12, 18, 24, 36, 52); mean % change in bone mineral density (BMD, measured directly by dual-energy X-ray absorptiometry at BL, wks 24 and 52) in femoral neck, total hip, and lumbar spine; and mean % change in key bone turnover markers osteocalcin (OC) and procollagen 1N-terminal propeptide (P1NP) at BL, wks 4, 8, 12, 18, 24, 36, 52 were evaluated. Weight, body mass index (BMI: weight/height2), waist circumference (WC), fat mass index (FMI; fat mass/height2), lean mass index (LMI; lean mass/height2) and body water were measured to monitor body composition at BL and wks 4, 8, 12, 18, 24, 36, 52. A sub-analysis was performed based on FMI at baseline (FMI ≤9 normal fat mass; >9 excess fat mass). Descriptive statistics were used to evaluate all parameters and trends. Results: From BL to wk 52, increasing trends in bone mass were observed with EZN (mean [SD]: 2.81 [1.02] to 2.95 [1.96]) but not PL (mean [SD]: 2.87 [1.09] to 2.87 [1.13]). In parallel, lower BMD reductions were seen in EZN vs PL at all skeletal sites [EZN vs PL, mean % change from BL: femoral neck (0.00% vs -1.22%), total hip (-0.70% vs -1.37%), and lumbar spine (-0.57% vs -1.22%), with considerable variability in both groups (SD range 3.01 - 4.70)]. Lower levels of circulating OC and P1NP were consistently observed over 52 wks of EZN treatment, suggesting a lower rate of bone resorption with EZN vs PL. Trending reductions in weight, BMI, and WC, along with increases in LMI and body water were observed with EZN vs PL. Trends of higher LMI in patients with excess fat, or lower FMI in patients with normal fat at BL were observed with EZN, suggestive of a positive body re-composition with EZN. Conclusions: These data expand on EZN safety profile and further point to novel potential benefits for the skeleton and body composition of postmenopausal women. Further research is warranted to provide conclusive evidence of the benefits of EZN specifically in post-menopausal women with obesity/overweight status or osteoporosis. Sponsorship: Bayer U.S., Whippany, NJ, USA Presentation: Monday, July 14, 2025

Objective: The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPG). Methods: Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols. Results: The Executive Summary of this 2020 updated guideline contains 52 recommendations: 21 Grade A (40%), 24 Grade B (46%), 7 Grade C (14%), and no Grade D (0%). These detailed, evidence-based recommendations allow for nuance-based clinical decision-making that addresses multiple aspects of real-world care of patients. The evidence base presented in the subsequent Appendix provides relevant supporting information for the Executive Summary recommendations. This update contains 368 citations: 123 (33.5%) EL 1 (highest), 132 (36%) EL 2 (intermediate), 20 (5.5%) EL 3 (weak), and 93 (25%) EL 4 (lowest). New or updated topics in this CPG include: clarification of the diagnosis of osteoporosis, stratification of the patient according to high-risk and very high-risk features, a new dual action therapy option, and transitions from therapeutic options. Conclusion: This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of postmenopausal osteoporosis.