bazedoxifene (BAZE-X1) / Oxygen Biotech - LARVOL DELTA

Overcoming challenges in conducting early phase breast cancer prevention trials: Bazedoxifene and conjugated estrogens vs waitlist control. (PubMed, Contemp Clin Trials) - P2 | "Despite a late start, accrual is likely to be completed within the funding period. NCT04821141."

Journal • Breast Cancer • Infectious Disease • Novel Coronavirus Disease • Oncology • Osteoporosis • Rheumatology • Solid Tumor

An in-silico scaffold- hopping approach to design novel inhibitors against gp130: A potential therapeutic application in cancer and Covid-19. (PubMed, Mol Divers) - "The two lead candidates show a better therapeutic profile in comparison to the two existing drugs- bazedoxifene and raloxifene. Both these potential leads can be addressed for their activity in-vitro and can be used as a potential anti-cancer treatment as well as to combat Covid-19 related cytokine storm."

Journal • Infectious Disease • Novel Coronavirus Disease • Oncology

ReWRAP (Remyelination for Women at Risk of Axonal Loss and Progression): Protocol and Baseline Characteristics of a Phase II Randomized Placebo-Controlled Delayed-Start Trial of Bazedoxifene for Myelin Repair Undergoing Enrollment (MSMilan 2023) - P2 | "BZA has strong preclinical effects on myelin repair, and in the general population demonstrated clinical benefits in treating postmenopausal osteoporosis. Together, these findings support the rationale for an RCT testing BZA in women with MS, evaluating established neuroimaging and neurovisual measures of myelin repair. Additionally, to support research in remyelination, novel digital tools could increase sensitivity to change and inform the duration and design of future clinical trials."

Clinical • P2 data • CNS Disorders • Infectious Disease • Multiple Sclerosis • Novel Coronavirus Disease • Osteoporosis • Rheumatology

Benzimidazole compound abrogates SARS-COV-2 receptor-binding domain (RBD)/ACE2 interaction In vitro. (PubMed, Microb Pathog) - "Molecular dynamics simulation of RBD/ACE2 in the presence BAZ resulted in loss of contact and specific hydrogen-bond interaction required for RBD/ACE2 stability. Taken together, these findings identified benzimidazole scaffold as a building block for developing novel RBD/ACE2 complex inhibitor and provided mechanistic basis for the use of bazedoxifene as a repurposable drug for the treatment of COVID-19 acting at RBD/ACE2 interface."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Hormone replacement therapy (conjugated oestrogens plus bazedoxifene) for post-menopausal women with symptomatic hand osteoarthritis: primary report from the HOPE-e randomised, placebo-controlled, feasibility study. (PubMed, Lancet Rheumatol) - "This outcome indicates that a full trial of an HRT in this population is feasible and acceptable and identifies potential refinements with regard to the design of such a trial. Research for Patient Benefit programme, National Institute for Health Research."

Journal • Immunology • Infectious Disease • Musculoskeletal Pain • Novel Coronavirus Disease • Osteoarthritis • Pain • Rheumatology

Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor–Positive Breast Cancer (Clin Cancer Res) - P1/2 | N=36 | NCT02448771 | "The study met its primary endpoint, with a clinical benefit rate of 33.3%, and the safety profile was consistent with what has previously been seen with palbociclib monotherapy. The median progression-free survival (PFS) was 3.6 months [95% confidence interval (CI), 2.0–7.2]. An activating PIK3CA mutation at baseline was associated with a shorter PFS (HR = 4.4; 95% CI, 1.5–13; P = 0.0026), but activating ESR1 mutations did not impact the PFS....The combination of palbociclib and bazedoxifene has clinical efficacy and an acceptable safety profile in a heavily pretreated patient population with advanced HR+/HER2− breast cancer."

P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Clinical Efficacy and Whole Exome Sequencing of Liquid Biopsies in a Phase IB/II study of Bazedoxifene and Palbociclib in Hormone Receptor-Positive Breast Cancer (Clin Cancer Res) - P1/2 | N=36 | NCT02448771 | "The study met its primary endpoint, with a clinical benefit rate of 33.3%, and the safety profile was consistent with what has previously been seen with palbociclib monotherapy. The median progression free survival (PFS) was 3.6 months (CI95% 2.0-7.2). An activating PIK3CA mutation at baseline was associated with a shorter PFS (HR = 4.4, CI95% 1.5-13, P = 0.0026) but activating ESR1 mutations did not impact the PFS....The combination of palbocilib and bazedoxifene has clinical efficacy and an acceptable safety profile in a heavily pre-treated patient population with advanced HR+/HER2- breast cancer."

P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Antiviral efficacy of selective estrogen receptor modulators against SARS-CoV-2 infection in vitro and in vivo reveals bazedoxifene acetate as an entry inhibitor. (PubMed, J Med Virol) - "Clomifene citrate, tamoxifen, toremifene citrate, and bazedoxifene acetate reduced the weight loss of hamsters challenged with SARS-CoV-2, and reduced hamster pulmonary viral load and IL-6 expression when assayed at 4 days post-infection. And, bazedoxifene acetate inhibited pseudoviruses infection of original SARS-CoV-2, Delta variant, Omicron variant and SARS-CoV. These results offer critical information supporting bazedoxifene acetate as a promising agent against coronaviruses."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IL6

Hand Osteoarthritis: investigating Pain Effects in a randomised placebo-controlled feasibility study of estrogen-containing therapy (HOPE-e): report on the primary feasibility outcomes (EULAR 2022) - "The licensed HRT Duavive (conjugated estrogens + SERM bazedoxifene) was selected on its potential for efficacy and tolerability... Despite COVID-19 and a reduced recruitment period, this study recruited sufficient numbers to assess feasibility outcomes. Randomisation of eligible people and retention rates were high. A mixture of remote and face to face visits due to COVID-19 probably improved recruitment and retention and was supported by participants, who were generally satisfied with the study design and medication."

Clinical • Immunology • Infectious Disease • Musculoskeletal Pain • Novel Coronavirus Disease • Osteoarthritis • Pain • Rheumatology

Post-fracture Medication and Mortality (clinicaltrials.gov) - P=N/A | N=216155 | Completed | Sponsor: National Cheng-Kung University Hospital

New trial • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology