lasofoxifene topical (AZU-101) / Ligand, Azure Biotech - LARVOL DELTA

Proof of Concept Study of Vaginal AZU-101 in Vulvovaginal Atrophy in Postmenopausal Women (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Azure Biotech Inc. | Not yet recruiting ➔ Recruiting | Phase classification: P1/2 ➔ P2 | N=35 ➔ 90

Enrollment change • Enrollment open • Phase classification • Vaginal Atrophy • Women's Health

Open-Label Study of Vaginal AZU-101 in Postmenopausal Women (clinicaltrials.gov) - P1/2 | N=35 | Not yet recruiting | Sponsor: Azure Biotech Inc. | Trial completion date: Dec 2024 ➔ Jun 2027 | Trial primary completion date: Sep 2024 ➔ Dec 2026

Trial completion date • Trial primary completion date

ELAINE 3: Open-Label, Randomized, Multicenter, Phase 3 Study of the Efficacy and Safety of Lasofoxifene Plus Abemaciclib for Treating Locally Advanced or Metastatic, ER+/HER2–, Breast Cancer With an ESR1 Mutation (MBCC 2025) - P2, P3 | "The phase 2 ELAINE 1 trial (NCT03781063) showed numerically greater progression-free survival (PFS; median, 5.6 months vs 3.7 months; HR, 0.669; 95% CI, 0.445-1.125; P = .138), objective response rate (ORR, 13% vs 3%; P = .124), and clinical benefit rate (CBR, 37% vs 22%; P = .117) vs the ER degrader fulvestrant, with a favorable safety profile...Women (pre- and postmenopausal) and men were aged 18 years or older; and had ER+/HER2–, locally advanced breast cancer and/or metastatic breast cancer; 1 or more acquired ESR1 mutation; progression on an aromatase inhibitor plus palbociclib or ribociclib as their first hormonal therapy for advanced breast cancer/metastatic breast cancer; and 1 or fewer chemotherapy line in the advanced/ metastatic setting...Target sample size is up to 500 to provide 90% power with a 1-sided type I error rate of 0.025 after 285 PFS events. Status Recruitment has been initiated and is expected to occur over 18 months."

Clinical • Metastases • P3 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Effects of Lasofoxifene Versus Fulvestrant on Vaginal and Vulvar Symptoms in Patients With ESR1-Mutated, ER+/HER2-, Metastatic Breast Cancer From the ELAINE 1 Study. (PubMed, Clin Breast Cancer) - "Oral lasofoxifene (5 mg/day), but not fulvestrant, appears to improve GSM vaginal symptoms in women with mBC. These preliminary findings suggest further study is needed; such will be explored in the phase 3, registrational, ELAINE 3 trial in patients with ESR1-mutated, ER+/HER2- mBC."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Pain • Solid Tumor • Vaginal Atrophy • Women's Health • ER • HER-2

Oral lasofoxifene's effects on moderate to severe vaginal atrophy in postmenopausal women: two phase 3, randomized, controlled trials. (PubMed, Menopause) - "In two phase 3 trials, oral lasofoxifene 0.25 and 0.5 mg/d provided significant and clinically meaningful improvements in vaginal signs/symptoms with a favorable safety profile, suggesting beneficial effects of lasofoxifene on genitourinary syndrome of menopause."

Journal • P3 data • Vaginal Atrophy • Women's Health

An open-label, randomized, multi-center phase 2 study evaluating the activity of lasofoxifene relative to fulvestrant for the treatment of postmenopausal women with locally advanced or metastatic ER+/HER2 - breast cancer (MBC) with an ESR1 mutation (SABCS 2018) - "Agents targeting the ER pathway including aromatase inhibitors (AIs), fulvestrant and tamoxifen along with CDK 4/6 inhibitors are considered standard for first and 2nd line treatment. It is assumed that lasofoxifene will double the median PFS compared to fulvestrant in this ESR1 mutation patient population for a hazard ratio 0.5 and a power of 89% to reach a 1-sided p of <0.05.The study will commence in 4Q2018 and will complete recruitment in 1 year. It is anticipated that 25-30 centers in the US will be participating. "

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

[VIRTUAL] Effects of SERMs on Bone Health in Postmenopausal Women (ISGE-I 2020) - "Methods PubMed was searched for journal articles published in English using keywords of raloxifene (RLX), bazedoxifene (BAZ), ospemifene (OSP), or lasofoxifene (LAS), and bone. J Bone Miner Metab. 2006;24:314-318."

Clinical • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology • Vaginal Atrophy

[VIRTUAL] The challenge of SERMs (ISGE-I 2020) - "The SERMs assessed appear to have antiestrogenic or neutral effects on the breast; Tamoxifen, Raloxifene, and Lasofoxifene have shown antiestrogenic effects in clinical trials; and Bazedoxifene and Ospemifene have shown antiestrogenic effects in preclinical trials but appear to be neutral in clinical trials to date...Another interesting concept would be TSEC, a combination of Bazedoxifene with conjugated Estrogens...There is no breast or endometrial stimulation with treatment, and cardiovascular risk is not increased, and may be an alternative to HT. The rapid developments in molecular biology incorporates enormous possibilities on molecular biology, stem cells, cell biology in concurrence with genomics, functional genomics, genetics, proteomics, makes us optimistic, about the future of different estrogen modulators in not too long term in term."

Cardiovascular • Vaginal Atrophy • Venous Thromboembolism

Beyond estrogen: advances in tissue selective estrogen complexes and selective estrogen receptor modulators. (PubMed, Climacteric) - "Tamoxifen is an anti-estrogen in the breast used for treatment and prevention of breast cancer, with estrogen agonist activity in the uterus. Raloxifene prevents and treats osteoporosis and prevents breast cancer, and can be safely combined with vaginal but not systemic estrogen...Ospemifene is approved to treat dyspareunia, with potential benefits on bone and the breast, while lasofoxifene is being developed to treat resistant estrogen receptor-positive breast cancer in women. Estetrol is an estrogen synthesized exclusively during pregnancy by the human fetal liver and initially considered a weak estrogen, but it appears to have dual weak estrogenic/anti-estrogenic features."

Journal • Breast Cancer • Endometrial Cancer • Estrogen Receptor Positive Breast Cancer • Gynecologic Cancers • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Metabolic Disorders • Oncology • Osteoporosis • Solid Tumor • Uterine Cancer

The challenge of SERMs (ISGE 2020) - "The SERMs assessed appear to have antiestrogenic or neutral effects on the breast; Tamoxifen, Raloxifene, and Lasofoxifene have shown antiestrogenic effects in clinical trials; and Bazedoxifene and Ospemifene have shown antiestrogenic effects in preclinical trials but appear to be neutral in clinical trials to date...Another interesting concept would be TSEC, a combination of Bazedoxifene with conjugated Estrogens...There is no breast or endometrial stimulation with treatment, and cardiovascular risk is not increased, and may be an alternative to HT. The rapid developments in molecular biology incorporates enormous possibilities on molecular biology, stem cells, cell biology in concurrence with genomics, functional genomics, genetics, proteomics, makes us optimistic, about the future of different estrogen modulators in not too long term in term."