vilaprisan (BAY 1002670) / Bayer - LARVOL DELTA

Progesterone signaling in uterine fibroids: Molecular mechanisms and therapeutic opportunities. (PubMed, Life Sci) - "Clinical trials have demonstrated the effectiveness of SPRMs like mifepristone, asoprisnil, and ulipristal acetate in reducing fibroid size and symptoms, though concerns about safety, particularly with long-term use, remain. Newer SPRMs, such as vilaprisan, show promise, but further research is necessary to assess the long-term safety and effectiveness. This review discusses the mechanisms by which progesterone contributes to fibroid growth and examines clinical effectiveness of SPRMs as potential treatments for uterine fibroids."

Journal • Review • Gynecology • Oncology • Solid Tumor • Uterine Leiomyoma • Women's Health • PGR

Selective progesterone receptor modulators for the treatment of dysmenorrhea: an update. (PubMed, Expert Opin Pharmacother) - "The present review examines the development of the clinical trials and observational studies done with the different SPRMs for the treatment of dysmenorrhea in patients with uterine diseases. Mifepristone, telapristone acetate and vilaprisan have antagonistic activity on PRs, while ulipristal acetate and asoprisnil have both potent antagonist and partial agonist effects.While no studies have been done on primary dysmenorrhea, the different SPRMs have been studied in the treatment of endometriosis, adenomyosis and uterine fibroid-related dysmenorrhea."

Journal • Review • Endometriosis • Gynecology • Pain • Solid Tumor • Uterine Leiomyoma • Women's Health

ASTEROID 6: Assess Safety and Efficacy of Vilaprisan in Subjects With Uterine Fibroids (clinicaltrials.gov) - P3 | N=1272 | Terminated | Sponsor: Bayer | Active, not recruiting ➔ Terminated; Due to a change in the development program, the study was closed prematurely.

Trial termination • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health

Vilaprisan for the treatment of symptomatic endometriosis: results from a terminated phase 2b randomized controlled trial. (PubMed, F S Rep) - P2b | "Further studies in larger populations would be needed to accurately assess treatment effects. NCT03573336."

Clinical • Journal • P2b data • Endometriosis • Gynecology • Musculoskeletal Pain • Pain • Women's Health

Experimental and new investigational drugs for the treatment of uterine fibroids. (PubMed, Expert Opin Investig Drugs) - "Despite ulipristal acetate's well-established efficacy as a selective progesterone receptor modulator (SPRM) in fibroid treatment, its prescription has declined due to the rare but severe risk of liver damage. Oral GnRH antagonists, like elagolix, relugolix, and linzagolix, with their novel pharmacodynamic properties, are gaining traction in fibroid management, inducing a dose-dependent reduction in circulating sex hormone levels. Ongoing research on natural compounds, such as vitamin D and epigallocatechin gallate (EGCG), presents emerging options for treating uterine fibroids. This evolving landscape reflects the ongoing efforts to improve therapeutic outcomes for individuals with symptomatic uterine fibroids."

Journal • Review • Gynecology • Oncology • Solid Tumor • Uterine Leiomyoma • Women's Health

Efficacy and safety of vilaprisan in women with uterine fibroids: data from the ASTEROID 3 randomized controlled trial. (PubMed, F S Sci) - "Vilaprisan is efficacious and well tolerated over 12 weeks in the treatment of heavy menstrual bleeding associated with uterine fibroids. Further investigations of the long-term efficacy and safety of vilaprisan are warranted."

Clinical • Journal • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health

Research advances in drug therapy of endometriosis. (PubMed, Front Pharmacol) - "This paper investigated Genetic changes, estrogen-dependent inflammation induction, progesterone resistance, imbalance in proliferation and apoptosis, angiogenesis, lymphangiogenesis and neurogenesis, and tissue remodeling in its pathogenesis; and explored the pharmacological mechanisms, constitutive relationships, and application prospects of each compound in the text...In clinical trials, Quinagolide showed no statistical difference with the placebo group; the results of phase II clinical trial of the IL-33 antibody have not been announced yet; clinical trial stage III of vilaprisan was suspended due to drug toxicity...The results of a clinical study of Linzagolix in patients with moderate to severe endometriosis-related pain have not been disclosed yet. Letrozole improved the fertility of patients with mild endometriosis. For endometriosis patients with infertility, oral GnRH antagonists and aromatase inhibitors are promising drugs, especially Elagolix and Letrozole."

Journal • Review • Endometriosis • Gynecology • Infertility • Inflammation • Musculoskeletal Pain • Pain • Sexual Disorders • Women's Health • IL33

ASTEROID 5: Assess Safety and Efficacy of Vilaprisan in Subjects With Uterine Fibroids (clinicaltrials.gov) - P3 | N=766 | Terminated | Sponsor: Bayer | Completed ➔ Terminated; Due to a change in the development program, the study was closed prematurely.

Trial termination • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health

Assess Safety and Efficacy of Vilaprisan in Subjects With Uterine Fibroids (ASTEROID 3) (clinicaltrials.gov) - P3 | N=93 | Terminated | Sponsor: Bayer | Completed ➔ Terminated; Due to a change in the development program, the study was closed prematurely.

Trial termination • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health

Impact of Vilaprisan (VPR), on Cell Cycle & Cell Proliferation in Human Endometrium. (SRI 2023) - P3 | "Data support hypothesis that the antiproliferative effect of VPR is due to an impact on the cell cycle; at G1/M, G2/S & mitotic progress mediated through CDK4 & FOXM1."

Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health • ALPG • CDK4 • FOXM1 • Mucin 6 • NELL1

Comparing the pharmacokinetic and pharmacodynamic qualities of current and future therapies for uterine fibroids. (PubMed, Expert Opin Drug Metab Toxicol) - "To date, the most recent therapeutic strategies for uterine fibroids are represented by gonadotropin-releasing hormone antagonists (GnRH-ants; elagolix and relugolix) and selective progesterone receptor modulators (SPRM; ulipristal acetate). After early promising results, studies on innovative drugs, such as linzagolix (GnRH-ant) and vilaprisan (SPRM) are demanding. In the near future, a deeper knowledge of biological mechanisms at the basis of the genesis and growth of uterine fibroids could pave the way for the development of innovative targeted therapies."

Journal • PK/PD data • Gynecologic Cancers • Gynecology • Long-acting Reversible Contraceptives • Oncology • Solid Tumor • Uterine Leiomyoma • Women's Health • PGR

Sex Steroid Receptors in Polycystic Ovary Syndrome and Endometriosis: Insights from Laboratory Studies to Clinical Trials. (PubMed, Biomedicines) - "Understanding PCOS and the pathological roles of endometriosis sex steroid receptors is crucial for developing potential therapeutic strategies to treat infertility in both conditions. Therefore, research should be continued to fill the knowledge gap regarding the subject."

Journal • Review • Endometriosis • Gynecology • Infertility • Metabolic Disorders • Polycystic Ovary Syndrome • Sexual Disorders • Women's Health • AR • ER • PGR

ASTEROID 8: A Study to Assess the Safety and Efficacy of Vilaprisan in Japanese Subjects With Uterine Fibroids and Heavy Menstrual Bleeding (clinicaltrials.gov) - P3 | N=153 | Terminated | Sponsor: Bayer | Completed ➔ Terminated; Due to a change in the development program, the study was closed prematurely.

Trial termination • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health

Assess Safety and Efficacy of Vilaprisan in Subjects With Uterine Fibroids (ASTEROID 4) (clinicaltrials.gov) - P3 | N=103 | Terminated | Sponsor: Bayer | Completed ➔ Terminated; Due to a change in the development program, the study was closed prematurely.

Trial termination • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health

Assess Safety and Efficacy of Vilaprisan in Subjects With Uterine Fibroids (ASTEROID 3) (clinicaltrials.gov) - P3 | N=93 | Completed | Sponsor: Bayer | Active, not recruiting ➔ Completed

Trial completion • Gynecology • Solid Tumor • Uterine Leiomyoma

Systematic review of oral pharmacotherapeutic options for the management of uterine fibroids. (PubMed, J Am Pharm Assoc (2003)) - "Given higher quality of evidence, confirmed therapeutic efficacy, and a milder adverse effect profile, the contemporary gonadotropin releasing hormone antagonists (elagolix, relugolix, linzagolix) and vilaprisan represent preferred oral treatment options for the management of uterine fibroids."

Journal • Review • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health

Efficacy and safety of vilaprisan in the treatment of heavy menstrual bleeding due to uterine fibroids: Data from the ASTEROID 3 phase 3 clinical study (SEUD 2021) - No abstract available

Clinical • P3 data • Gynecology • Solid Tumor • Uterine Leiomyoma

ASTEROID 6: Assess Safety and Efficacy of Vilaprisan in Subjects With Uterine Fibroids (clinicaltrials.gov) - P3; N=1272; Active, not recruiting; Sponsor: Bayer; Trial completion date: Oct 2021 ➔ Jun 2024

Clinical • Trial completion date • Gynecology • Solid Tumor • Uterine Leiomyoma

ASTEROID 5: Assess Safety and Efficacy of Vilaprisan in Subjects With Uterine Fibroids (clinicaltrials.gov) - P3; N=766; Completed; Sponsor: Bayer; Active, not recruiting ➔ Completed

Clinical • Trial completion • Gynecology • Solid Tumor • Uterine Leiomyoma • MRI

Single- and Multiple-Dose Pharmacokinetics and Safety of Vilaprisan in Healthy Postmenopausal Japanese Women: A Randomized Clinical Trial. (PubMed, Eur J Drug Metab Pharmacokinet) - "Overall, vilaprisan was safe and well tolerated. The exposure in Japanese women was similar to that observed in European and Chinese women in separate studies."

Clinical • Journal • PK/PD data

Clinical Pharmacokinetics and Pharmacodynamics of the Selective Progesterone Receptor Modulator Vilaprisan: A Comprehensive Overview. (PubMed, Clin Pharmacokinet) - "Vilaprisan shows a steep exposure-response relationship for inducing amenorrhea in patients with uterine fibroids experiencing heavy menstrual bleeding. Based on simulations, a dose of 2 mg/day is expected to induce a maximum bleeding reduction and was thus selected for phase III."

Clinical • Journal • PK/PD data • Review • Endometriosis • Gynecology • Hepatology • Solid Tumor • Uterine Leiomyoma • Women's Health • CYP3A4

Assess Safety and Efficacy of Vilaprisan in Subjects With Uterine Fibroids (ASTEROID 4) (clinicaltrials.gov) - P3; N=103; Completed; Sponsor: Bayer; Active, not recruiting ➔ Completed

Trial completion • Gynecology • Solid Tumor • Uterine Leiomyoma

Assessment of the safe and efficacious dose of the selective progesterone receptor modulator vilaprisan for the treatment of patients with uterine fibroids by exposure-response modelling and simulation. (PubMed, Br J Clin Pharmacol) - "A 2 mg/day dose was selected for Phase 3 as E-R analyses show this dose results in a close to maximum probability for IA, without any safety concerns noted."

Clinical • Journal • Gynecology • Obesity • Solid Tumor • Uterine Leiomyoma • Women's Health

ASTEROID 8: A Study to Assess the Safety and Efficacy of Vilaprisan in Japanese Subjects With Uterine Fibroids and Heavy Menstrual Bleeding (clinicaltrials.gov) - P3; N=153; Completed; Sponsor: Bayer; Active, not recruiting ➔ Completed

Clinical • Trial completion • Gynecology • Solid Tumor • Uterine Leiomyoma

ASTEROID 8: A Study to Assess the Safety and Efficacy of Vilaprisan in Japanese Subjects With Uterine Fibroids and Heavy Menstrual Bleeding (clinicaltrials.gov) - P3; N=153; Active, not recruiting; Sponsor: Bayer; Trial completion date: May 2021 ➔ Aug 2021

Clinical • Trial completion date • Gynecology • Solid Tumor • Uterine Leiomyoma