vosilasarm (EP0062) / Radius, Ellipses Pharma - LARVOL DELTA

RAD-140 - Induced Hepatotoxicity: A Case of Severe Liver Injury From a Selective Androgen Receptor Modulator (ACG 2026) - "Figure: Table 1. Different laboratory parameters over the course of admission"

Clinical • CNS Disorders • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Hepatic Encephalopathy • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Liver Failure

Severe Cholestatic Drug-Induced Liver Injury Associated With SARM Stacking and Herbal Supplements (ACG 2026) - "He reported three years of Ashwagandha, Fadogia root, and Tongkat Ali herbal use, with recent stacking of RAD-140, LGD-4033, and MK-677...N-acetylcysteine and ursodiol were initiated...He was discharged on an oral prednisone taper...Lastly, transaminase fluctuations during recovery should be interpreted with adjunctive markers such as creatine phosphokinase, aldolase, and 5'-nucleotidase to avoid unnecessary steroid use. Figure: Figure 1: Visualization of the liver enzyme and total bilirubin trend during the treatment and recovery course with significant events noted."

Cholestasis • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Myositis • Pruritus

Unregulated gains: a case of RAD-140-induced liver injury. (PubMed, Proc (Bayl Univ Med Cent)) - "Despite drug cessation and corticosteroid therapy, he developed progressive hyperbilirubinemia requiring plasmapheresis, with a course complicated by pancreatitis and acute kidney injury requiring intensive care. This case represents the most severe manifestation of RAD-140-associated liver injury reported to date."

Journal • Acute Kidney Injury • Critical care • Hepatology • Liver Failure • Nephrology • Pancreatitis • Renal Disease

Exploiting androgen receptor agonism as a treatment strategy in estrogen receptor-positive metastatic breast cancer. (PubMed, NPJ Breast Cancer) - "A transcriptional signature associated with SARM sensitivity was identified, primarily driven by proliferation-related processes, consistent with a significant decrease in S-phase cell cycle proteins upon treatment in EP0062-sensitive models. In some EP0062-resistant tumors, the combination with palbociclib enhanced the antitumor effect of EP0062, suggesting a potential strategy for metastatic patients with acquired ET resistance."

Journal • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • AR • ER • GATA3 • PIK3CA • PTEN

A phase 1/2 study of EP0062 (vosilasarm), a first-in-class oral selective androgen receptor modulator (SARM), in combination with standard-of-care endocrine therapy +/- targeted therapies in patients with advanced or metastatic AR+/ER+/HER2− breast cancer. (ASCO 2026) - P1/2 | "EP0062 has been shown to inhibit the growth of AR+/ER+ BC PDX models as a single agent, and in combination with palbociclib, everolimus or elacestrant...Treatment arms are as follows: Arm 1: EP0062 + elacestrant (mandatory ESR1 mutation); Arm 2: EP0062 + exemestane + everolimus; Arm 3: EP0062 + fulvestrant + abemaciclib...Exploratory objectives are to evaluate potential biomarkers of efficacy, safety and/or PD activity. The study is currently recruiting across the three treatment arms in USA, UK, and Spain."

Clinical • Combination therapy • Metastases • P1/2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Spontaneous Splenic Rupture in a Patient With Recent Use of Performance-Enhancing Compounds: A Case Report and Literature Review. (PubMed, Cureus) - "We explore the potential and speculative role of performance-enhancing compounds in precipitating splenic complications, drawing parallels to the established association between traditional anabolic steroids and peliosis - blood-filled vascular cavities that predispose to rupture. While RAD-140 and MK-677 have not been previously linked to splenic pathology, their pharmacological effects on androgen receptor signalling and IGF-1 pathways warrant consideration as possible contributing factors, particularly in the context of a suspected pre-existing vascular malformation. Early recognition, aggressive resuscitation, and timely surgical intervention remain critical, as delayed diagnosis carries significant mortality."

Journal • Hematological Disorders • Pain • IGF1

Phase 1/2 Study to Evaluate EP0062 as Monotherapy and in Combination in Patients With Advanced or Metastatic AR+/HER-2-/ER+ Breast Cancer (clinicaltrials.gov) - P1/2 | N=95 | Recruiting | Sponsor: Ellipses Pharma | N=60 ➔ 95 | Trial completion date: Nov 2026 ➔ Feb 2028 | Trial primary completion date: Nov 2025 ➔ Feb 2028

Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • 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 • HER-2

Treatment with a selective androgen receptor modulator (RAD140) is linked to better cardiac function, with male-specific effects that are graded by interleukin-6. (PubMed, Geroscience) - "RAD140 treatment may enhance cardiac function in older male mice, but less so in older female mice. Increased circumferential strain in males related to lower interleukin-6 levels, supporting the AR's connecting role between cardiac function and inflammatory markers."

Journal • Cardiovascular • IL6

Initial testing procedure based on microextraction followed by LC-HRMS analysis to determine 107 xenobiotics and their metabolites in serum/plasma. (PubMed, Analyst) - "In contrast, at 22 °C several thiazide-based compounds were completely degraded after 4 weeks; FG2216 was no longer detectable after 7 weeks; S6 and RAD140 were no longer detectable after 9 weeks, whereas trenbolone was completely degraded after 14 weeks. The other compounds were still visible for the entire study period, with variations in the range of 37-56%."

Journal

Cholestatic Drug-Induced Liver Injury From Rad-140 Successfully Treated With Corticosteroids. (PubMed, ACG Case Rep J) - "Treatment is primarily supportive with drug cessation and cholestasis can take weeks to months to normalize. We present an atypical case of prolonged cholestasis caused by the readily available selective androgen receptor modulator called RAD-140 that was successfully managed with corticosteroids."

Journal • Cholestasis • Hepatology • Liver Failure

Preclinical assessment of the selective androgen receptor modulator RAD140 to increase muscle mass and bone mineral density. (PubMed, Physiol Rep) - "RAD140 did not impact cortical or trabecular bone structural morphometric properties following 14 days of treatment. The data presented here show the potential of RAD140 to stimulate muscle hypertrophy in young healthy rats."

Journal • Preclinical • Myositis

Exploring transdermal SARMs exposure: Analysis of the elimination profiles and metabolism for doping control purposes. (PubMed, J Anal Toxicol) - "The objective of this project was to simulate a transdermal contamination scenario and investigate the skin penetration and subsequent metabolism of microdoses of three commonly used SARMs: LGD-4033, RAD140, and S-23. It was demonstrated for all three SARMs that they penetrate the skin and may-even in trace amounts-produce AAFs when administered transdermally. Information on urinary concentrations and metabolism following transdermal administration of SARMs may assist in the interpretation of AAFs, particularly when dermal contamination or intentional doping via the skin is discussed."

Journal

Rapid detection of illegal selective androgen receptor modulators in unregistered supplements using a combination of selected solid-state analytical methods. (PubMed, ADMET DMPK) - "Unregistered dietary supplements containing anabolic substances, specifically selective androgen receptor modulators (SARMs) such as andarine, ligandrol, ostarine, and testolone became the subject of investigation. Overall, almost half of the analyzed samples of unregistered/illegal sports dietary supplements purchased anonymously online in the Slovak Republic with declared content of at least one SARM did not contain what is declared on the label. Thus the combination of several solid-state analytical techniques without complex sample preparation has proven valuable for rapid identification of APIs in supplements."

Journal

Results of a phase 1 study of vosilasarm (EP0062), a first-in-class oral selective androgen receptor modulator (SARM) in patients with advanced or metastatic AR+/ER+/HER-2- breast cancer. (ASCO 2025) - P1/2 | "Vosilasarm has promising clinical benefit, safety and tolerability in this heterogeneous, heavily pre-treated population. This confirms the potential of vosilasarm, a first in class SARM, as a new treatment strategy for AR+/ ER+/HER-2- breast cancer. The study is continuing with evaluation of vosilasarm in combination with SoC therapies including oral SERD, mTOR inhibitor and CDK4/6 inhibitors."

Clinical • Metastases • P1 data • Anemia • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • TP53

The impact of a selective androgen receptor modulator (RAD140) on frailty and underlying mechanisms in older male and female C57Bl/6 mice. (PubMed, Mech Ageing Dev) - "Six-weeks of RAD140 treatment did not affect frailty in older male or female mice. The beneficial effects in lean mass, bone mineral density, and systemic inflammation warrant longer treatments to explore any positive impact on frailty in males. RAD140 may not be ideal for achieving these in females."

Journal • Preclinical • Inflammation • AR • IL6

Deep Learning-Based Drug Compounds Discovery for Gynecomastia. (PubMed, Biomedicines) - "DTI analysis and DeepPurpose predictions identified 12 potential drugs, including conteltinib, yifenidone and vosilasarm, with high predicted binding affinities to the target genes. The findings highlight the effectiveness of combining text mining and artificial intelligence in drug discovery. This innovative method provides a new avenue for developing specific treatments for gynecomastia and underscores the need for further experimental validation and optimization of prediction models to support novel drug development."

Journal • IGF1 • TGFB1

Phase 1/2 Study to Evaluate Vosilasarm (EP0062) as Monotherapy and in Combination in Patients With Advanced or Metastatic AR+/HER-2-/ER+ Breast Cancer (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: Ellipses Pharma | N=128 ➔ 60 | Trial completion date: Mar 2025 ➔ Nov 2026 | Trial primary completion date: Dec 2024 ➔ Nov 2025

Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • 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 • HER-2

A study to evaluate the safety and efficacy of vosilasarm (EP0062), an oral SARM, as monotherapy and in combination with standard of care regimens in patients with relapsed locally advanced or metastatic AR+/HER2-/ER+ breast cancer (SABCS 2024) - P1/2 | "Vosilasarm + elacestrant in patients with AR+/HER2-/ER+/ESR1mut + advanced/metastatic breast cancer that has progressed on one or two prior lines of endocrine therapy, including prior CDK4/6 inhibitor Cohort 2. Vosilasarm + everolimus + exemestane in patients with AR+/HER2-/ER+ advanced/metastatic breast cancer that has progressed on a prior endocrine therapy + CDK4/6 inhibitor Key inclusion criteria are as follows: Post-menopausal women, ≥18 years ECOG performance status of 0 to 1 Locally advanced or metastatic breast cancer ER+, HER2- as per ASCO CAP guidelines AR+, as defined as ≥ 10% AR nuclei staining by IHC Endocrine-therapy-sensitive breast cancer defined as: a) greater than 2 years of adjuvant endocrine therapy prior to development of advanced or metastatic disease, OR b) previous response (without disease progression for at least 6 months) to one of the following treatments in the advanced/metastatic setting: SERD +/- CDK 4/6 inhibitor, AI +/- CDK 4/6..."

Clinical • Combination therapy • Metastases • Monotherapy • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • AR • ER • HER-2

Severe Drug-Induced Liver Injury Due to RAD-140 Use (ACG 2024) - "The case illustrates that healthcare providers should be aware that nonmedical supplement use like RAD-140 can cause severe hepatotoxicity, and developing acute liver failure necessitating liver transplantation is always a possibility. Patients usually require close outpatient monitoring as the recovery period can be prolonged, and it may take 3-5 months for liver biochemistries to normalize."

CNS Disorders • Cytomegalovirus Infection • Dermatology • Epstein-Barr Virus Infections • Hematological Disorders • Hepatology • Infectious Disease • Inflammation • Liver Failure • Pruritus

Severe Drug-Induced Liver Injury Due to Testolone, A Selective Androgen Receptor Modulator (ACG 2024) - "Empiric N-acetylcysteine, cholestyramine, and ursodiol were started. Figure: Figure 1A: Liver biopsy showing marked canalicular cholestasis consistent with DILI. Figure 1B: Budesonide treatment started on day 9 demonstrating a steady downtrend in total bilirubin."

Alzheimer's Disease • Cholestasis • CNS Disorders • Hepatology • Inflammation • Liver Failure • Muscular Dystrophy • Osteoporosis • Pruritus • Rheumatology

Identification of biomarkers of response and the mechanism of action of a selective androgen receptor modulator in estrogen receptor-positive breast cancer patient-derived xenografts (EORTC-NCI-AACR 2024) - "Adding the CDK4/6 inhibitor palbociclib enhanced the antitumor activity of EP0062 or fulvestrant in ESR1-mutant models but not in HER2-enriched or PTEN-mutant PDX models...EP0062 triggers an E2F1 downmodulation which mediates a potent antiproliferative activity. For EP0062-resistant tumors that remain ER-driven, the addition of palbociclib displays a potent antitumor effect."

Biomarker • Clinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AR • E2F1 • ER • FOXA1 • GATA3 • HDAC2 • HER-2 • PIK3CA • PTEN

Selective Androgen Receptor Modulators Leading to Liver Injury: A Case Report. (PubMed, Cureus) - "Discontinuation of RAD-140 appears to reverse liver injury, but the long-term effects and risks of SARM use remain unclear. This case highlights the need for caution and monitoring when considering SARMs for performance enhancement."

Journal • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Liver Failure

Myopericarditis Following Use of Selective Androgen Receptor Modifier "RAD-140". (PubMed, JACC Case Rep) - "We report the case of a 16-year-old boy who had myopericarditis following the first dose of a selective androgen receptor modulator called Testolone ("RAD-140"). These drugs are widely abused by physically active young adults; however, the drugs' side effects, which can be life-threatening, are not well characterized."

Journal • Cardiovascular • Inflammation • AR

Reversible Gynecomastia and Hypogonadism Due to Usage of Commercial Performance-Enhancing Supplement Use. (PubMed, JCEM Case Rep) - "These performance-enhancing supplements were found to contain amounts of RAD-140, a selective androgen receptor modulator, MK-677, a GH secretagogue and cardarine, all of which are banned PEDs. Cessation of these supplements led to full resolution of symptoms including normalization of hypogonadotropic hypogonadism. This case highlights the need for clinicians to consider commercially available performance-enhancing supplements as potential sources of PEDs and exogenous steroid hormones that can have adverse clinical consequences."

Journal • Endocrine Disorders

Detection of nonsteroidal and steroidal selective androgen receptor modulators in equine hair after oral administrations. (PubMed, Drug Test Anal) - "To better control the misuse of RAD140 and YK-11 in horses, two separate oral administration studies of RAD140 (0.3 mg/kg daily for 3 days) and YK-11 (0.2 mg/kg daily for 3 days) were previously conducted to investigate their metabolism and to identify target analyte(s) with the longest detection time in urine and plasma for doping control. In this work, segmental analyses of post-administration hair samples have revealed that (i) RAD140 and YK-11 could be detected in horse mane after oral administration and (ii) internal incorporation of RAD140 into hair via bloodstream and external incorporation through sweat or sebum were both observed, whereas YK-11 was primarily incorporated into hair via sweat or sebum."

Journal