Ostarine (enobosarm) / Veru Inc - LARVOL DELTA

The Potential of SARMs and Antimyostatin Agents in Addressing Lean Body Mass Loss From GLP-1 Agonists: A Literature Review. (PubMed, J Diabetes) - "Several of these agents, such as enobosarm, have been investigated in clinical trials involving older patient populations or patients with cachexia or sarcopenia secondary to chronic diseases...This review aims to evaluate the potential benefits and uses of SARMs in ameliorating the body composition changes induced by GLP-1 RAs. Other investigational agents to retain or increase muscle mass and the future possibilities of these drugs will be discussed."

Journal • Review • Cachexia • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Sarcopenia

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

Selective androgen receptor modulators (SARMs) - potential anabolic drugs for the treatment of cachexia and frailty syndrome. (PubMed, Endokrynol Pol) - "Two compounds, GTx-024/MK-2866 (enobosarm) and GSK2881078, are currently being tested in clinical trials. This paper discusses their effects and potential use in future cachexia and frailty therapies."

Journal • Review • Anorexia • Cachexia • Geriatric Disorders • Sarcopenia

Androgen Receptor Loss Drives Nuclear Instability in Cancer-Associated Fibroblasts: A Novel Mechanism of Tumor-Stroma Remodeling (EACR 2025) - "Genetic AR overexpression and pharmacological activation with the synthetic AR agonist ostarine were used to rescue nuclear abnormalities... This study uncovers a previously unrecognized AR-lamin axis that safeguards nuclear integrity in the tumor microenvironment. The accumulation of phosphorylated lamin A/C and nuclear abnormalities in SCC and melanoma stroma suggests that AR loss drives CAF activation through lamin-mediated chromatin remodeling. By weakening stromal resilience and promoting tumor-supportive CAFs, AR depletion fuels tumor progression."

Stroma • Melanoma • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • AR • CAFs • LMNA

Veru Reports Positive Results from Phase 2b QUALITY and Maintenance Extension Study Showing Enobosarm Significantly Reduced Body Weight Regain, Prevented Fat Regain, and Preserved Lean Mass After Semaglutide Discontinuation (GlobeNewswire) - P2 | N=150 | QUALITY (NCT06282458) | Sponsor: Veru Inc. | "During the Maintenance Period of 12 weeks after discontinuing semaglutide (GLP-1 receptor agonist), placebo group regained 43% of body weight that was previously lost during Phase 2b QUALITY study; on average, enobosarm 3mg significantly reduced body weight regain by 46% and completely prevented fat regain compared to placebo.The enobosarm treated groups showed up to 93% greater fat loss and 100% lean mass preservation compared to the placebo group at the end of the study. Enobosarm monotherapy had a positive safety profile with essentially no gastrointestinal side effects during the maintenance treatment period. Based on efficacy and safety from Phase 2b QUALITY and Maintenance Extension study: (i) Enobosarm 3mg will advance as the proposed oral dose for the Phase 3 clinical program; (ii) Veru has been granted a meeting with FDA to discuss the Phase 3 clinical program."

FDA event • P2b data • Obesity

SARMs, Metabolic Modulators and Growth Hormone Secretagogues in Suspected Illegal Medicines, Bought as Sport Performance Enhancers: A Retro- and Prospective Study Within the GEON. (PubMed, Drug Test Anal) - "Eighteen different molecules, within the scope of the study, were reported with as top 5: ibutamoren, ligandrol, ostarine, cardarine and andarine. From the limited quantitative data reported, it can be assumed that the majority of the samples contain active doses and some are even overdosed, so health risks for the consumers cannot be neglected."

Journal

A single dose of 20-mg of ostarine is detectable in hair. (PubMed, Clin Chem Lab Med) - No abstract available

Journal

A Computational and In Vitro Appraisal of Ostarine to Target Androgen Receptor in Glioma C6 Cells. (PubMed, Cell Biochem Biophys) - "The IC50 value of Ostarine demonstrated a twofold-increase in the inhibition of C6 cells as compared to Bicalutamide. Further, cell viability, cell migration and cell invasion assays indicated the potential of Ostarine as an AR antagonist that holds chemotherapeutic promise in containing the propagation of gliomas C6 cells."

Journal • Preclinical • Brain Cancer • Glioma • Oncology • Solid Tumor

Sarcopenia in Ageing and Chronic Illness: Trial Endpoints and Regulatory Issues. (PubMed, J Cachexia Sarcopenia Muscle) - "Furthermore, novel therapeutic approaches were explored, including 20-hydroxyecdysone, enobosarm, anamorelin, ponsegromab, and nutritional supplementation, alongside broader strategies targeting myostatin-activin signalling inhibition and Akt pathway activation. Given that the population that may be addressed in aging associated sarcopenia is vast, the safety requirement standards applied for studies may be equivalent to those of studies in type 2 diabetes mellitus. Some argued at the meeting that this would make study programs so large that from an economic standpoint only therapies that significantly impact on morbidity/mortality outcomes have a chance to be considered commercially feasible for development."

Journal • Cachexia • Diabetes • Metabolic Disorders • Sarcopenia • Type 2 Diabetes Mellitus

Veru Reports Positive Safety Results from Phase 2b QUALITY Study: Enobosarm Added to Semaglutide Led to Greater Fat Loss, Preservation of Muscle, and Fewer Gastrointestinal Side Effects Compared to Semaglutide Alone (GlobeNewswire) - P2 | N=150 | QUALITY (NCT06282458) | Sponsor: Veru Inc. | "The topline efficacy and safety data for the Phase 2b extension maintenance study to assess whether enobosarm monotherapy prevents the fat and weight regain following discontinuation of semaglutide are expected in the second quarter...There were no increases in gastrointestinal side effects, no evidence of drug-induced liver injury (as defined by Hy’s law), and no increases in obstructive sleep apnea at any dose of enobosarm compared to placebo (semaglutide alone). There were no AEs of increases in prostate specific antigen in men....In the topline efficacy analysis, the trial met its prespecified primary endpoint with a statistically significant and a clinically meaningful benefit in all patients receiving enobosarm + semaglutide versus placebo + semaglutide at 16 weeks in total lean mass (71% relative reduction in lean mass loss, p=0.002)."

P2b data • Metabolic Disorders • Obesity

Novel Modified Release Oral Enobosarm Formulation is on Track to be Available for Phase 3 Clinical Studies and Commercialization (GlobeNewswire) - "Veru is currently developing a novel, patentable, modified release oral formulation for enobosarm. The actual formulation, pharmacokinetic release profile(s), and method of manufacturing will be the subjects of future patent applications. If issued, the expiry for the new modified release oral enobosarm formulation patent is expected to be 2045. The new enobosarm formulation has completed animal trials and is anticipated to be in Phase 1 bioavailability clinical trials during the first half of calendar 2025. The expectation is that this novel modified release oral enobosarm formulation will be available for the Phase 3 clinical studies and for commercialization."

New P1 trial • Patent expiry • Metabolic Disorders

Veru Reports Fiscal 2025 Second Quarter Financial Results and Clinical Program Progress (GlobeNewswire) - "Unblinded safety data from Phase 2b QUALITY study expected in the second quarter of calendar 2025...The topline efficacy and safety results for the Phase 2b extension clinical study are expected this quarter...As the Phase 2b QUALITY clinical trial is a positive study, we plan to request an End of Phase 2 meeting with the FDA. During the preIND FDA meeting, FDA provided general comments about a regulatory path forward for enobosarm as a drug that improves body composition during weight loss including input on Phase 3 clinical program design...The proposed Phase 3 clinical trial design is a double-blind, placebo-controlled study in older patients, greater than or equal to 60 years of age, who have obesity or who are overweight and who are eligible for treatment with GLP-1 RA....The new enobosarm formulation has completed animal trials and is anticipated to be in Phase 1 bioavailability clinical trials during the first half of calendar 2025."

New P1 trial • New P3 trial • P2b data • Obesity

Veru to Present at the 2nd Annual GLP-1-Based Therapeutics Summit (GlobeNewswire) - "Veru Inc...announced that the Company will present at the 2nd Annual GLP-1-Based Therapeutics Summit, taking place April 29 - May 1, 2025, in Boston, Massachusetts."

P2b data • Obesity

Veru Reports Fiscal 2025 First Quarter Financial Results and Clinical Program Progress (GlobeNewswire) - "The topline results of the separate blinded Phase 2b extension clinical study are expected in the second quarter of calendar 2025... Veru is currently developing a novel, patentable, modified release formulation for enobosarm...The drug product formulation is currently in animal trials and is anticipated to be available for a Phase 1 bioavailability clinical trial during the first half of calendar 2025...Veru had a pre-IND meeting with the FDA Division of Cardiology and Nephrology Center for Drug Evaluation and Research on December 26, 2024...The indication for discussion was the use of sabizabulin to slow progression or promote regression of atherosclerotic disease in patients with a history of coronary artery disease...The chronic nonclinical toxicology studies are expected to be completed and a new IND for the proposed indication is planned to be submitted by the first half calendar 2026."

IND • New P1 trial • P2b data • Atherosclerosis • Cardiovascular • Obesity

Next regulatory steps (GlobeNewswire) - "As the Phase 2b QUALITY study has positive topline clinical results, we are planning to move forward to request an end of Phase 2 meeting with FDA...We have previously met with FDA to discuss our regulatory path forward as an improvement in body composition drug, and FDA has provided general advice on Phase 3 design...Based on the Phase 2b QUALITY clinical trial, the proposed Phase 3 clinical trial design is currently expected to be a double-blind, placebo-controlled study in older (> 60 years of age), patients who have obesity or who are overweight and who are eligible for treatment with GLP-1 RA. The GLP-1 RA may be either WEGOVY (semaglutide) and/or Zepbound (tirzepatide)."

Clinical protocol • FDA event • Metabolic Disorders • Obesity

Veru Announces Positive Topline Data from Phase 2b QUALITY Clinical Study: Enobosarm Preserved Lean Mass in Patients Receiving WEGOVY (Semaglutide) for Weight Reduction (GlobeNewswire) - P2b | N=150 | QUALITY (NCT06282458) | Sponsor: Veru Inc. | "Study met primary endpoint: Enobosarm treatment resulted in statistically significant reduction in the loss of lean mass in subjects receiving WEGOVY (p=0.002); Patients on Enobosarm on average lost 71% less lean mass than patients receiving WEGOVY alone; Patients on Enobosarm on average lost 27% more fat mass than patients receiving WEGOVY alone; Enobosarm improved body composition as mean total body weight loss was similar compared to subjects receiving WEGOVY alone; Enobosarm reduced the proportion of patients that lost clinically significant physical function versus subjects receiving WEGOVY alone...The topline results for the separate blinded Phase 2b extension clinical study are expected in April of 2025."

P2b data • Metabolic Disorders • Obesity

Meta-analysis of Subjects from 4 RCTs Supports Potential of Enobosarm to Optimize Weight Loss (OBESITY WEEK 2024) - "In this meta-analysis of older obese subgroup, enobosarm reduced fat mass while preserving lean mass with weight loss of mostly fat. This supports the potential for enobosarm when combined with a GLP-1 RA to also preserve muscle, while preferentially reducing fat resulting in a higher quality weight loss obese patients. A Phase 2b randomized controlled trial is currently underway to evaluate the safety and efficacy of enobosarm in older patients receiving a GLP-1 RA for weight loss."

Retrospective data • Gastrointestinal Disorder • Lung Cancer • Obesity • Oncology • Solid Tumor

Selective Androgen Receptor Modulators (SARMs) Effects on Physical Performance: A Systematic Review of Randomized Control Trials. (PubMed, Clin Endocrinol (Oxf)) - "SARMs have a positive effect on physical performance and body composition and are associated with moderate rates of mild to moderate adverse effects (AEs) and a low rate of severe AEs."

Journal • Review • Cachexia • Oncology • Sarcopenia

Dose-Finding Study Evaluating Effect on Body Composition of Enobosarm in Patients Taking a GLP-1 for Chronic Weight Mgmt (clinicaltrials.gov) - P2 | N=150 | Active, not recruiting | Sponsor: Veru Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

In Vitro and In Vivo Human Metabolism of Ostarine, a Selective Androgen Receptor Modulator and Doping Agent. (PubMed, Int J Mol Sci) - "The production of cyanophenol-sulfate might participate in the mechanism of ostarine liver toxicity. We suggest ostarine-glucuronide (C25H22O9N3F3, diagnostic fragments at m/z 118, 185, and 269) and hydroxybenzonitrile-ostarine-glucuronide (C25H22O10N3F3, diagnostic fragments at m/z 134, 185, and 269) in non-hydrolyzed urine and ostarine and hydroxybenzonitrile-ostarine (C19H14O4N3F3, diagnostic fragments at m/z 134, 185, and 269) in hydrolyzed urine as markers to document ostarine intake in doping."

Journal • Preclinical • Hepatology

The disordering effect of SARMs on a biomembrane model. (PubMed, Phys Chem Chem Phys) - "Here, we report significant information related to the changes that ostarine, ligandrol, andarine, and cardarine produce in the thermodynamic properties of a lipid biomembrane model. By employing theoretical calculations, we gained insights into the possible electrostatic interactions between SARMs and phospholipid molecules, enhancing our understanding of the driving forces behind the interactions of SARMs with lipid membranes. Overall, this investigation provides relevant knowledge related to the biophysical-chemical effects that SARMs produce in biomembrane models and could be of practical reference for promising applications of SARMs in medicine and sport."

Journal

Atossa Therapeutics Announces Updated Protocol for Clinical Trial Evaluating (Z)-Endoxifen in Combination with Abemaciclib (VERZENIO) in Women with ER+/HER2- Breast Cancer (GlobeNewswire) - "Atossa Therapeutics, Inc...today announced protocol changes in the previously initiated study to evaluate Atossa’s proprietary (Z)-endoxifen in combination with abemaciclib (VERZENIO)...The study is investigating the combination as a neoadjuvant treatment in women with newly diagnosed Estrogen Receptor positive (ER+) / Human Epidermal Growth Factor Receptor 2 negative (HER2-) breast cancer...Based on accumulating data from the ongoing Phase 2 EVANGELINE study, the dose of (Z)-endoxifen in the combination study has been increased from 40 mg to 80 mg once daily. The change in study dose was determined following a review of safety, efficacy and pharmacokinetic (PK) data from participants currently enrolled in the 80 mg PK run-in cohort of the EVANGELINE study."

Clinical protocol • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor

Pooled Safety Analysis of Enobosarm from Phase 2 and Phase 3 Placebo-Controlled Clinical Trials (ADA 2024) - "In pooled analysis of 1027 older men, postmenopausal women, and older patients with muscle loss from advanced cancer, enobosarm was well tolerated with an AE profile comparable to the control patients. A Ph2b randomized trial is underway to evaluate enobosarm in older patients on a GLP-1 RA for weight loss."

Clinical • Late-breaking abstract • P2 data • P3 data • Metabolic Disorders • Obesity

Potential to Optimize Weight Loss with Enobosarm—Meta-analysis of Body Composition from Three Randomized Clinical Trials Support the Ability of Enobosarm to Preserve Muscle while Reducing Fat (ADA 2024) - "In meta-analysis of 367 older men, postmenopausal women, and older patients with muscle loss from advanced cancer, enobosarm therapy resulted in reductions in fat mass while preserving lean mass. Meta-analysis supports the potential for enobosarm when combined with a GLP-1 RA may preserve muscle, while preferentially reducing fat resulting in a higher quality weight loss in overweight and obese patients. A Phase 2b randomized controlled trial is currently underway to evaluate enobosarm in older patients receiving a GLP-1 RA for weight loss."

Late-breaking abstract • Retrospective data • Metabolic Disorders • Obesity

Dose-Finding Study Evaluating Effect on Body Composition of Enobosarm in Patients Taking a GLP-1 for Chronic Weight Mgmt (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Veru Inc. | N=90 ➔ 150

Enrollment change • Genetic Disorders • Obesity