Ostarine (enobosarm) / Veru Inc - LARVOL DELTA

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."

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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

Double-Blind, Multiple Ascending Dose, Safety, Pharmacokinetic and Body Composition Study of Enobosarm in Healthy Young and Older Men (AACE 2024) - "While enobosarm was associated with positive body composition changes in men regardless of age, older men with lower lean mass and higher fat mass at baseline appear more likely to have greater benefit from enobosarm therapy. An ongoing randomized controlled Phase 2b trial is enrolling to evaluate the safety and efficacy of enobosarm as a treatment to augment fat loss and to prevent muscle loss in sarcopenic obese or overweight elderly patients receiving a GLP-1 RA who are at-risk for developing muscle atrophy and muscle weakness."

Clinical • PK/PD data • Muscular Atrophy • Obesity

Potential to Optimize Weight Loss with Enobosarm: Augment Reduction of Fat Mass while Preserving Muscle in Older Patients with Obesity (AACE 2024) - "Discussion/Conclusion In a subset analysis of older obese patients, enobosarm therapy resulted in reductions in fat mass while preserving lean body mass (muscle) leading to greater high quality weight loss. A Phase 2b randomized controlled trial is currently underway to evaluate the safety and efficacy of enobosarm in preserving muscle mass and augmenting fat loss in at risk sarcopenic obese or overweight older patients receiving a GLP-1 RA for weight loss."

Clinical • Anorexia • Gastrointestinal Disorder • Genetic Disorders • Lung Cancer • Muscular Atrophy • Obesity • Oncology • Solid Tumor

Evidence of ostarine cross-contamination via sweat in 2 athletes sharing the same neoprene hamstring sleeves. An original situation of drug transfer where the anti-doping rule violation was suspended by the sport authorities. (PubMed, Clin Chim Acta) - "Ostarine was identified in 12 different selected pieces (about 1 g) of the sleeves at concentrations ranging from 3 to 142 pg/g. Sport authorities (USADA) agreed that the most likely source of contamination was the hamstring sleeves, thus confirming the scenario of drug transfer and gave the athlete a no fault."

Clinical • Journal • Observational data • Retrospective data • Review

Dose-Finding Study Evaluating Effect on Body Composition of Enobosarm in Patients Taking a GLP-1 for Chronic Weight Mgmt (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Veru Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

A screening method for the quantitative determination of selective androgen receptor modulators (SARMs) in capsules by high resolution 19F- and 1H-NMR spectroscopy. (PubMed, Anal Methods) - "A new method for rapid determination of the content of selective androgenic receptor modulators (SARMs) andarine, cardarine, ligandrol, ostarine and S-23 in capsules by 1H- and 19F-high resolution nuclear magnetic resonance spectroscopy was described and validated. The statistical analysis of the results from 19F- and 1H-quantitative NMR showed that both approaches were equally effective, thus expanding the potential use of the methodology to non-fluorinated SARMs. At present, no SARM has been approved for human consumption; however, SARMs are actually used by bodybuilders and recreational athletes, who purchase them even though the risk-benefit ratio of these molecules has not been definitively established."

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Evidence of ostarine excretion in oral fluid after a single controlled oral administration. (PubMed, Clin Chim Acta) - "Ostarine was detectable during the whole period of test, with concentrations at 1-2 ng/mL after T + 4 h. These results support drug transfer during kissing and subsequent possible contamination of the partner."

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Phase II Study of GTx024 in Women With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=22 | Terminated | Sponsor: GTx | Completed ➔ Terminated

Metastases • Trial termination • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AR • ER

Body fluid contamination in the context of an adverse analytical finding in doping: About a case involving ostarine. (PubMed, Clin Chim Acta) - "The dose ingested by the athlete was estimated at 15 µg. These results demonstrate the transfer of ostarine via body fluids between two subjects, with a high risk of AAF in one athlete, as observed in our case."

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