Ostarine (enobosarm) / Veru Inc - LARVOL DELTA

Muscle Loss in Obesity Therapy as a Therapeutic Target: Trial Design and Endpoints for Regulatory Discussions. (PubMed, J Cachexia Sarcopenia Muscle) - "Discussions highlighted the impact of glucagon-like peptide-1 (GLP-1) receptor agonists or GLP-1/glucose-dependent insulinotropic polypeptide (i.e., GLP-1/GIP) agonists on body composition and muscle health; the challenges of distinguishing 'true' skeletal muscle from fat-free tissue; the impact of treatment discontinuation and weight regain; advances in imaging and quantitative assessment of lean body mass; as well as insights from emerging muscle-preserving therapies (e.g., bimagrumab, pemvidutide and enobosarm)...These also involve significant regulatory considerations for future drug development and approval pathways, for instance related to the very large number of individuals that may be considered for these therapeutic approaches as well as from the potential long (or life-long) duration of therapy considered with these drugs. Together, these discussions highlight the growing importance of integrating body composition and functional assessments in future..."

Journal • Cachexia • Genetic Disorders • Obesity • Sarcopenia

Sarcopenia in Aging: Pathogenesis, Diagnosis, and Emerging Therapeutic Frontiers. (PubMed, Mol Imaging Biol) - "Resistance-based exercise and targeted nutritional support remain first-line, but late-phase trials of myostatin-neutralising antibodies (e.g., LY2495655, bimagrumab) and oral selective androgen-receptor modulators (SARMs; e.g., enobosarm, GSK2881078) now show dose-dependent gains in appendicular lean mass and preliminary functional benefits, signalling that combination regimens integrating lifestyle and drug therapy are imminent. Addressing these challenges requires an interdisciplinary strategy that encompasses molecular, clinical, and public health perspectives to mitigate the personal and societal impacts of sarcopenia. Future efforts must focus on harmonizing diagnostic criteria, refining therapeutic regimens, and leveraging emerging technologies to develop targeted interventions that preserve muscle function and enhance quality of life in the aging population."

Journal • Review • Inflammation • Metabolic Disorders • Muscular Atrophy • Sarcopenia

Nutrition in cachexia: support by pharmacological options? (DGHO 2025) - "According to initial clinical studies there is a group of particularly promising agents, including: the selective androgen enobosarm, S-pindolol, which has a mixed effect on beta receptors, the central appetite stimulant anamorelin, which has been approved in Japan, the cytokine-blocking substances bermekimab (anti-IL1alpha), tocilizumab (anti-IL6) and ruxolitinib (Jak1/2 inhibitor), the atypical neuroleptic olanzapine and newer GDF-15 antibodies such as ponsegromab. For approval, effects on the spectrum of symptoms, performance and body composition will probably be required."

Anorexia • Cachexia • Fatigue • GDF15 • IL1A

Enobosarm in Combination With GLP-1RA is Selective for Fat Loss While Preserving Lean and Function (OBESITY WEEK 2025) - "Phase 2b QUALITY clinical trial is the first human study to show that older patients who are overweight or have obesity and receiving a GLP-1 RA, are at higher risk for accelerated loss of lean mass and associated physical function decline. Oral enobosarm improves body composition by driving a more selective and greater loss of adiposity (fat mass) and preserving both lean mass and physical function in patients receiving semaglutide for chronic weight management."

Combination therapy • Genetic Disorders • Obesity

Enobosarm Reduced Body Weight and Fat Regain and Preserved Lean Mass After Discontinuing Semaglutide (OBESITY WEEK 2025) - "The Phase 2b QUALITY and Maintenance Extension clinical trial confirms that preserving lean mass with enobosarm plus semaglutide led to greater fat loss during the active weight loss period, and after semaglutide was discontinued, enobosarm monotherapy significantly prevented the regain of both weight and fat mass during the maintenance period such that by end of study there was greater loss of fat mass while preserving lean mass for a higher quality weight reduction compared to the placebo group."

Genetic Disorders • Obesity

Pharmacological intervention: Challenges and promising outcomes for fat loss and preservation of lean body mass in the treatment of overweight and type 2 diabetes. (PubMed, Diabetes Obes Metab) - "Activin II receptor inhibition with bimagrumab demonstrated significant preservation and increases in LBM, along with FM reduction, in both preclinical and phase 2 studies in individuals with overweight and T2D. Similar effects were observed for myostatin and activin A inhibitors (trevogrumab, garetosmab), latent myostatin inhibitors (apitegromab, SRK-439), and Selective Androgen Receptor Modulators (enobosarm)...Pharmacological adjunct therapies show potential for improving body composition and physical function during GLP-1 RA-induced weight loss. Preliminary findings are promising, but larger, controlled trials are necessary to confirm efficacy and safety before clinical implementation can be considered."

Journal • Review • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Veru Announces Pricing of $25 Million Public Offering (GlobeNewswire) - "Veru intends to use the net proceeds from the proposed offering to fund the development of enobosarm, with a primary focus on Phase 2b PLATEAU clinical study activities. Some of the proceeds will also be used for working capital purposes, including existing vendor obligations, and for other general corporate purposes including working with potential development partners for enobosarm."

Commercial • New P2b trial • Obesity

Effects of Combined Treatment With Selective Androgen and Estrogen Receptor Modulators Ostarine and Raloxifen on Bone Tissue In Ovariectomized Rats. (PubMed, Calcif Tissue Int) - "Here, a combined treatment with a selective estrogen receptor modulator (raloxifene, RAL) and a selective androgen receptor modulator (ostarine, OST) was investigated in ovariectomized rats. Conversely, the combined treatment increased serum phosphorus and luteinizing hormone levels, decreased serum magnesium and calcium, and did not attenuate the organ and uterus weight increase observed after OST, raising safety concerns. These findings highlight the need for cautious evaluation of combination therapies and suggest that there is a need for alternative compounds with improved safety profiles for future osteoporosis treatments."

Journal • Preclinical • Osteoporosis • Rheumatology

The FDA now accepts incremental weight loss as a primary endpoint for approval when enobosarm is added to GLP-1 receptor agonist treatment. The agency also confirmed that the 3mg dosage of enobosarm is acceptable for future clinical development and encouraged Veru to include younger patients with obesity in its studies. (Investing.com) - "Veru plans to initiate a Phase 2b clinical trial called PLATEAU in the first quarter of 2026, pending sufficient capital. The study will evaluate enobosarm 3mg in approximately 180 older and younger patients with obesity who are starting tirzepatide treatment for weight reduction."

FDA event • New P2b trial • 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=168 | Completed | Sponsor: Veru Inc. | Active, not recruiting ➔ Completed | Trial completion date: Apr 2025 ➔ Aug 2025 | Trial primary completion date: Dec 2024 ➔ Apr 2025

Trial completion • Trial completion date • Trial primary completion date • Genetic Disorders • Obesity

Current Status and Advances in Anti-Androgen Therapy for Triple-Negative Breast Cancer. (PubMed, Curr Med Sci) - "The treatment of AR-positive TNBC relies primarily on androgen receptor antagonists, such as enobosarm, bicalutamide, and enzalutamide. However, anti-AR therapies face significant limitations and challenges due to multifaceted factors, necessitating further resolution. With continued advancements, AR-targeted therapy holds promise as a critical component of personalized treatment strategies for TNBC."

Journal • Review • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Veru Announces Selection of Novel Modified Release Oral Enobosarm Formulation for Chronic Weight Loss Management Following Pharmacokinetic Clinical Study (GlobeNewswire) - "The single dose, open label pilot study evaluated the plasma concentration versus time profile of a proprietary, patentable modified release formulation of enobosarm 3mg. The new formulation demonstrated the intended distinct target product release profile, which includes a reduction in maximum plasma concentration (Cmax), a delayed time to maximum plasma concentration (Tmax), a distinct secondary peak plasma concentration, and similar extent of absorption (AUC) compared to historical values for enobosarm immediate release capsules."

Clinical data • PK/PD data • Obesity

Laxxon Medical Announces Successful Product Development Milestone with Novel Oral Modified-Release Formulation of Veru’s Enobosarm, Utilizing Laxxon’s SPID-Technology (Businesswire) - "Laxxon Medical...announced that Veru Inc...has selected a novel modified-release oral formulation of enobosarm that will utilize Laxxon’s proprietary SPID (Screen Printing Innovation Drug)-Technology."

Commercial • Obesity

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