GSK2881078 / GSK - LARVOL DELTA

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

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

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

Qualitative interviews of patients with COPD and muscle weakness enrolled in a clinical trial evaluating a new anabolic treatment: patient perspectives of disease experience, trial participation and outcome assessments. (PubMed, J Patient Rep Outcomes) - P2a | "The qualitative interviews generated in-depth evidence of key concepts relevant to patients with COPD and muscle weakness and support the assessments of patient strength and physical function as outcome measures in this population in future studies."

Interview • Journal • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Systematic Review of Safety of Selective Androgen Receptor Modulators in Healthy Adults: Implications for Recreational Users. (PubMed, J Xenobiot) - "Two individuals exposed to GSK2881078 in a clinical trial were reported to have rhabdomyolysis. Recreational SARM use should be strongly discouraged, and the risks of DILI, rhabdomyolysis, and tendon rupture should be emphasized. However, despite warnings, if a patient refuses to discontinue SARM use, ALT monitoring or dose reduction may improve early detection and prevention of DILI."

Journal • Review • Hepatology • Liver Failure

In-depth metabolic study of non-steroidal selective androgen receptor modulator - GSK2881078 in thoroughbred horses and horse liver microsomes for doping control. (PubMed, Drug Test Anal) - "Neither sulfonic acid nor glucuronic acid conjugated metabolites were observed in this study. Data reported here could aid in the detection of non-steroidal selective androgen receptor modulator - GSK2881078 and reveal its illicit use in competitive sports."

Journal

Selective androgen receptor modulation for muscle weakness in chronic obstructive pulmonary disease: a randomised control trial. (PubMed, Thorax) - P2a | "GSK2881078 was well tolerated and short-term treatment increased leg strength, when expressed as per cent predicted, in men with COPD more than physical training alone."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Identification of equine in vitro metabolites of seven non-steroidal selective androgen receptor modulators for doping control purposes. (PubMed, Drug Test Anal) - "The equine metabolism of GSK-2881078, LGD-2226, LGD-3303 and PF-06260414 is reported for the first time. Although the equine metabolism of ACP-105, RAD-140 and S-23 has previously been reported, the results obtained in this study have been compared with published data."

Journal • Preclinical

Simultaneous detection of different chemical classes of selective androgen receptor modulators in urine by liquid chromatography-mass spectrometry-based techniques. (PubMed, J Pharm Biomed Anal) - "In detail, 19 target compounds belonging to 9 different chemical classes were considered: arylpropionamide (i.e., andarine (S4), ostarine (S22), S1, S6, S9 and S23), diarylhydantoin (i.e., GLPG0492), indole (i.e., LY2452473, GSK2881078), isoquinoline-carbonyle (i.e., PF-02620414), phenyl-oxadiazole (i.e., RAD140), pyrrolidinyl-benzonitrile (i.e., LGD4033), quinolinone (i.e., LGD2226, LGD3303), steroidal (i.e., Cl-4AS-1, MK0773 and TFM-4AS-1), and tropanol (i.e., AC-262536 and ACP105) derivatives. Urine samples containing andarine, ostarine, or LGD4033 were used to confirm the actual applicability of the selected analytical strategies. All target compounds (parent drugs and their main metabolites) were detected and correctly identified."

Journal

Detection of the selective androgen receptor modulator GSK2881078 and metabolites in urine and hair after single oral administration. (PubMed, Drug Test Anal) - "In conclusion, measurement of the intact compound GSK2881078 is feasible for both urine and hair analysis. However, concentrations in hair after single oral administration are in the low pg/mg-range and can only be detected, if the segments cover the administration period."

Journal

GSK delivers Q2 sales of £7.6 billion -2% AER, -3% CER (Pro-forma -10% CER*) (GSK Press Release) - "GSK’078 for COPD muscle weakness was terminated as data did not support progression in this indication....Initial data of the proof-of-concept study on the COPD candidate vaccine showed it did not meet the primary endpoint. Work is ongoing to better understand the data; no progression to Phase III is planned."

Discontinued • Chronic Obstructive Pulmonary Disease

Study to Evaluate the Safety and Efficacy of 13 Weeks of the Selective Androgen Receptor Modulator (SARM) GSK2881078 in Chronic Obstructive Pulmonary Disease (COPD) (clinicaltrials.gov) - P2a; N=97; Completed; Sponsor: GlaxoSmithKline; Active, not recruiting ➔ Completed

Clinical • Trial completion

Comparison of the three SARMs RAD-140, GLPG0492 and GSK-2881078 in two different in vitro bioassays, and in an in silico androgen receptor binding assay. (PubMed, J Steroid Biochem Mol Biol) - "Molecular modeling of the binding to the androgen receptor ligand binding domain suggests slight differences in the binding modes of RAD-140, GSK-2881078 and GLPG0492. In conclusion, androgenic activity of the three non-steroidal compounds in the two different in vitro test systems confirmed the results of the in silico modeling of the androgen receptor binding."

Journal • Preclinical

Study to Evaluate the Safety and Efficacy of 13 Weeks of the Selective Androgen Receptor Modulator (SARM) GSK2881078 in Chronic Obstructive Pulmonary Disease (COPD) (clinicaltrials.gov) - P2a; N=100; Active, not recruiting; Sponsor: GlaxoSmithKline; Recruiting ➔ Active, not recruiting; Trial completion date: Apr 2020 ➔ Dec 2019

Clinical • Enrollment closed • Trial completion date

Study to Evaluate the Safety and Efficacy of 13 Weeks of the Selective Androgen Receptor Modulator (SARM) GSK2881078 in Chronic Obstructive Pulmonary Disease (COPD) (clinicaltrials.gov) - P2a; N=100; Recruiting; Sponsor: GlaxoSmithKline; Trial completion date: Nov 2019 ➔ Apr 2020

Clinical • Trial completion date