Oratrope (ibutamoren) / Merck (MSD), Lumos Pharma - LARVOL DELTA

Acute stress suppresses hunger-driven food seeking through PVN activation: Reversal by anxiolytic drug and ghrelin receptor agonist, with anxiolytic-like effects of refeeding. (PubMed, Neurosci Res) - "Acute restraint abolished fasting-induced increases in food seeking and intake, an effect that was reversed by intraperitoneal diazepam, an anxiolytic, and by MK-677, a ghrelin receptor agonist that enhances appetite. Notably, refeeding after fasting induced a similar pPDH-dominant pattern and attenuated stress-induced anxiety-related behaviors, indicating that restoration of energy balance exerts intrinsic anti-stress effects through PVN inhibition. Together, these findings reveal that acute stress suppresses hunger-driven food seeking via PVN activation, pharmacological inhibition reverses this suppression, and physiological refeeding promotes stress resilience via PVN-medicated inhibition, highlighting PVN modulation as a shared mechanism linking emotional and metabolic homeostasis."

Journal • Mood Disorders • Psychiatry • FOS

LUM-201 Augments Weight & Fat Tissue Loss While Preserving Lean Mass in GLP-1 Treatment of DIO Mice (OBESITY WEEK 2025) - "LUM-201 used in combination with semaglutide augments the efficacy of single-agent semaglutide for treatment of diet-induced obesity in mice. The combination of LUM-201 dosed + semaglutide improves weight loss compared with semaglutide solo. Importantly, the combination also preserves lean muscle mass in the context of weight loss compared with single-agent semaglutide.More broadly considered, these findings suggest that combining LUM-201 with GLP-1 receptor agonists could augment the health benefits of GLP-1 receptor agonists by enhancing weight loss while concurrently preserving lean muscle mass."

Preclinical • Genetic Disorders • Obesity

Phase 2 Study of LUM-201 in Children Who Have Previously Completed the LUM-201-01 Trial (OraGrowtH213) (clinicaltrials.gov) - P2 | N=18 | Completed | Sponsor: Lumos Pharma | Active, not recruiting ➔ Completed

Trial completion • Endocrine Disorders • Growth Hormone Deficiency • IGF1

Phase 3 Study of LUM-201 in Children With Growth Hormone Deficiency (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Lumos Pharma | Not yet recruiting ➔ Recruiting

Enrollment open • Endocrine Disorders • Growth Hormone Deficiency

Knowing the minimal detectable dose can facilitate the interpretation of a hair test result: II. Case example with ibutamoren (MK-677), a growth hormone secretagogue. (PubMed, Clin Chim Acta) - "The interpretation of the findings of ibutamoren in human hair can be established in the light of these new data as the minimal detectable dose has been established, as well as the range of concentrations after a regimen of 60 days for performance enhancement."

Journal

Phase 3 Long Term Safety Extension Study of LUM-201 in Children With Growth Hormone Deficiency (clinicaltrials.gov) - P3 | N=150 | Not yet recruiting | Sponsor: Lumos Pharma

New P3 trial • Endocrine Disorders • Growth Hormone Deficiency

The Impact of the Oral Growth Hormone Secretagogue Ibutamoren on Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Adults With Overweight/Obesity (ENDO 2025) - P2 | "In this pilot study, we demonstrated a possible beneficial signal of ibutamoren on IHL in an as-treated secondary analysis but were unable to demonstrate this effect in our primary analysis or an effect on body composition in either analysis. Future larger studies could investigate oral ibutamoren co-administered with weight loss medications such as GLP-1 receptor agonists, a combination which may offset the negative glycemic effect of ibutamoren while harnessing the potential for GH augmentation to further reduce liver fat and preserve muscle mass."

Clinical • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • IGF1

Phase 3 Randomized and Double-blinded Trial Design with LUM-201 vs Placebo to Evaluate the Efficacy and Safety of this Daily Oral Growth Hormone Secretagogue in Treatment-Naïve Children with Growth Hormone Deficiency (GHD) (ENDO 2025) - "By stimulating endogenous GH release via the GH-releasing hormone pathway and reducing somatostatin activity, LUM-201 preserves the physiological feedback loop, distinguishing it from exogenous GH injections. The OraGrowtH Phase 3 trial aims to further evaluate LUM-201's efficacy and safety as an oral treatment for GHD."

Clinical • P3 data • Endocrine Disorders • Growth Hormone Deficiency • Pediatrics • IGF1

Ibutamoren Mesylate, an Oral Growth Hormone (GH) Secretagogue, Modifies Body Composition in Healthy Older Adults by Increasing Both the Amount and the Pattern of Endogenous GH Secretion (ENDO 2025) - "This analysis indicates both the amount and the variation in GH secretion in healthy older adults treated with IB influences changes in body composition, in both for the 12hr day-time GH secretion and for the full 24hr profile. These effects of Ibutamoren on physiological GH secretion reinforce the importance of pulse profiles to GH action."

Clinical • Growth Hormone Deficiency • Growth Hormone Deficiency (Adult) • Sarcopenia

Higher Order Time Series Interactions Within The Growth Hormone (GH) Secretion Profile Mark Growth Responsiveness Induced By The Oral Growth Hormone Secretagogue Lum-201 (ENDO 2025) - "ESPE (2024), FC15.2 3. Carletti et al 2020.Physical review E, p.022308"

Late-breaking abstract • Growth Hormone Deficiency • Growth Hormone Deficiency (Pediatric) • Pediatrics

Oral Growth Hormone Secretagogue (LUM-201) Pediatric Capsule Formulation Demonstrates Similar Pharmacokinetic (PK) Bioavailability and Pharmacodynamic (PD) Responses to Current Tablet Formulation (ENDO 2025) - "No significant differences in PK or PD were observed in comparisons of fasted versus fed state. Thus, regardless of formulation or administration method, the immediate GH release stimulated by LUM-201 results in similar GH Cmax values."

Clinical • PK/PD data • Pediatrics • IGF1

Hepatotoxicity induced by MK-677. (PubMed, BMJ Case Rep) - "Here we present the case of an otherwise healthy man in his early 30s, who developed transaminitis after consuming MK-677 for 2 months before presentation. Liver function tests eventually returned to normal limits after stopping the supplement."

Journal • Hepatology • Musculoskeletal Pain • Pain

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

LUM-201 Treatment of Pediatric GHD over 24 Months Demonstrates Sustained Increases in Growth with Early Increases in IGF-1 and BMI That Stabilize Within the Normal Range: OraGrowtH210 Trial Update (ESPE-ESE 2025) - No abstract available

Clinical • Late-breaking abstract • Pediatrics • IGF1

The Effect of the Oral Growth Hormone (GH) Secretagogue LUM-201 on the Pattern of GH Secretion in Pediatric GH Deficiency (GHD): Identification of Higher Order Interactions within the GH Profile (ESPE-ESE 2025) - "In response to LUM- 201, there are shifts in the pattern of GH: more subjects had GH levels above the median in the early in-phase part of the profile and less in the late part, and less in the out-of-phase mid and late parts of the profile. These complex interactions are likely to contain additional functional signals related to GH action, which now need to be linked to clinical outcomes."

Clinical • Late-breaking abstract • Growth Hormone Deficiency • Growth Hormone Deficiency (Pediatric) • Pediatrics

LUM-201 Treatment of Pediatric GHD over 24 Months Demonstrates Sustained Increases in Growth with Early Increases in IGF-1 and BMI That Stabilize Within the Normal Range: OraGrowtH210 Trial Update (ESPE-ESE 2025) - "No safety signals of concern have been identified. Oral LUM-201 may provide an innovative way to treat moderate GHD."

Clinical • Late-breaking abstract • Endocrine Disorders • Growth Hormone Deficiency • Growth Hormone Deficiency (Pediatric) • Pediatrics • IGF1

Phase 3 Pivotal Trial Design of Daily Oral LUM-201’s Efficacy and Safety in Treatment-Naïve Children with Growth Hormone Deficiency (GHD) in Randomized, Double-blind, Placebo-controlled Study (ESPE-ESE 2025) - "By stimulating endogenous GH release via the GH-releasing hormone pathway and reducing somatostatin activity, LUM-201 preserves the physiological feedback loop, distinguishing it from exogenous GH injections. The OraGrowtH Phase 3 trial aims to further evaluate LUM-201’s efficacy and safety as an oral treatment for GHD."

Clinical • P3 data • Endocrine Disorders • Growth Hormone Deficiency • Pediatrics • IGF1

Evaluation of the Pharmacokinetics (PK), Pharmacodynamics (PD), and Safety of the New Capsule Formulation of LUM-201, an Oral Growth Hormone Secretagogue (ESPE-ESE 2025) - "Conclusions Overall, the study demonstrated that the new capsule formulation of LUM-201 has a favorable investigational safety profile, is well-tolerated, and exhibits comparable bioavailability to the tablet formulation, with consistent PK parameters for the metabolite M8 and encouraging PD responses. The new LUM-201 capsule formulation filled with mini-tablets produces similar PK and PD results compared with the current tablet formulation and offers children & their caretakers a more flexible and user-friendly oral capsule formulation."

Clinical • PK/PD data • IGF1

Phase 3 Study of LUM-201 in Children With Growth Hormone Deficiency (clinicaltrials.gov) - P3 | N=150 | Not yet recruiting | Sponsor: Lumos Pharma

New P3 trial • Endocrine Disorders • Growth Hormone Deficiency

The Impact of Ibutamoren on Nonalcoholic Fatty Liver Disease (clinicaltrials.gov) - P2 | N=13 | Completed | Sponsor: Massachusetts General Hospital | Active, not recruiting ➔ Completed

Trial completion • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • IGF1

Design, Biological Characterization, and Discovery of Capromorelin Derivatives as Oral Growth Hormone Secretagogue Receptor Type 1a Agonist for the Treatment of Growth Hormone Deficiency. (PubMed, J Med Chem) - "Starting from capromorelin, we designed, synthesized, and characterized a novel orally active GHSR-1a agonist, compound 4b (hGHSR-1a EC50 = 0.49 nM), which effectively stimulates endogenous GH release in rats at oral doses as low as 0.1 mg/kg─100-fold more potent than ibutamoren (10 mg/kg)...Compound 4b exhibited superior pharmacokinetic exposure in dogs (oral bioavailability: 43.6%; half-life: 1.2 h) relative to other species. This study details the optimization of 4b, which demonstrates a promising pharmacological profile for clinical translation as a growth hormone replacement therapy."

Journal • Endocrine Disorders • Growth Hormone Deficiency

Intranasal delivery of a ghrelin mimetic engages the brain ghrelin signalling system in mice. (PubMed, Endocrinology) - "Additionally, intranasal GHRP-6 elevated GH serum levels. These findings suggest that intranasal GHRP-6, but not ghrelin or MK-0677, can engage the brain ghrelin signalling system."

Journal • Preclinical • FOS

Investigating the P53-dependent anti-cancer effect of ibutamoren in human cancer cell lines. (PubMed, Basic Clin Pharmacol Toxicol) - "This trend was further supported by RT-qPCR analysis, which showed differential expression of two p53 target genes upon IBU treatment in cell lines with wild MDM2-p53 pathways but not in those harbouring damaging mutations. These findings provide preliminary evidence supporting IBU's anticancer activity, plausibly through the MDM2-p53 pathway, and suggest that further studies are warranted to explore its mechanism of action and potential development as a lead compound in oncology research."

Journal • Preclinical • Oncology • Targeted Protein Degradation

Amount and Pattern Of Pulsatile GH Secretion Induced By The Oral Growth Hormone Secretagogue LUM-201 Is Related To Growth And IGF-1 Responses In Moderate Pediatric Growth Hormone Deficiency (PGHD) (ESPE 2024) - "In response to oral LUM-201, pulsatile GH secretion, growth rate and serum IGF-1 increased. Additionally, LUM-201 induced both an increase in disorderliness (ApEn) of the pulse profiles and an alteration in time periods at which the greatest variation occurred, which differed between high and lower growth responders. Both amount and pattern of GH secretion are important for growth and IGF-1 responses to LUM-201."

Clinical • Late-breaking abstract • Endocrine Disorders • Growth Hormone Deficiency • Growth Hormone Deficiency (Pediatric) • Pediatrics • IGF1

Growth, IGF-1 and IGFBP-3 Responses to Oral LUM-201 in OraGrowtH210 and OraGrowtH212 Trials in Pediatric Growth Hormone Deficiency (PGHD) over 12 to 24 Months on Treatment (ESPE 2024) - "LUM-201 in prepubertal moderate PGHD increases AHVs to above the 50th centile for age and sex. Preliminary data suggest such growth rate can be maintained to 24m, with lower fall-off in AHV in the second year compared to that seen with rhGH. Serum IGF-I and IGFBP-3 are increased, with IGF-I levels lower than those induced by rhGH."

Clinical • Endocrine Disorders • Growth Hormone Deficiency • Growth Hormone Deficiency (Pediatric) • Pediatrics • IGF1 • IGFBP3 • SORL1