{"doi":"10.1002/jcsm.13750","title":"BIO101 in Sarcopenic Seniors at Risk of Mobility Disability: Results of a Double‐Blind Randomised Interventional Phase 2b Trial","abstract":"BACKGROUND: Sarcopenia is a progressive muscle disorder that may lead to mobility disability. No pharmaceutical interventions are currently available, and treatment relies on physical exercise and nutrition. The aim of SARA-INT was to investigate whether BIO101 (20-hydroxyecdysone), an activator of the MAS receptor, is safe and improves muscle function and physical performance of community dwelling older sarcopenic patients. METHODS: SARA-INT was a randomised three-arm interventional study (BIO101 175 mg bid /350 mg bid/placebo) with a planned 6-month treatment (up to 9 months in 50 subjects). Eligibility criteria for sarcopenia were meeting FNIH criteria for sarcopenia and Short Physical Performance Battery (SPPB) score ≤ 8/12 in men and women aged ≥ 65 years. Primary endpoint was the change from baseline (CFB) in gait speed (GS) measured by 400-m walking test (400MWT), secondary endpoints being CFB in other physical performance tests. RESULTS: A total of 233 participants were randomised (mean age 75.5 ± 7.12; 54.3% female), of whom 232 and 156 were included in the full analysis set (FAS) and per-protocol (PP) populations, respectively. Due to COVID-19 pandemic, 55% of on-site end-of-treatment efficacy assessments were lost, reducing the studies' power. In the primary analysis (mix of 6/9 months), BIO101 350 mg bid treatment after 6/9 months was associated with an improvement in the 400MWT of 0.07 m/s versus placebo in the FAS population (not significant) and of 0.09 m/s in the PP population (p = 0.008). BIO101 350 mg bid treatment effect on the 400MWT GS was also observed in pre-defined subpopulations at higher risk of mobility disability (0.0474 m/s for slow walkers, 0.0521 m/s for obese and 0.0662 m/s for chair stand sub-score ≤ 2 from SPPB in the FAS population), with a trend for a dose response. BIO101 showed a good safety profile at both doses (number of subjects with related treatment emergent adverse events (TEAEs) of 13 (16.0%), 10 (13.3%) and 10 (13.5%) in the placebo, 175 mg and 350 mg BIO101 groups, respectively). CONCLUSIONS: After 6 to 9 months of treatment, BIO101 350 mg bid showed strong trends consistent with a clinically relevant effect on the 400MWT GS, close to the minimal clinically important difference (MCID) in sarcopenia (0.1 m/s). This was also shown in predefined subpopulations at higher risk of mobility disability. BIO101 showed a good safety profile. Taken together, efficacy and safety data of this Phase 2 trial encourage us to pursue further development of BIO101 for the treatment of sarcopenia.","journal":"Journal of Cachexia Sarcopenia and Muscle","year":2025,"id":512800,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1373656,"name":"Michael Dao","orcid":null,"position":1,"is_corresponding":false},{"id":1373657,"name":"Kevin Cannon","orcid":null,"position":2,"is_corresponding":false},{"id":888926,"name":"Moı̈se Desvarieux","orcid":null,"position":3,"is_corresponding":false},{"id":1373658,"name":"Sam S. 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Kritchevsky","orcid":"0000-0003-3336-6781","position":12,"is_corresponding":false},{"id":665069,"name":"Nicolas Musi","orcid":"0000-0003-4242-2888","position":13,"is_corresponding":false},{"id":1373663,"name":"Joe M. Chehade","orcid":null,"position":14,"is_corresponding":false},{"id":1373007,"name":"Judith L. Kirstein","orcid":"0000-0001-9665-8525","position":15,"is_corresponding":false},{"id":1373008,"name":"Evelien Gielen","orcid":"0000-0002-8985-1201","position":16,"is_corresponding":false},{"id":616873,"name":"Paul Pickrell","orcid":null,"position":17,"is_corresponding":false},{"id":1373009,"name":"Pierre J. Dilda","orcid":"0000-0001-9916-8513","position":18,"is_corresponding":false},{"id":1373010,"name":"René Lafont","orcid":"0000-0002-8044-540X","position":19,"is_corresponding":false},{"id":1373664,"name":"Carole Margalef","orcid":null,"position":20,"is_corresponding":false},{"id":62712,"name":"Yves Rolland","orcid":"0000-0002-1157-0215","position":21,"is_corresponding":false},{"id":1373011,"name":"Susanna Del Signore","orcid":"0000-0002-1270-326X","position":22,"is_corresponding":false},{"id":869861,"name":"Jean Mariani","orcid":"0000-0002-2701-1581","position":23,"is_corresponding":false},{"id":1223220,"name":"Samuel Agus","orcid":null,"position":24,"is_corresponding":false},{"id":1133517,"name":"Cendrine Tourette","orcid":"0000-0002-3533-5412","position":25,"is_corresponding":false},{"id":1133516,"name":"Waly Dioh","orcid":"0000-0001-9481-028X","position":26,"is_corresponding":false},{"id":799715,"name":"Rob van Maanen","orcid":"0009-0007-1212-6697","position":27,"is_corresponding":false},{"id":1373012,"name":"Stanislas Veillet","orcid":"0000-0003-2772-6015","position":28,"is_corresponding":false},{"id":109419,"name":"Roger A. Fielding","orcid":"0000-0003-2236-9020","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T02:48:11.233009Z","pmid":"40026058","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}