Background_x000D_
BIO101 (20-hydroxyecdysone) is an oral investigational drug activating Mas receptor, part of the renin-angiotensin system involved in the regulation of muscle metabolism and structure and pathophysiology of Covid-19. Here we present the results of 2 clinical trials evaluating safety and efficacy of BIO101 administered orally in 2 vulnerable populations: sarcopenic and hospitalized severe COVID-19 patients._x000D_
Methods_x000D_
SARA-INT: a randomized 3-arm study (BIO101 2 doses / placebo) with treatment for 6/9 months. Eligibility criteria for sarcopenia: FNIH criteria and SPPB score ≤ 8/12 in older adults. Primary endpoint: 400-meter walking test (400MWT). _x000D_
COVA: a randomized phase 2/3 trial. Hospitalized adults ≥45 years with respiratory symptoms from SARS-CoV-2 were randomized 1:1 to placebo or BIO101 350 mg bid, up to 28 days. Primary endpoint: proportion of patients dying or requiring high-flow oxygen, mechanical ventilation or ECMO (negative events)._x000D_
Results _x000D_
Despite COVID-19 pandemic, BIO101 showed promising results in sarcopenia on physical performance (0.07 m/s improvement in the 400MWT gait speed in the FAS population (not significant) and 0.09 m/s in the PP population (p=0.008); close to the MCID (0.1 m/s). Efficacy of BIO101 was also observed in pre-defined sub-populations (slow walkers, chair stand sub-score ≤2 from SPPB). COVA trial showed a statistically significant difference favouring BIO101 at D28 (BIO101: 15.8%, placebo: 26.0%), adjusted difference -11.4% (p=0.042), a relative risk (RR) reduction of negative events of 44%. _x000D_
In both studies, safety of BIO101 was good: less patients in BIO101 group experienced adverse events compared to placebo. _x000D_
Conclusion _x000D_
BIO101 350 mg bid is a candidate to treat vulnerable populations, with meaningful efficacy data and good safety. These data on respiratory and skeletal muscle function support the potential of BIO101 in treating DMD patients. With an ODD granted (US and EU), Biophytis intends to start a clinical development in non-ambulatory DMD patients in 2024.