ABSTRACT
Sarcopenia is a progressive muscle disorder increasing with age that may lead to mobility disability. SARA program strives to develop a viable option to treat community dwelling older adults suffering from sarcopenia. SARA-INT is a randomized three-arm interventional study (BIO101 175 mg bid / BIO101 350 mg bid / placebo) with treatment duration of 6 months. Eligibility criteria for sarcopenia were meeting FNIH criteria and Short Physical Performance Battery (SPPB) score ≤ 8/12 in men and women aged ≥ 65 years;primary endpoint was the 400-meter walking test (400MWT). 233 participants aged 65 years and older were randomized, 232 and 156 participants were included in the Full Analysis Set (FAS) and Per-Protocol (PP) populations, respectively. Due to COVID-19 pandemic, most end-of-treatment efficacy assessments are missing for 55% of the participants, reducing the studies' power. BIO101 350 mg bid treatment led to an improvement in the primary endpoint, the gait speed from the 400MWT of 0.07 m/s in the FAS population (not statistically significant) and of 0.09 m/s in the PP population (nominally statistically significant, p=0.008) after 6 months;this is close to MCID in sarcopenia (0.1 m/s). BIO101 350mg bid treatment effect on the 400MWT is confirmed in PP sub-populations at high risk of mobility disability. Trends were observed with other endpoints. BIO101 showed a very good safety profile at both doses. Biophytis will initiate the phase 3 program by end 2022, targeting a severe sarcopenic population. Outcomes of the interactions with regulatory agencies on study design will be presented.
ABSTRACT
Backgrounds: Sarcopenia is a geriatric condition characterized by a progressive loss of muscle mass and function, having high personal, social and economic burdens when untreated. Sarcopenia increases risk of falls and fractures;impairs ability to perform activities of daily living;is associated with cardiac and respiratory disease and cognitive impairment;leads to mobility disorders;and contributes to lowered quality of life, loss of independence or need for long-term care placement, and death. It is recognized as one of the five pillars of frailty. As of today, to our knowledge, only exercise and nutrition interventions seem somewhat effective interventions. Objectives: SARA-INT study is a Phase 2 study to develop a viable option to treat community-dwelling seniors suffering from age-related sarcopenia, including sarcopenic obesity. Methods: SARA-INT is a randomized double-blind three-arm study (BIO101 175 mg bid / BIO101 350 mg bid / placebo) with planned treatment duration of 6 Months;due to COVID-related measures, 49 patients continued up to 9 months of treatment. Main eligibility criteria for sarcopenia were meeting FNIH criteria and Short Physical Performance Battery (SPPB) score ≤ 8/12 in men and women aged ≥ 65 years. Primary analysis was the gait speed from the 400-meter walking test (400MWT) at month 6/9 in the FAS with secondary analyses at other timepoints, secondary endpoints were other physical activity assessments, muscle strength, muscle mass and Patient Reported Outcomes (PROs). Results: 233 participants were randomized in the study, 232 and 156 participants were included in the Full Analysis Set (FAS) and Per-Protocol (PP) populations, respectively. Due to COVID-19 pandemic, end-of-treatment assessments are missing for approximately half of the participants, impacting the treatment effect detection. In the primary analysis (at month 6/9 in the FAS population) of the primary parameter, the improvement in 400MWT compared to placebo was not statistically significant (0.0363 (0.03098) m/s and 0.0385 (0.02985) m/s in the BIO101 175 mg and 350 mg groups, p=0.2437 and p=0.2000, respectively). BIO101 350 mg bid treatment after 6 months showed a clinically relevant improvement in the 400MWT of 0.07 m/s in the FAS population (not significant) and of 0.09 m/s in the PP population (nominally statistically significant, p=0.008);this is close to the Minimal Clinically Important Difference (MCID) in sarcopenia (0.1 m/s). BIO101 350mg bid treatment effect on the 400MWT is confirmed in pre-defined sub-populations at higher risk of mobility disability such as slow walkers, obese and those with chair stand sub-score ≤2 from SPPB;trends were observed with other independent endpoints. BIO101 showed no difference in adverse events or safety laboratory parameters versus placebo (), and no severe adverse event associated with BIO101 treatment. Conclusions: After 6 to 9 months of treatment, BIO101 at 350 mg bid showed promising results with a clinically relevant improvement in the 400MWT gait speed, the primary endpoint of the study, confirmed in sub-populations at higher risk of mobility disability. BIO101 showed a very good safety profile at the doses of 175 and 350 mg bid. Biophytis is preparing to start a phase 3 program with BIO101 at 350 mg bid in 2022, targeting a similar patient population. Conflicts of interests: CT, WD, CM, RL, PD, RvM and SV are employees of Biophytis SA, AZ, and SA are employees of Biophytis Inc., JM is president of the Scientific Advisory Board of Biophytis, SDS is employee of BlueCompanion Ltd.