Clinical Trials

Date: 2017-05-03

Type of information: Presentation of results at a congress

phase: 2a

Announcement: presentation of results at the International ICFSR

Company: Biophytis (France)

Product: Sarconeos (formerly SARCOB BIO101)

Action mechanism:

• Sarconeos is an orally available selective MAS receptor agonist, which has demonstrated efficacy in preclinical proof of concept studies. MAS receptor is a major player of the renin-angiotensin system) stimulating anabolism in the muscle.

Disease: sarcopenic obesity

Therapeutic area: Muscle disorders

Country: Belgium, France

Trial details:

• The objective of the SARA-PK study was to evaluate safety, tolerance and the pharmacokinetic profile of Sarconeos in healthy elderly volunteers (>65 years). The study was carried out in two phases: the administration of a single ascending dose (SAD), and multiple ascending doses (MAD). The second stage of the study – MAD (multiple ascending doses) had as its objective the evaluation of the safety, tolerance and pharmacokinetics of Sarconeos in subjects aged 30, after the oral administration of 3 multiple ascending doses (350mg/day, 700 mg/day then 900 mg/day) every day over 14 days.

Latest news:

• • On May 3, 2017, Biophytis announced it presented at the ICFSR the full results of Sarconeos (BIO101) in the SARA-PK clinical study. The analysis of pharmacodynamics data showed that some biomarkers of muscle metabolism or key hormones of the renin angiotensin system (RAS) were modulated in accordance with the mechanism of action of Sarconeos.  The analysis of pharmacodynamics data confirmed that observed changes on biomarkers of muscular metabolism (creatine kinase, myoglobin...) and of the renin-angiotensin system (renin, adolsterone...) are consistent with the mechanism of action of  Sarconeos, which stimulates anabolism in skeletal muscles through the activation of MAS receptor. The activation of MAS receptor stimulates protein synthesis and counteracts proteolysis in skeletal muscles thereby compensating the loss of muscle mass, muscle strength, and mobility losses associated with aging in animal models of Sarcopenia.
• • On March 1st, 2017, Biophytis announced complete results of the SARA-PK study. The analyses confirm the good pharmacokinetic profile in healthy elderly volunteers, the therapeutic window of Sarconeos, and confirms the dosages that will be tested in the Phase 2b trial SARA-INT. The study’s complete results will be presented at the International ICFSR on April 28th in Barcelona.
• The main parameters of the pharmacokinetics (half-life, area under curve, maximum plasma concentration of the product, etc) have been estimated, allowing the confirmation of Sarconeos’ good pharmacokinetic profile in healthy elderly volunteers, which is not significantly different from the profile observed in adult volunteers. The qualitative study of biomarkers of muscular metabolism (creatine kinase, myoglobin, etc) and of the renin-angiotensin system (renin, adolsterone, etc) gathered at the end of the trial, allows for the description of Sarconeos’ pharmacodynamic profile. The study of Sarconeos’ effects on these biomarkers in SARA-INT should allow the confirmation of these patterns.
• The complete analysis of the safety, pharmacokinetic and pharmacodynamic data allows the confirmation of Sarconeos’ favourable therapeutic window and the selection of the two doses which will be tested in the placebo-controlled Phase 2b SARA-INT trial, provided it is authorized by the relevant regulatory agencies. The selected oral doses are: 175 mg twice-daily and 350mg twice-daily.
• • On December 16, 2016, Biophytis announced that new preclinical and clinical data on Sarconeos (BIO101) have been presented at the 9th International Conference on Sarcopenia, Cachexia and Wasting Disorders in Berlin.
• Various experiments in human and mice myocytes demonstrated that the anabolic effects of Sarconeos in skeletal muscles result from an activation of Mas receptor, the receptor of Angiotensin 1- 7, a key component of the renin-angiotensin system, followed by the activation of AKT/mTOR, MAPK and AMPK pathways leading to the inhibition of myostatin gene expression.
• A new study in ageing mice demonstrated the potential of Sarconeos in improving skeletal muscle quality and in compensating the significant loss of mobility, as a consequence of ageing. An other study led in young mice submitted to chronic oral administration of Sarconeos, demonstrated higher protein content and a significant reduction of myostatin gene expression in skeletal muscles. The SARA-PK study completed in H2 2016 in adult and elderly volunteers (> 65 years old) confirmed the good safety profile of Sarconeos, with no severe adverse event recorded at the tested doses (up to 1400 mg/day).
• The pharmacokinetic profile is not significantly different between old and adults volunteers. Moreover, no food effect has been detected.
• • On November 29 2016, Biophytis announced the successful completion of its SARA-PK clinical study for Sarconeos. The results of the study, conducted in young and elderly healthy volunteers, confirmed Sarconeos’ appropriate safety profile, with no serious adverse events associated with the administration of Sarconeos. The results of the SARA-PK study will be used to select the two doses of Sarconeos for further evaluation in the Phase 2b SARA-INT trial, which Biophytis intends to initiate in the first half of 2017. The complete results of the SARA-PK study, in particular the pharmacokinetic profile of Sarconeos, will be available in the first quarter of 2017.
• • On September 22, 2016, Biophytis announced the successful completion of the SARA-PK SAD (Single Ascending Dose) portion of a pharmacokinetics study for  Sarconeos, being developed to treat sarcopenia. The objective of the SARA-PK study is to assess the safety, tolerability and pharmacokinetic profile of Sarconeos in elderly healthy volunteers (> 65 years old). The study is being conducted in two phases (single ascending dose (SAD) administration and multiple ascending dose (MAD) administration).
• The recently completed SAD portion of the study was aimed at comparing pharmacokinetics in elderly and young volunteers following escalating single dose administrations. No severe adverse event related to Sarconeos were reported following any of the four administered doses, ranging from 100 mg/day up to 1400 mg/day, in 24 young or old subjects enrolled.
• The SARA-PK MAD portion of the study is beginning now and will evaluate the safety and pharmacokinetics of Sarconeos in 30 older subjects, following multiple ascending oral administrations daily for 10 days. Data from the second portion of the study will be reported by the end of the year and will be used to select the two doses of Sarconeos for study in the Phase 2b SARA-INT trial, which is currently expected to begin in the first half of 2017.
• • On July 25, 2016, Biophytis announced that the Belgian regulator authorized the planned pharmacokinetics study of its lead product, Sarconeos (SARA-PK study), which is in development to treat sarcopenic obesity. The Belgian Federal Agency for Medicines and Health Products (FAMHP) and the Ethics Committee in Antwerp gave their authorization regarding the initiation of the SARA-PK study to qualify pharmacokinetics and safety of Sarconeos in elderly healthy volunteers (> 65 years old).
• This study will be conducted during the second half of 2016 in two phases: the first phase will compare pharmacokinetics in elder and young volunteers after escalating single dose administrations of Sarconeos; the second phase will study pharmacokinetics and safety on elder healthy volunteers (30 volunteers) after daily administrations of Sarconeos for 14 days, at 3 doses. The results of the study will complete the clinical and regulatory file for Sarconeos, which is required for authorization to initiate the Phase IIb “SARA INT” clinical study, currently scheduled to start in the first half of 2017 in France, Belgium, Italy and USA.
• • On March 11, 2016, Biophytis announced that it received scientific advice from the Belgian Federal Agency for Medicines and Health Products (FAHMP) regarding its clinical development plan for SARCOB BIO101, which is being studied for treatment of patients suffering from sarcopenic obesity (i.e. loss of muscle functionality in obese people).
• The FAHMP opinion was requested by Biophytis in November 2015 . It is the first step of the regulatory process by which Biophytis seeks to obtain approvals of several agencies (FAHMP, ANSM, EMA, FDA) necessary to proceed with a Phase 2B trial of SARCOB BIO101 in about 180 patients suffering from sarcopenic obesity, currently under preparation to be conducted in France and Belgium.
• The plan proposed by Biophytis includes a number of supplementary preliminary studies, among which a pharmacokinetics study after multiple administration in healthy older volunteers that will be conducted this summer in Belgium by SGS Life Science.

Is general: Yes