Brazil Ministry of Health, HCFMUSP, São Paulo, Brazil

The COVA clinical program (clinicaltrials.gov identifier NCT04472728) is a Phase 2/3, randomized, double-blind, placebo-controlled, adaptive and group sequential study assessing Sarconeos (BIO101) in patients aged 45 and older, infected with SARS-CoV-2. It is designed to evaluate the efficacy and the safety of Sarconeos (BIO101) as a treatment to prevent further deterioration in patients with COVID-19-related respiratory failure. The objective is to prevent them from being admitted to the intensive care unit (ICU) and requiring ventilation.

Secondary endpoints include records of improvement, worsening and hospital discharge, functional scales and the biomarkers associated with the mechanism of action of Sarconeos (BIO101) and inflammation.

Sarconeos (BIO101), Biophytis leading drug candidate, is a small molecule, administered orally, currently in clinical Phase 2b in sarcopenia (SARA-INT) in the United States and Europe. A pediatric formulation of Sarconeos (BIO101) is being developed for the treatment of Duchenne Muscular Dystrophy (DMD). The company plans to start the clinical development (MYODA) in H2 2020.

Sarconeos (BIO101) is also being developed as a treatment for patients with COVID-19 related respiratory failure

As of December, 1st, 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, resulted in more than 2 972 917 deaths worldwide and death toll is still increasing exponentially. Many COVID-19 infected people are asymptomatic or experience moderate symptoms and recover without medical intervention. However, older people and those with comorbid hypertension, diabetes, obesity, or heart disease are at higher risk of mortality. Because current therapeutic options for COVID-19 patients are limited specifically for this elderly population at risk, Biophytis is developing BIO101 (20-hydroxyecdysone, a Mas receptor activator) as a new treatment for managing patients with SARS-CoV-2 infection at the severe stage.

Indeed, MasR activation by 20-hydroxyecdysone harbours anti-inflammatory, anti-thrombotic, and anti-fibrotic properties. BIO101, a 97% pharmaceutical grade 20-hydroxyecdysone could then offer a new therapeutic option by improving the respiratory function and ultimately promoting survival in COVID-19 patients that develop severe forms of this devastating disease. Therefore, the objective of this COVA study is to evaluate the safety and efficacy of BIO101, whose active principle is 20-hydroxyecdysone, in COVID-19 patients with severe pneumonia.

Covid-19 has completely transformed the society on a global scale and has had a devastating effect particularly on the frail elderly. Biophytis is very eager to answer the calls from it's industry, as well as national and international organizations to join the global effort to fight this pandemic.

The COVA study evaluates the therapeutic efficacy and the safety of Sarconeos (BIO101) as a treatment to prevent further respiratory deterioration in patients who experience severe respiratory manifestations due to COVID-19.

The Coronavirus SARS-CoV-2 can cause Acute Respiratory Distress Syndrome (ARDS) by disrupting the renin angiotensin system (RAS), which has a key role in regulating respiratory function. It is believed that SARS-CoV-2 enters the lung cells using the Angiotensin 2 Converting Enzyme (ACE-2), a key enzyme in the RAS, inhibiting the system’s protective arm.

Sarconeos (BIO101) activates the MAS receptor, a key component of the protective arm of the RAS, and has been shown to significantly improve respiratory function in several preclinical models.

Sarconeos (BIO101) is a drug candidate that has demonstrated a good safety profile during the SARA development program which is evaluating its ability to improve muscle function in frail elderly patients with sarcopenia (the phase 2b study, SARA-INT, is currently underway). Sarconeos (BIO101) is also being developed to improve the respiratory function of children with Duchenne muscular dystrophy (DMD). COVA is based on clinical and preclinical data from Sarconeos (BIO101) in these neuromuscular diseases.

Full protocol

The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Credits

Universidade de São Paulo Instituto do Coração, São Paulo, SP, Brasil