EXSCALATE4COV: Italian Medicines Agency (AIFA) authorizes Raloxifene Clinical Trial for Paucisymptomatic Covid-19 Patients treated at Home and in Medical Facilities


The study, led by the National Institute for Infectious Diseases “L. Spallanzani” in Rome, Italy, will assess the safety and efficacy of raloxifene in paucisymptomatic patients infected by the Sars-CoV-2 virus. The Clinical Trial also involves the IRCSS Humanitas in Milan.

A patent on the use of raloxifene for the treatment of people affected by Sars-CoV-2 virus was filed on May 6, 2020 by Dompé farmaceutici, Fraunhofer Institute and Leuven University to promote universal access to related therapies that may be developed, in line with Exscalate4Cov’s guidelines.

Exscalate4CoV[1](E4C) is a transnationalpublic-private consortium, supported by EU’s Horizon2020 program for countering the coronavirus pandemic and developing new treatments.

The Italian Medicines Agency, AIFA, has greenlighted a clinical trial with a raloxifene product in patients with mild symptoms caused by the infection of the SARS-CoV-2 virus.

The study, promoted by the Exscalate4Cov public-private consortium and submitted to AIFA by Dompé farmaceutici as coordinator of the E4C project, will take place at the National Institute for Infectious Diseases “L. Spallanzani” in Rome, Italy, which is leading the study. The clinical trial also involves the IRCSS Humanitas in Milan. The extension of the clinical trial to other centers in Italy and in other countries is also being planned.

The clinical trial will study the safety and efficacy of raloxifene in inhibiting the replication of the Sars-Cov-2 virus. Enrollment in the study is expected to last 12 weeks. The study is adaptive and up to 450 participants can receive a 7 day treatment of raloxifene oral capsules or placebo.

Raloxifene is a registered molecule used in commercial prescription drugs for the treatment and prevention of osteoporosis in post-menopausal women. A patent on the use of raloxifene as a treatment of COVID-19 patients was filed on May 6, 2020 by Dompé Pharmaceuticals, Fraunhofer Institute and the University of Leuven in order to promote universal access to treatment as defined by the guidelines of the E4C consortium. It is important to remark that there is no evidence so far of a positive benefit/risk ratio of the molecule in treating Sars-CoV-2 infections, nor on the dosage to be used. For these reasons, raloxifene is not authorized for use in this indication outside of a clinical study.

The clinical trial marks the completion of the first phase of the Exscalate4CoV project which has screened 400,000 compounds (already approved drugs and natural products which are safe in humans) and specifically tested 7,000 molecules in vitro. So far, all data generated by E4C (10 peer reviewed articles and 10 additional articles submitted), the evidence from over 20,000 in vitro experiments as well as a virtual model of the sars-CoV-2 virus, have been made openly available to the international scientific community through the portal: www.mediate.exscalate4cov.eu. The International Journal of Molecular Scienceshas dedicated a special issue to the E4C project where it is possible to find the scientific production of the consortium.

The EXSCALATE4COV consortium has already identified other two safe in man drugs amenable for repurposing in COVID-19. The further characterization and validation of the efficacy and safety of these molecules will support the design of novel clinical trials.

At the core of E4C is Exscalate (EXaSCale smArt pLatform Against paThogEns), at present the most powerful[2](and cost-efficient) intelligent supercomputing platform in the world developed by Dompé farmaceutici. The aim of E4C is twofold: to identify molecules capable of targeting the new coronavirus (SARS-CoV-2) and to develop a tool effective for countering future pandemics. Exscalate leverages a chemical library of 500 billion molecules, applying a processing capacity of more than 3 million molecules per second. E4C’s screening process is supported by massive supercomputing resources for more than 100 Petaflops from four major EU machines: Cineca’s Marconi - 150 Petaflops; ENI’s HPC5 - 51,7 Petaflops, and Barcelona Supercomputing Center’s MareNostrum4 -13.7 Petaflops, Julich’s Juwels - 7 Petaflops with some of the continent’s best computational and life-science research labs.

The European Commission supported the E4C Consortium with 3 million euros from the EU’s Horizon 2020 research and innovation program under grant agreement No. 101003551.

[1] The Exscalate4Cov (www.exscalate4cov.eu) consortium, supported by the the EU’s Horizon 2020 programme for research and innovation, is coordinated by Dompé farmaceutici, and composed by 18 member institutions from seven European countries: Politecnico di Milano (Dept. of Electronics, Information and Bioengineering), Consorzio Interuniversitario CINECA (Supercomputing Innovation and Applications), Università degli Studi di Milano (Department of Pharmaceutical Sciences), International Institute of Molecular and Cell Biology in Warsaw (Warsaw, Poland), KU Leuven, Elettra Sincrotrone Trieste, Fraunhofer Institute for Molecular Biology and Applied Ecology, BSC Barcelona Supercomputing Centre, Forschungszentrum Jülich, Università Federico II di Napoli, Università degli Studi di Cagliari, SIB Swiss Institute of Bioinformatics, KTH Royal Institute of Technology (Department of Applied Physics), Associazione Big Data, Istituto Nazionale di Fisica Nucleare (INFN), Istituto nazionale per le malattie infettive Lazzaro Spallanzani and Chelonia Applied Science.- https://www.exscalate4cov.eu/consortium.html

E4C’s League of associated parties includes: ENI, Alfasigma, CFEL Center for Free-Electron Laser Science, MMV Medicines for Malaria Ventures, Esteve Pharmaceutical, University of Basel Biozentrum, University of Basel Innovation Office, University of Basel Department of Pharmaceutical Sciences, D-wave, Pierre fabre, Greenpharma, University of Sheffield - Sheffield Institute for Translational Neuroscience – SITraN, Dassault Systemes- Biovia, Institute of Food Science Research, CECAM Centre Européen de Calcul Atomique et Moleculaire, Nanome, Esteco, IT4Innovation, Università degli Studi della Tuscia, Sofia University “St. Kl. Ohridski”, Faculty of Physics, Institut Cochin- https://www.exscalate4cov.eu/league.html

[2] This performance exceeds by far the current "state of the art" technology which is also the subject of a recent article in Nature (6 February 2019, https://www.nature.com/articles/s41586-019-0917-9https://www.nature.com/articles/s41586-019-0917-9(www.nature.com/articles/s41586-019-0917-9) whereby a "chemical library" of 138 million molecules of a single target has been reached, with a processing capacity of less than 2 thousand molecules per second.

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