Dompé farmaceutici S.p.A (“Dompé”) today announced positive results from two studies demonstrating that treatment with oral raloxifene, a selective estrogen receptor modulator (SERM) with a proven safety profile, may be effective against SARS-CoV-2, including its clinically relevant variants. The two studies were conducted in collaboration with the Italian National Institute for the Infectious Diseases “Lazzaro Spallanzani” in Rome and other important clinical and preclinical research groups highly committed to COVID-19 research. “The clinical results on raloxifene published on Lancet’s eClinical Medicine[1] show a significant virological impact in term of negative nasopharyngeal swab at day 7 in COVID-19 patients treated at home with raloxifene compared to standard of care. This randomized clinical trial confirm the in vitro data published in Nature’s Cell Death and Disease[2], on the efficacy of Raloxifene on cellular lines experimentally infected by SARS-CoV-2” said Emanuele Nicastri, author of both studies and Director of the Infectious and Tropical Diseases Unit of the Spallanzani Institute in Rome, where Italy’s very first Covid-19 patients were hospitalized.
Raloxifene was identified by the Exscalate4CoV[3] (E4C) project, a group composed of 30 public and private institutions from seven countries and funded by EU Commission’s in the frame of its Horizon 2020 Framework Programme[4], aimed at fighting Coronavirus with the latest European supercomputing resources and experimental facilities. Results were driven by the use of Exscalate, Dompé’s supercomputing platform which leveraged a database of 500 billion molecules to find those capable of targeting clinically relevant coronavirus variants. Due to its processing capacity of more than 3 million molecules per second, Exscalate is currently the most powerful intelligent supercomputing drug design platform. This processing power allowed the E4C researchers to rapidly select and repurpose a generic molecule with known efficacy and tolerability to make it available to the global community. As raloxifene is a generic molecule already tested and approved for the treatment of osteoporosis, this was a not for profit effort aimed at providing a globally available low cost treatment.
The first study on raloxifene, published in The Lancet’s eClinical Medicine, demonstrated that after seven days of treatment, patients taking raloxifene showed an improvement in symptoms compared to patients receiving placebo (please refer to www.clinicaltrials.gov for additional clinical trial details). The second study, published in Cell Death and Disease), indicates raloxifene as a potential agent to treat mild-to-moderate COVID-19 caused by the most common SARS-CoV-2 variants. Mechanistic studies[5] confirmed the significant affinity of raloxifene for the Spike protein, as predicted by in silico studies. Researchers concluded that raloxifene is efficacious against the main SARS-CoV-2 variants and could represent a useful addition to the therapeutic arm for the management of Covid-19.
“Supercomputing is already demonstrating its potential for finding new solutions at previously unprecedented speeds in many domains, including medicine. I am very pleased that the Commission has supported the Exscalate4Cov consortium to discover promising treatments for COVID-19, and we now look forward to seeing the results of the consortium’s successor LIGATE project[6], which is developing a new drug discovery platform with the support of the European High Performance Computing Joint Undertaking” commented Thomas Skordas, Deputy Director-General of the European Commission’s Directorate-General for Communications Networks, Content and Technology (DG CONNECT).
“All of us at Dompé are incredibly proud of our contribution to the identification of new solutions to reduce the impact of COVID-19 on patients, healthcare systems, and their communities” said Marcello Allegretti, Chief Scientific Officer at Dompé. “The huge power of our unique supercomputing platform has been a gamechanger, but we want to thank all patients and researchers around the world who participated in these two studies. These results show the importance of combining pharmacological knowledge and breakthrough technologies as AI tools, to exploit the potential of repurposed drugs, and to elevate understanding of yet to be revealed mechanisms of action to address critically unmet medical needs“.
