With upwards of 50 million confirmed cases in 217 countries, and a projected drop in global GDP of over $7 trillion this year, the world needs a COVID-19 solution and fast. Developing a targeted therapy or vaccine may be the “Holy Grail,” but this can be time consuming and costly. Sometimes the best solution is already sitting on the pharmacy shelf. This is the concept behind Solidarity—a global study managed by the World Health Organization (WHO) and led in Montreal by Matthew Cheng, MDCM’11, PGME’17.
“There are clear advantages to assessing the efficacy of the most promising drugs currently in existence,” explains Cheng, an assistant professor in the Ă山ǿĽé Department of Medicine. “These drugs, while not created for COVID-19, often have other indications and we already know they have a good safety profile because they have been tried and tested in humans.”
The WHO convened a group of experts to evaluate the most suitable medications for assessment, ranking them in terms of their probability of success against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—the virus that causes COVID-19. The top four contenders were remdesivir, previously tested as an Ebola treatment; hydroxychloroquine, used to treat rheumatologic conditions; lopinavir and ritonavir, used to treat HIV; and interferon, used to treat multiple sclerosis.
Despite any evidence that these drugs would benefit COVID-19 patients, they had quickly become household names after active promotion by the Trump administration. Interestingly, this increased level of public awareness seems to have made it easier to recruit patients for Solidarity. “People with COVID-19 were coming to the hospital asking for hydroxychloroquine and remdesivir,” recalls Cheng. “It was extraordinary.” At the height of the pandemic, four of every five COVID-19 patients hospitalized at the Ă山ǿĽé Health Centre (MUHC) were enrolled in the study, which is an extremely high participation rate according to Cheng. “Desperate times call for desperate measures,” he says. “COVID-19 is a scary disease with no treatment initially available and many patients were keen to try something beyond supportive care, and trial participation was the only other option available.”
Worldwide, Solidarity enrolled almost 12,000 patients at 500 hospital sites in over 30 countries, according to the WHO. “It wasn’t just the size of Solidarity that was unprecedented, it was also the speed at which the trial was launched and achieved definitive results,” says Cheng. The preliminary results were announced on October 15, 2020, just a few months after the study was launched. Unfortunately, the data showed that none of the four drugs had significant effects on mortality, initiation of ventilation or duration of hospital stay in hospitalized COVID-19 patients.
“It was disappointing—there’s no question we would have preferred a better result,” admits Cheng, who had hoped that at least one of these drugs would work for COVID-19, particularly remdesivir, which had shown early promise. “However, we have been able to definitively answer the question of their suitability for COVID-19 and that provides important insight.”
Solidarity doesn’t end there. “This virus isn’t stopping and neither are we,” says Cheng. “There is no shortage of other drug candidates to test as potential treatments, so we’ll keep going until we find something that works or we develop an effective vaccine.” An immune modulator called acalibrutinib has already been added to the trial. Researchers hope this drug will reduce the excess inflammation caused by the body during infection, thereby lessening the need for ventilators, shortening hospital stays and improving patient outcomes. The team is also planning to test two monoclonal antibodies, which are essentially lab-created versions of the antibodies that the human immune system might produce naturally to fight the pathogen.
The Ă山ǿĽé component of Solidarity was able to benefit from the donor-supported MI4 Emergency COVID-19 Research Funding program. Formally established in April 2018 thanks to a $15 million gift from Montreal’s Doggone Foundation, the Ă山ǿĽé Interdisciplinary Initiative in Infection and Immunity (MI4) is one of the largest grouping of experts focused on infectious and immune-mediated diseased in the world. It brings together more than 250 researchers from Ă山ǿĽé, the MUHC, the Jewish General Hospital and other clinical partners, as well as from affiliated research centres. “Ă山ǿĽé and the MUHC showed great foresight to set up MI4 before this pandemic began,” says Cheng. “Having this kind of infrastructure already in place was critical to our success and allowed the team to hit the ground running and become the study’s lead recruiters in Canada.”
The journey through Solidarity has been an enriching experience both professionally and personally for Cheng. “It’s interesting to note that the name Solidarity is not a fancy acronym, but rather a philosophy,” says Cheng. “We’re working together to find the best treatment for hospitalized patients with COVID-19 and, by partnering with others, can produce results that benefit not just Canadians but people around the world. This study demonstrates that we are truly stronger together than apart.”