FirstWord hosted an expert call this week with Jason Kindrachuk – assistant professor and research chair in the department medical microbiology and infectious diseases at the University of Manitoba and associate professor of biochemistry at the University of Sierra Leone – to discuss the latest development status of various candidates being tested to treat COVID-19.
Summary points from expert feedback:
FirstWord: How optimistic are you that one or more therapies for treating COVID-19 will be successfully tested and approved in time to help head off the current outbreak?
“That is the million dollar question.”
“When looking at vaccines, I am not overly optimistic because of the amount of time needed to get it generated, tested in a suitable animal model and run some initial safety and efficacy studies. All those things suggest we are still 12 to 18 months away – and I am not confident this will go on that long. The pretty heavy increase in cases will likely go on well into the summer but I am hopeful we will have things under control and maybe back to normalcy by the fall.”
“I think there is more potential for other therapeutics. There are 80 or 90 randomised, controlled trials being run in China and hopefully we will be seeing data from some of them soon. There are some rumblings that some of the early findings look promising so maybe we will see something like remdesivir get at least emergency use authorisation (EUA) for at least severe patients.”
“I am not 100% confident but I am very hopeful that we have a good chance for a therapeutic.”
FirstWord: Is the bigger question whether a drug can be identified or, alternatively, whether a drug can be identified in time to be tested while the outbreak is still ongoing?
“Testing something in time is the question. I was at the National Institutes of Health for 7.5 years, including during the Middle East Respiratory Syndrome (MERS) coronavirus work when we were looking at repurposing drugs and in particular kinase inhibitors. We identified a lot of therapeutics with in vitro activity and some host-mediated antiviral activity.”
“Identifying candidates can be done rather quickly thanks to throughput screening but clinical testing takes time. At least with this pandemic we have a little bit of data from previous outbreaks. Remdesivir, for example, is being tested and there has been some talk about chloroquine and its potential efficacy.”
“Ebola was a learning experience. I was in West Africa, and have been back five times this year. I don’t want to say we have to take our opportunity when it presents [because that sounds callous] but we have gotten too accustomed to needing the perfect animal model and everything being tested to the nth degree before getting into patients. That works for infectious diseases that come around routinely but is difficult when something like this emerges, so we need to be ethical but be okay pushing things a bit in order to be responsive.”
FirstWord: Is it possible that there are too many asymptomatic people infected with the virus for therapeutics to be useful?
“Yes, the unfortunate thing with SARS-CoV-2 (the cause of COVID-19) is that 80% of patients affected have mild or potentially subclinical symptoms. That is a massive issue.”
“With Ebola, anyone who got infected has a really good chance of getting severe disease. Even mild disease is recognisable with Ebola. With COVID-19, we don’t necessarily have the same opportunity because most people don’t present symptoms. How do you assess the efficacy of a therapeutic if the population you are testing predominantly has mild disease? The best thing to do is look at overt symptoms. Fever seems to come with the virus and there is some mild cough but ultimately you have to do swabs to check the viral load, which is the best bet for understanding the effect in mild patients.”
FirstWord: Is there reason to think one of the modalities being worked on – such as small molecules, RNA interference or cell therapies – has a higher likelihood of success than others?
“I don’t think we know.”
“I look back at the Ebola experience. I am a virologist and what we learned is the situation is fluid. We thought Zmapp [from Mapp Biopharmaceuticals] looked fantastic and that it would be the front-line therapy then it got pulled out of clinical trials, which opened up my eyes.”
“There have been some therapeutics testing for other coronaviruses like severe acute respiratory syndrome (SARS) and MERS with varying degrees of success. Remdesivir seems to be the one that has the most focus right now. There is a lot of belief that it will potentially be a front-line therapeutic because the mechanism seems in line with what we would hope. There is some debate about whether combinations of HIV drugs like Kaletra [lopinavir/ritonavir from AbbVie] might have benefit. The evidence is not from randomised clinical trials but at least it is something.”
“We have seen that some repurposed drugs look promising. Remdesivir could have some positive effects based on what people are saying.”
FirstWord: How optimistic are you about the prospects for remdesivir when preliminary results from studies in China start becoming available in the near-term?
“I am pretty optimistic. The reason I say that is because there has been such a strong focus over the last five or even 10 years to move away from just looking at vaccine development and towards therapeutics targeting the pathogen directly and host-mediated response. There has been a lot more investigation of both in vitro and in vivo mechanisms to get a better sense of efficacy.”
“I am fairly optimistic. We are not just throwing the kitchen sink the problem. There is some data suggestive of a potential benefit. I have quite a bit of confidence.”
FirstWord: Would you say remdesivir has the highest likelihood of success among therapeutics in development?
“I think so. I haven’t been involved in the trials but the preliminary data coming out has looked good, plus there is some anecdotal evidence from individual patients, so I have some faith in it. Still too early to say anything for sure but we should find out pretty soon.”
FirstWord: How optimistic are you about the use of HIV drugs like Kaletra?
“When we look back at SARS and MERS there is at least some evidence that potentially there is an effect, though most of the suggestions have come out of Singapore or Thailand and we have yet to see the data.”
“I am a little hesitant because the majority of use has been in combinations that basically involve throwing things together, which makes me nervous because trying to separate out the components is tricky.”
FirstWord: In general do you have higher hopes for a repurposed agent (like remdesivir and/or Kaletra) or those taking an entirely novel approach?
“The adage says it takes 10 years and $1 billion to get from bench to bedside when trying to identify a novel therapeutic and I think it is really a shot in the dark, especially when starting in an academic lab where they are living grant to grant.”
“Repurposing fits our priorities better because you remove a layer of the development work, and you already have good information about mechanism of action and some pharmacokinetic data.”
FirstWord: Are you more or less optimistic that a drug will be successfully developed now versus when the virus first emerged a few months ago?
“I am more optimistic now. We saw initial cases on December 31 and a big talking point was whether there is appetite for developing therapeutics for coronavirus. Some of the interest died off when MERS did not go global, despite the fact it is still an issue that kills people in the Middle East.”
“This going global changes everything. The appetite is there because people are seeing what the virus can do in real time.”
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