Interview with Dr. Luciana Borio – Part 3

Dr. Luciana Borio (LB)
Randy Larsen (RL)
May 4, 2020

Part 3 – Therapeutics for COVID-19

RL  So one last topic for today … therapeutics … and I think that you will agree with me .. I’ve been telling people that we will have a therapeutic … maybe more than one effective and safe therapeutic long before we have a vaccine. Do you agree with that?

LB  I do. As of last week, we have an effective therapy for COVID-19, one that has been established to benefit patients with advanced (or serious) COVID-19. It is called Remdesivir, it is produced by Gilead, and it received an Emergency Use Authorization by the FDA. 

From the beginning of this pandemic, there have been a series of uninformative studies conducted with this and other drugs. I say uninformative because they were not randomized controlled clinical studies of adequate size. Instead, they were observational studies or did not enroll enough patients to detect a potential safety or efficacy signal. But the National Institutes of Health conducted a fairly rigorous study of over a thousand patients across 60 sites in the US, Europe and Asia. Last week they announced that Remdesivir was effective. Now, let’s remember that this drug is reserved for patients with advanced disease – it is intravenous … so it’s given in the veins and not by mouth. And is has some side effects. But it showed about a 30 percent reduction in the time it takes for symptoms to resolve, when compared to placebo. So instead of taking about 15 days to get better, patients who received it got better in 11 days. Some have said that it is not a silver bullet … and I would agree with that … but four days really matters for somebody with advanced disease.  And I am hopeful that as we move forward we’re going to have even better drugs … but this is progress.

RL  There has been a lot of controversy about using Hydroxychloroquine as a therapeutic for COVID-19. I realize it is a bit of a political hot potato, and there is no room for politics in patient care, but last month, I heard one of our colleagues, Dr Amesh Adalja, one of this country’s most respected infectious disease physicians, say he was using it on his patients, and that many of his infectious disease colleagues around the country were also using it. Care to comment?

LB   I, too, have tremendous respect for Dr Adjala. And I think the desire to offer patients hope may drive some decisions made at the bedside. What I can say is that there is absolutely no evidence that chloroquine or hydroxychloroquine have a role in the treatment of COVID-19. Its risks are well established, especially for this patient population. In the past, even when these drugs show activity in the lab, or even in animal models, against an emerging infectious disease, they have never worked (or proved to be harmful) when tested in patients. I really think we have to be careful not to harm patients by using these drugs outside of a randomized clinical trial, where safety and benefit can be monitored and measured. We owe it to our patients. In the NIH remdesivir study, the mortality of the patients with advanced disease who received supportive medical care only was about 12.8%. Those who say that we have little to lose by administering unproven treatments need to look at those numbers. I was very surprised to see the rapid uptake by the medical community, including highly respected academic institutions with a tradition of rigorous clinical sciences, of these unproved and potentially harmful treatments. Thankfully, I think most have moved away from that now. 

RL I have heard a lot of good news about monoclonal antibodies. Could these be a game changer?

LB  I think the next big advances are going to be the monoclonal antibodies that are being now prepared by amazing, amazing companies. They have relied on bioengineering to develop these treatments, and will likely going to be in the clinic around June. These monoclonal antibodies basically replicate the antibodies that the immune system develops in response to the infection. You can give it higher doses. They’re very active, very potent and they bind the virus. They can be used as a treatment or prophylactically. Some of them can be engineered to have a very long half-life, so they can stay in the bloodstream for months where they effectively act like a vaccine because they’re protecting individuals from infection. Now the downside is that, when compared to most vaccines, they are harder to manufacture in the quantities that are needed to replace a vaccine. Nevertheless, they could be really, really helpful to protect individuals who are very high health risk, such as our parents or grandparents who are in nursing homes … as we know that they’re very vulnerable to this infection. 

We still need to do the studies but I’m optimistic about those. 

RL  So it’s interesting you say that today it takes a long time to mass-produce them. That reminds me of the story about penicillin. Dr Fleming discovered it in 1928, but by 1941, no one had yet figured out how to mass produce it. A couple British scientists came to America seeking help. A consortium of American companies, including Merck, Squibb and Pfizer, began working on a solution. By the spring of 1944, 21 companies were working together, and by June 1944, just in time for the D-Day invasion, these companies had produced 2.3 million doses. It was truly a miracle drug that saved tens of thousands of soldiers from deadly infections.

So hopefully we can use that same kind of wartime effort today to produce these monoclonal antibodies. 

Do you have anything else you would like to add?

LB  Well I think it’s important to push the envelope, but do so in a way that is safe and not unduly risky. We must be mindful about moving forward with uncertainty. It’s a disease that we are still learning about, but we can’t wait to understand everything before we launch the clinical trials the way we normally do. 

This is a pandemic, so it’s okay to proceed with a certain level of uncertainty provided we manage the risk. To properly do that we need to evaluate these experimental products in  randomized control clinical trials. These types of trials are the most efficient way to ascertain whether a product is safe and effective. I think that gaining the trust of the American public is going to be critical and we only get to do that if we conduct proper clinical trials.