COVID Drug Trials in and near The Bronx
What if you or I were to test positive for Covid-19; then what? We’d want our doctor to prescribe medicine, right? Certainly if we went to a hospital, we’d do so in the hope of receiving treatment. But there’s a problem. In the words of the Centers for Disease Control (CDC):
No FDA-approved drugs have demonstrated safety and efficacy in randomized controlled trials for patients with COVID-19. Use of investigational therapies for treatment of COVID-19 should ideally be done in the context of enrollment in randomized controlled trials. Several clinical trials are underway testing multiple drugs with in-vitro antiviral activity against SARS-CoV-2 and/or immunomodulatory effects that may have clinical benefit. [Ref: https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html]
The Infectious Disease Society of America elaborates:
Given that the panel could not make a determination whether the benefits outweigh harms for these treatments it would be ethical and prudent to enroll patients with COVID-19 in clinical trials, rather than use clinically unproven therapies. There are multiple ongoing trials, some with adaptive designs, which potentially can quickly answer pressing questions on efficacy and safety of drugs in the treatment of patients with COVID-19. [Ref: https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/]
What follows is not a substitute for discussing your best course of action with your doctor, but might serve as a guide for what questions to ask. Your motives could come into play. By participating in a clinical trial, you will be helping doctors develop drugs for those who come after you. You may also receive more tests, closer monitoring, and a lower or no hospital bill afterward. On the other hand, in the case of a double-blind placebo-controlled study, neither you nor the doctor treating you will know whether you are receiving a substitute for the medication being tested, or the real thing.
If you do not sign up for a study of an investigational drug, your doctor can still prescribe a drug approved for a different condition “off-label”. In the cases of choloriquine and hydroxychloriquine, the FDA has explicitly issued an “Emergency Use Authorization”. For any number of reasons, though, your doctor may be reluctant to take that step.
Before discussing the different types of medications under study as possible COVID-19 treatments, the arc of the disease should be understood. According to Massachusetts General Hospital’s Advances in Motion newsletter:
Several groups have measured respiratory SARS-CoV-2 RNA throughout the course of COVID-19. The viral load seems to peak during the asymptomatic phase or the phase of nonspecific symptoms, then decrease in the proinflammatory phase when acute respiratory distress syndrome (ARDS) can develop. There appears to be a correlation with higher peaks and worse clinical outcomes.
These observations have led to the hypotheses that the clinical manifestations of SARS-CoV-2 infection, in later stages, are related to dysregulated immune response, and dampening that response may prevent severe disease.
Drugs with antiviral activity interfere with a virus’ ability to replicate and spread. Assuming the description above is correct, it makes sense to start such a drug in the early stages of COVID-19, well before symptoms create a life threatening crisis.
Remdesivir and favipiravir are antivirals. When I asked Virology Prof. (em.) Dr. Erik De Clercq whether the two were of the same class of antivirals, he replied:
Both remdesivir and favipiravir are targeted at the same enzyme, RNA-dependent RNA polymerase (RdRp). To this end, remdesivir had to be stripped from its phosphoramidate moiety and subsequently phosphorylated intracellularly to its 5’-triphosphate. Favipiravir is a pyrazine analogue, which once taken up by the cells has to be converted to its 5’-monophosphoribosyl derivative and subsequently to its 5’-triphosphate.
Take that as a yes, but as a practical matter there is an important difference. Remdesivir is an injection (generally administered as an IV drip), while favipiravir is a pill. Given the arc of the disease described by Massachusetts General Hospital, the ability to start taking an antiviral as soon as the disease is diagnosed is probably an advantage. The only trials of favipiravir currently underway in the United States are in California and Massachusetts. A promising new antiviral pill, EIDD-2801, is not yet in human trials.
There are other types of drugs with antiviral activity. The anti-malarial drugs chloroquine and hydroxychloroquine are thought to interfere with the COVID-19 virus attaching to cells, which it must do in order to reproduce. But chloroquine and hydroxychloroquine are known to be hard on the heart, so if you have a heart condition, be particularly wary. Some think this treatment should be considered for those with diabetes, though, which is also a high-risk category. A paper from India published in the United States by the National Institutes of Health (NIH) states:
Because HCQ has been approved in the treatment of type 2 diabetes in India since 2014 as a third- or fourth-line drug, it would be interesting to research its impact in patients with diabetes, infected with COVID-19. It has been increasingly learnt that the anti-viral and anti-inflammatory activities of chloroquine may have a role in the treatment of patients with novel COVID-19. The only viral disease where chloroquine was modestly effective so far before COVID-19 era was chronic hepatitis C suggesting an increased virological response to pegylated interferon plus ribavirin.
So hydrochloroquine was not understood to be an antiviral previously, except as part of a 3-drug hepatitis C cocktail. The known side-effects include heart damage, but the drug is worth discussing with your doctor if you’re diabetic.
The site www.livescience.com, which has distinguished itself in this crisis, has been reporting on a question of interest to those with hypertension (high blood pressure). The COVID-19 virus attaches itself molecularly to a receptor involved in regulating blood pressure called ACE2. Blood-pressure medications interact with this receptor in various ways, and researchers are interested in whether any existing medication either blocks or promotes viral entry. Some researchers have speculated that Losartan might be more protective than others; studies are investigating at University of Kansas Medical Center and University of Minnesota. LiveScience health reporter Nicoletta Lanese expects information in the coming weeks.
All the above is prelude to the second part of the arc laid out by Massachusetts General Hospital’s Advances in Motion newsletter: acute respiratory distress syndrome. Inflammation is an immune response that under some circumstances can protect your vital organs, triggered by cytokines like interleukin-6. Just as your body can have an allergic reaction, however, it can overreact to COVID with what doctors refer to as a “cytokine storm”. That’s when the right anti-inflammatory can save your life.
Tocilizumab from Genentech is the best known of the interleukin-6 antagonist anti-inflammatories. Both it and sarilumab from Sanofi & Regeneron have been FDA approved for the treatment of rheumatoid arthritis. Because Regeneron is based here in New York State, the Regeneron studies of sarilumab’s use against COVID-19 symptoms are more plentiful in our area. These trials are being managed by Regeneron directly.
Something about the Regeneron study site location in the Parkchester / Westchester Square area strikes this reporter odd. It appears to be at neither Jacobi nor Montefiore, but at the Bronx Psychiatric Center. As of this writing my phone calls to Regeneron have not produced an explanation, but they answer their telephones and seem interested in speaking with COVID-19 patients ready to enroll in their studies, and their doctors.
You can find out more about any of the studies listed in this table by entering a number from the right-hand column at https://clinicaltrials.gov/, https://www.centerwatch.com/ or https://www.smartpatients.com/trials/.