|27th March 2020
Let's jump straight into the main topic of discussion without repeating any of the news you've already heard on promising COVID-19 treatments. This is not intended to add any extra 'noise', but to help us make sense of what's happening in terms of treatments to tackle COVID-19. Hopefully, by the end of this article most of you will feel there's a lot of promise in tackling the pandemic using pharmaceuticals.
Several questions arise when reading articles about the next big thing being investigated against COVID-19:
What is the rationale for this treatment? When will we know whether it works or not? When can we expect this treatment to become available? How promising is this treatment?
You may have read about a large number of drugs (ca. 60) currently or soon to be 'in-the-works' to tackle COVID-19. Some of the most comprehensive articles summarising these can be found here and to keep yourself continuously updated, I recommend this website. Here, we are taking a look at drugs that are already in registered clinical trials, which can be found in the largest clinical trials database, 'clinicaltrials.gov'.
Just a week ago, a search of 'COVID' in this database, yielded 50 clinical trials, whereas now the number of trials has jumped to 110. These trials are either observational or interventional. Examples of observational trials include a trial using AI to differentiate between influenza and COVID-19 patients based on chest X-rays, a trial comparing medical masks to N95 masks, and even a trial exploring the impact of COVID-19 on population's stress. Whilst there are a lot of interesting and useful trials like the above, let's instead focus on the interventional trials testing the efficacy and safety of different drugs.
Of the 95 trials, about half of these are interventional and after a close look, these trials could be largely broken into 3 categories: (1) prevention, (2) antiviral treatment and (3) disease/symptom management.
1. Prevention -
Soon after China made the COVID-19 genome sequence available to the public, on January 10th, researchers were able to design vaccines against the new virus. Although there are more than 10 vaccine candidates expected to initiate trials soon, three are currently already in trials, including Moderna's mRNA vaccine, which dosed its first healthy volunteer last week.
2. Antiviral Treatment -
Antiviral drugs administered shortly after symptom onset can reduce infectiousness by reducing viral shedding in the respiratory secretions of patients (viral load in sputum is known to peak at around 5–6 days after symptom onset and lasts up to 14 days), and targeted prophylactic treatment of contacts could reduce their risk of becoming infected. The table below contains a non-exhaustive list of some of the approaches explored currently in clinical trials:
3. Disease Management -
Part of how COVID-19 is able to cause a severe infection or even kill is that the virus overstimulates the immune system's inflammatory response. This is why approaches to modulate the immune system appear to have a place in the treatment of COVID-19. Below is a list of possible treatments, currently in trials. Many of these are marketed drugs, which means the safety profile of these drugs is well known, but we still need to see a benefit in COVID19 patients.
Use what, when?
Whilst it is still unclear how antiviral treatments and disease/symptom management approaches may best work, either alone or as combinations, research to understand this is currently ongoing. A group of researchers released a manuscript on a working hypothesis, suggesting which treatments could work at the different stages of the infection (figure below). The researchers propose a typical COVID-19 infection into three stages: Stage 1 (early infection), Stage 2 (pulmonary phase) and Stage 3 (hyper-inflammatory phase), each with separate clinical symptoms and signs (however, it should be noted that the clinical profile of COVID-19 is likely a lot more complicated than that, with many different presentations already observed in practice). Whilst antiviral treatments are suggested to be useful throughout the course of infection (to reduce contagiousness), there is a suggested timing in terms of disease/symptom management treatments, specifically, the "use of anti-inflammatory therapy applied too early may not be necessary and could even provoke viral replication such as in the case of corticosteroids".
The good news -
|27th August 2020
Precision and personalised medicines are more than products, they are services in their own right. So, how should pharma approach this uncharted territory to ensure targeted therapies work for patients?