In GlobalData’s Coronavirus Disease (Covid-19): Pipeline and Clinical Trial Analysis – April 2020 thematic report, 1,561 visitors of GlobalData’s Pharmaceutical Technology website responded to the question “How confident are you that Pharma/Biotech Companies will be able to develop an effective vaccine for Covid-19 within the next 12 months?” A strong majority (80%) were optimistic about the development of a vaccine, with 52% being very confident, 28% somewhat confident, and only 20% who expressed no confidence at all. However, considering that vaccines typically take years to develop, expectations surrounding the potential availability of a Covid-19 vaccine should be tempered.
Covid-19 therapeutics could be available within a matter of months, as off-the-shelf solutions may already be available and ready for clinical trials. Assuming rapid trial initiation, these trials could produce readouts in a matter of weeks. Data are already available for multiple candidate therapies, including chloroquine/hydroxychloroquine, ritonavir + lopinavir, remdesivir, and favipiravir, among others. Notably, these data have been produced less than five months after the discovery of the virus, demonstrating that short studies for Covid-19 treatments can indeed be completed quite rapidly, although the data are less clear than desired. However, it is unrealistic to expect vaccines to follow a similar timeframe for multiple reasons.
Vaccines work by training the immune system to respond to components of pathogens, and accordingly must be highly specific to the pathogen of interest. As the virus responsible for Covid-19 is new, its components are poorly understood, making it difficult to decide which parts might be more immunogenic and thus more likely to lead to a successful vaccine. While several vaccines have entered clinical trials, such as Moderna’s messenger ribonucleic acid (mRNA) vaccine mRNA-1273, the amount of time dedicated to the R&D of these candidates has been substantially shorter than other vaccines that have entered clinical trials. Part of the reason these vaccines were able to enter Phase I studies so quickly is because they rely on new vaccine technologies, such as DNA, mRNA, or adenoviral vector-driven vaccines, which can be developed rapidly relative to older technologies. However, no vaccine using these technologies has ever been commercialised, and data supporting their efficacy is thin. As such, enthusiasm surrounding their likelihood of success may be met with disappointment.
Prophylactic vaccines confer active immunity against a potentially disease-causing pathogen. Even if a vaccine is effective, the protection it confers must be measured against time because exposure to the pathogen could take weeks, months, or even years. This means that the endpoint for the time after immunisation needs to be longer rather than shorter in order to ensure that the pathogen is likely to have been encountered. If a trial is too short, an immunised patient might not be exposed to the disease, which could either make it difficult to differentiate the treatment from placebo or could confer a false sense of efficacy, as the rate of disease in the vaccinated group would be lower.
Even if a vaccine were to rapidly demonstrate efficacy in both Phase I and II trials, there would need to be significant manufacturing efforts initiated prior to proof of efficacy. Waiting for trial results could significantly delay the delivery of the vaccine to the public. However, increasing production prior to the release of the trial results is risky due to the possibility of failure to meet endpoints, so most developers usually avoid this option. The availability of a vaccine will likely depend heavily on the geography where it is developed and who is recommended to receive it upon licensure. For example, a Covid-19 vaccine developed in the US might initially be recommended for older patients in the US who are at increased of disease, while younger patients and those in other regions might have to wait for later releases of the vaccine.
While it is technically possible for a Covid-19 vaccine to be available in 12 months, there are multiple factors that suggest this to be closer to wishful thinking than anything remotely certain.
Figure 1: Industry Perspective on Vaccine Development. Credit: GlobalData