General May 2020
What are the odds of a Covid-19 vaccine anytime soon?
We are all pinning our hopes on a life-saving Covid-19 vaccine in the near future and there are tremendous efforts to bring this about, including in Australia. Just how likely is this, and what could Plan B (a non-vaccine solution) look like?
The New York Times a few days ago published an illuminating opinion piece by Stuart A. Thompson titled “How Long Will a Vaccine Really Take?”
The article sets out some sobering statistics and projections concerning the likelihood of an effective and safe vaccine within 12 – 18 months. This estimate is the rosy timeframe being projected by some governments and health officials. The article points out some assumptions and critical paths where this could be achieved – maybe – if everything went right. Thompson pointed out that we have never released a coronavirus vaccine before and our track record for development of a new vaccine is around 4 years, but these are unprecedented times.
The good news is that Governments and groups like the Bill and Melinda Gates Foundation have provided record funding to industry and academia to achieve this goal. At last count there are already at least 254 therapies and 95 vaccines related to Covid-19 being explored, and Phase 1 safety studies have begun.
What are the odds of obtaining a safe and effective vaccine quickly?
The statistics tell us that, in normal times, it takes on average 5-10 years to develop, and an additional year to license, a safe and effective vaccine and the success rate is low, at best 10 to 20% get to the market. The latter part is actually good news because if we have 95 vaccines on the drawing board, maybe we will end up with between 10 and 20 potential candidates.
It turns out we have a head start due to previous SARS/MERS episodes and the R&D undertaken. According to Thompson Coronavirus is around an 80% match to these other similarly spiked viruses. For example, Sanofi is anticipating clinical trials in late 2020 using a re-purposed SARS vaccine, with a possible approved vaccine within a year. Oxford University has also projected the possibility of a candidate vaccine around September 2020. In China Phase II studies, run in parallel with Phase 1 studies, have commenced in four trials. The USA now also has two clinical trials running at Phase 1.
Additionally, while it is true that a registered vaccine for coronavirus has not been approved, very encouraging Phase I data exists for a SARS vaccine developed in China. The elimination of SARS via isolation strategies meant that the vaccine could never be properly tested but these studies provide confidence that vaccines against coronaviruses are feasible and will likely provide a solution for COVID 19.
Furthermore collaboration between scientific institutes and companies across the globe, together with planned expedited regulatory processes, provides some confidence that a vaccine can be developed rapidly.
Assuming we get some good candidates in the next 12 months how will regulators evaluate? They certainly have the mechanisms to fast track evaluation and have done so in the past. Initial release is likely to be under emergency use provisions with restricted access to those most in need, with the general public gaining access at a later stage.
The next challenge – mass manufacture and distribution
The largest manufacturer of vaccines worldwide is Serum Institute in India who distribute around 1.6 billion doses per annum. If Serum Institute were successful and approved and all production was diverted to Coronavirus this may just cover Indian needs first and the rest of the world would wait.
Thompson in the NYT also pointed out the issue of manufacturing timelines and the need to purpose build and qualify vaccine production factories. Normally this can take up to 4 years from design to licensing but this could be speeded up to at best 2 years. In the meantime, existing vaccine facilities could be put into use.
Just to understand the enormity of this task and making some wild assumptions – if the goal was to produce 5 billion doses and a production line could manufacture 400 vials per minute, working 24/7 over a year it could take 24 years for any single factory to meet the need.
These are complicated, specialist facilities and we only have one in Australia. If we want the vaccine over a 2 year span this will require in excess of 12 factories working around the clock. This could also be ameliorated by multiple doses in a vial. While the above numbers are not realistic they do serve to highlight the massive task once a vaccine is licensed.
What to do in the meantime?
Recent emergency use approval of Gilead’s Remdisivir provides some hope, however the trial outcomes are a bit underwhelming and as the drug is only applicable when a patient is within late stages of lung inflammation, it does not sound like a solution.
While there has been recent unfounded suggestion of a “disinfectant” injection a somewhat kind interpretation of this statement may be that what Donald Trump really meant was a safe anti-viral agent that “cleans” out the virus.
Given the probability of a safe and effective vaccine appearing within the next 2 years perhaps attention should also be directed toward the 254 non vaccine solutions mentioned in the NYTimes article.
What would be an ideal non-vaccine candidate?
- One that was a preventive therapy that knocked out a good percentage of the virus so that its effects were not as severe;
- One that could be developed quickly, and this means one that has already undergone successful safety trials in humans for the dose form put forward and had a low risk patient track record say in Phase II or beyond trials;
- The candidate would also be stable at room temperature and easy to dose deliver, such as via intranasal mist, oral dose or transdermal patch;
- One that could be easily manufactured in large quantities and be widely available;
- Lastly it should also be within the financial reach of those who need it. (The Remdisivir prices are anticipated to be somewhere between USD$1000 – 4,500 per dose.)