Thursday, November 26, 2020

COVID-19 vaccine still some way off

There are now at least 5 vaccines which are being prepared for approval and rollout to the general population. But despite the vaccine candidates showing strong efficaciousness in phase 3 trials it is only the beginning of the end. It will be many months before a vaccine is approved and a widespread vaccination program begins.  

The top five vaccine candidates

In the game are Pfizer/BioNTech's vaccine codenamed BNT162, Moderna's vaccine mRNA-1273, AstraZeneca's AZD1222 and the Russian made Sputnik V developed at the Gamaleya Research Institute. There are also at least three Chinese developed vaccines, though only one has been approved thus far and only for military personnel.

For the West and much of the world, the main focus has been on the vaccines produced by Pfizer, Moderna and AstraZeneca.

The news of a breakthrough with the Pfizer/BioNTech vaccine on the 9th November brought a collective sigh of relief around the world as it seemed there was finally a glimmer of hope to finally consign the global pandemic to history. With efficacy levels of over 90% BNT162b2 certainly seemed to offer hope. The only major flaw seemed to be the fact that the vaccine needed to be stored and transported at ultracold temperatures below −70 °C, something would make distribution difficult and challenging at the very least.

Within a week Moderna announced it had also completed phase 3 trials which showed its vaccine mRNA-1273 had 95% efficacy. It also had an advantage that it could be stored at the temperature of a standard medical refrigerator of 2–8 °C for up to 30 days or −20 °C for up to 4 months.

The biggest game changer was the news that emerged on Monday 25th November when details were released concerning AstraZeneca's vaccine AZD1222.

Oxford University/ AstraZeneca announced their coronavirus vaccine's successful trial, preventing 70% of people developing symptoms with a higher efficacy of 90% by tweaking the dose. The vaccine also benefited from being able to be stored at temperatures of a standard medical refrigerator of 2–8 °C.

Costs and availability

Aside from the logistics and efficacy there is the subject of cost. The Sputnik V vaccine is reported to be rolled out with a cost of around $10 (£7.50). Meanwhile the Pfizer/BioNTech mRNA vaccine and Moderna mRNA vaccine are set to cost in the region of $20.00 (£15.00). However the Financial Times this week reported that Moderna could charge as much as $37 (£27.75) down from the earlier reported $50-60 (£37-45) price tag for the required double shot.

In this context the AstraZeneca vaccine has a further advantage in that it is being pitched at around $3-4 (£2.25-3.00). Part of the reason for AstraZeneca's low price point is their commitment at selling their vaccine 'at cost' during the pandemic.

Of course with the millions of doses required, and the infrastructure needed to immunise entire populations, government budgets will still be hard hit.

Approval process

The biggest issue facing the world, now that there are vaccines which have completed phase 3 trials, is the wait for the approval process to be completed.

In normal times the approval and rubber stamping a new drug or vaccine takes years with some agencies slower than others to process submissions.

The UK faces a more nuanced issue given the political decision to leave the EU. Across the EU all drugs, vaccines and medicines are approved by the European Medicines Agency [EMA]. 

Prior to the end of the Transition Period ending on 31st December 2020 the EU's approval by the EMA would be required. But after the 1st January 2020 any vaccine would require approval by the Medicines and Healthcare products Regulatory Agency [MHRA].

The MHRA is the UK's answer to the EMA or FDA in the US.

However, the MHRA is slow in approving new vaccines. The MenB (Meningitis B vaccine), took nearly 20 years from the first idea to the vaccine being licensed for use. In October the UK government sought to speed up the process [Guardian]. But delays could still slow the process of approval and rolling out of a COVID-19 vaccine.

Even the EU's EMA could take weeks to approve a vaccine despite also undertaking an ongoing oversight of the development of vaccine candidates [MarketWatch].

In the US the FDA has announced that its vaccine advisory committee will meet on 10th December. The committee will assess the companies' data and decide whether the vaccines are safe and effective enough for restricted use [Nature].

Some companies have already put forward their vaccine for approval, most notably Pfizer which is seeking approval for 'emergency use' [Politico]. But even with fast tracking, approval could still take some time [CNN].

What might concern some, is not just efficacy but also the safety of any new vaccine that gets approval [Guardian].

Safety concerns

While phase 3 trials are intended to determine what side effects a potential vaccine might have, due to the relatively small size of the numbers taking part in such trials, very small percentages of individuals affected by adverse effects often don't show up until rolled out on a mass scale.

The swine flu vaccine, Pandemrix, made by GlaxoSmithKline, is a case in point. It was given to 6 million people in Britain during the 2009-10 swine flu pandemic but was withdrawn after doctors noticed a sharp rise in narcolepsy among those who received it [Guardian].

The regulator said because the sleep disorder was so rare in people vaccinated – approximately 100 are believed to have been affected in the UK – it could not have been detected in any clinical trial.

This may all be moot after doubts were raised over AstraZeneca's vaccine data. While AstraZenica say their trials were conducted under the highest standards. But on Thursday 26th November the Financial Times called this into question.

Geoffrey Porges, an analyst at SVB Leerink [a specialist investment bank focusing on the healthcare sector, headquartered in Boston], said he thought it was unlikely the AstraZeneca jab would get approval in the US after the company "tried to embellish their results" by highlighting higher efficacy in a "relatively small subset of subjects in the study".

Anti-vaxxers, conspiracies and disinformation

The biggest threat comes not from the risks that a vaccine in itself might pose, but from the concerns of individuals in society which could be overblown and dissuade many from getting vaccinated.

False information relation to the MMR jab resulted in many parents not getting their children inoculated. The fear that there was a link between the MMR jab and autism was unfounded, but the failure by many not to have their children immunised resulted in a surge of measles cases over the coming years.

Already on Twitter and other social networks there are concerns raised. Many cite science fiction plots such as I Am Legend https://en.wikipedia.org/wiki/I_Am_Legend_(film) where a vaccine originally created to cure cancer wipes out most of mankind.

There are others that will refuse a vaccine merely on the fact that they believe the whole COVID-19 coronavirus pandemic to be a hoax.

Whatever the motivation, a number of surveys do appear to show a strong level of distrust or skepticism. One such survey conducted by Euronews in October showed just 37% of French people questioned would take a low-cost vaccine if it came available in the next year. This despite France being among the worst-hit countries in Europe from the disease, with more than 33,000 deaths as of the 16th October.

This compares starkly to several of France's neighbours, where a majority say they would get vaccinated. Respondents in the United Kingdom were keenest, with 63% backing vaccination, followed by Germany at 57% and Italy at 55%. Another poll seemed to indicate that globally around 75% of the population would take a vaccine. Asian countries seemed to show the most trust in a vaccine with 97% of people in China saying they would take a vaccine as soon as it became available. But the further West one goes vaccine skepticism grows with safety cited as people's biggest concern.

New waves ahead of vaccine

In the meantime there are far more pressing matters to deal with, that of keeping the virus under control until a vaccine is distributed. With Thanksgiving and Christmas on the horizon it will likely be impossible to prevent further spread as rules are relaxed [Guardian].

Britain, the US and parts of Europe are likely to be hit by a third wave in the new year. Meanwhile the UK will take a further hit economically, not only due to the coronavirus but also due to a likely no-deal Brexit which could hit Britain harder than the pandemic according to the governor of the Bank of England [Guardian].

Add to that the longer wait that Britain might endure whilst the MHRA ponders the approval of a vaccine whilst other countries are already vaccinating their populations. There could be a very real situation where Britain misses the boat as the EU's EMA approves a vaccine just days after the transition period ends. This would leave Britain having to lean on the MHRA to approve the very same vaccine before it could be rolled out.

Even with the vaccine, which will of course be welcome, a new battle will begin to save battered economies some of which have been harder hit than others. 

Lessons not learned

All of this was avoidable. Countries and regions that acted in January - e.g. China [4,634 deaths*], Taiwan [7 deaths], Singapore [28 deaths], South Korea [515 deaths], New Zealand [25 deaths] - and imposed strict rules concerning masks, lockdowns, testing and imposing travel bans, are now seeing their economies thriving. Furthermore many had only had a handful of deaths and cases in the hundreds. Hindsight is a wonderful thing, but it was exceptionalism that affected the way some counties failed to act rather than not knowing the threat . 

Taiwan acted within days of the first reported case of a strange pneumonia in Wuhan on 31st December and still has only 7 deaths [Wikipedia]. And many other Asian countries followed suit in the days and weeks to come. It wasn't until eleven weeks after the first case in China that Britain locked down. It wasn't just Britain, however. Many European countries were slow to react as was the US. And despite claims that governments have been following the science there have been different approaches in different countries concerning masks, social distancing and even whether testing of people was important [tvnewswatch]. 
 
But while there is a light at the end of the tunnel and a vaccine is on the horizon there is a danger that many countries are relaxing too soon and failing to learn by the mistakes they have made thus far.

tvnewswatch, London, UK

* While China's figures concerning the numbers of cases and deaths in the country are disputed, lockdown and quarantine measures do appear to have largely eradicated or controlled the virus with much of the country now returning to normality.

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