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 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.

Tuesday, November 24, 2020

Repeating past mistakes as COVID-19 cases rise

In  a little over a week Britain is about to relax Britain's month long lockdown and relaxes rules for Christmas gatherings. And in the US millions are preparing to celebrate Thanksgiving with Christmas also on the horizon.

But medical experts both sides of the pond have warned that Thanksgiving and Christmas gatherings could come with a risk [Guardian]. As COVID-19 cases rise US and UK in danger of repeating past mistakes.

Growing numbers

In the US 3 million passed through airports in the US over the weekend ignoring CDC advice not to travel as COVID-19 cases rose exponentially.

In fact some 3 million people were found to have contracted COVID-19 in November thus far, the worst month of the pandemic in the US.

Meanwhile deaths have also risen to more than 257 thousand people across the United States.

The numbers in the UK have also risen significantly with deaths varying from between 300 to 500 daily. In the US the daily numbers of those dying have averaged at about 1000 a day over the past few weeks.

The numbers seen in Britain are more worrying given the size of the population. The UK population is about a sixth that of the US and yet the weekly death toll is near to a half that seen across the United States.

Relaxing before Christmas

No-one can deny that for many people Thanksgiving in the US and Christmas in both the US and Britain are important festive occasions. But the mixing of people during a pandemic could well bring disaster.

In a televised address to the nation Boris Johnson, the UK prime minister, quipped that this was "the season to be jolly careful."

And yet on the 4th December shops will reopen, and while some areas will remain under tough restrictions, pubs and restaurants will also start serving once again. And in the lead up to the festive period it is likely the mix of alcohol and festive spirit could see a dramatic increase of COVID-19 cases.

Positive news

The UK PM's announcement came on the day of positive news from AstraZeneca as it announced that its vaccine could be a game changer as trials showed efficacy of some 90% in those that received two doses over two weeks.

But the news has to be tempered by the fact that it will take some time to manufacture millions of doses and for governments to put a mass vaccination program in place.

Repeating past mistakes

It is certainly true that major advances have been made since the 1918 pandemic especially concerning vaccines. But it appears that society has failed to learn the lessons of controlling the spread of the virus [USA Today].

On 28th November 1918 the Omaha World Herald ran a notice asking that people limit their Thanksgiving festivities.

However, despite over 200,000 deaths since March 1918, as Thanksgiving rolled around, some cities celebrated the relaxation of flu-related restrictions – partly due to opposition campaigns by retailers, theatre owners, unions, mass transportation companies and other economically stressed stakeholders.

The relaxation of rules brought more cases and more deaths. On 27th November, the day before Thanksgiving, St. Louis reported its highest new daily case count since the epidemic began, and Buffalo, New York, reported its largest jump in daily cases since the lifting of its pandemic ban weeks earlier.

While some towns and cities began to reintroduce curbs and restrictions, it all proved too late. On Dec. 6, the St. Paul Daily News announced that more than 40 Minneapolis schools were closed because of the flu, below the headline "SANTA CLAUS IS DOWN WITH THE FLU."

By January, the USA was fully engulfed in its third wave of influenza. The virus spread throughout the winter and spring, killing thousands more. It infected one-third of the world's population and killed approximately 675,000 Americans before subsiding in the summer of 1919 [CDC].

There is a popular aphorism which states, "Those who cannot remember the past are condemned to repeat it". The history books of the future will likely look back on how the US and Britain in particular failed to heed the warning of the past and unnecessarily added to the misery of the COVID-19 pandemic in the West. And all for the sake of a few days partying.

tvnewswatch, London, UK

Tuesday, November 17, 2020

Could a no-deal Brexit affect COVID-19 vaccine imports?

With just 45 days until Britain leaves the EU, there are fears that a deal may not be struck and that this could seriously impact the UK's ability to secure, ship in and distribute a COVID-19 vaccine.

Such a scenario might be considered scaremongering, but there are many warnings from ports, customs and experts that suggest a no-deal Brexit could affect the import and export of all goods to and from the UK as companies and the ports themselves are ill prepared [Guardian].

Hope of a vaccine

Last week markets were lifted by the hope of a COVID-19 vaccine on the horizon. On the 9th November Pfizer BioNTech vaccine released data which showed it had developed a vaccine with some 90% efficacy [Pfizer / BBC]. Global stocks soared and headlines speculated that life could soon return to normal. But the euphoria soon subsided after details emerged that the new Pfizer BioNTech vaccine had to be stored in very specific conditions, specifically that it had to be stored at -80°C.

However, within hours of the announcement of the breakthrough the UK Health Secretary Matt Hancock said the NHS and GPs should prepare from December to roll out the new coronavirus vaccine if it gets approved [BBC].

This week Moderna, another US drug company, announced it had also developed a vaccine with 94.5% efficacy. The Moderna vaccine also had the advantage that it could be stored in a normal refrigerator and could even remain stable for short periods of time at room temperature [Guardian].

On the face of it breakthroughs in the development of a COVID-19 vaccine are indeed positive news. Indeed, Dr Tal Zaks, Moderna's Chief Medical Officer, described the latest breakthrough as "the greatest moment of my life."

But there are a great many hurdles ahead. Despite the positive headlines, the news has to be tempered by stark realities.

The first major hurdle is production. Pfizer has said it should be able to produce up to 1 billion doses by the end of 2021. "Based on current projections we expect to produce globally up to 50 million vaccine doses in 2020 and up to 1.3 billion doses in 2021," the company said. Meanwhile Moderna said in September that it was on track to produce 20 million doses of its experimental coronavirus vaccine by the end of the year, though given the positive news this week it is likely to up production.

Even so, even at full capacity, neither company is likely to provide the numbers of doses needed to help restore a sense of normalcy.

The US population exceeds 330 million people and with current estimates only Pfizer could potentially roll out enough doses for the entire population before it could offer the product to other countries. To further emphasise the issue the US government has stated that it has purchased at least the first 100,000 doses [HHS].

Of course there are other vaccines being researched, at least 50 though only 10 have entered phase 3 trials. But even if the companies researching these vaccines make breakthroughs in the coming weeks or months they will face an uphill struggle to catch-up Moderna and Pfizer BioNTech in terms of rolling out production of doses [RAPS-COVID-19 vaccine tracker].

Securing a vaccine 

Moreover, the big hurdle for some countries will be securing and purchasing the vaccine.

The EU has already made deals with Moderna having been in talks with the company for its experimental COVID-19 vaccine at least since July, an internal EU document seen by Reuters showed.

On 24th Aug the EU Commission, which conducts talks with vaccine makers on behalf of EU states, said exploratory talks with Moderna had been concluded with the aim of signing a contract for the supply of 80 million doses of its vaccine, with the option of buying another 80 million [Reuters]. And on 16th November it emerged that the EU had also established plans to authorise a deal with German biotech firm CureVac, which is still in phase 2 trials, to secure up to 405 million doses of its potential COVID-19 vaccine [Reuters]. Both deals would easily enable, if properly distributed, allow the EU to vaccinate the entire block.

Earlier this year the UK government rejected the chance to join the EU's COVID-19 vaccine scheme [Euronews]. Thus Great Britain will have to make its own plans. In this regard the UK has agreed to purchase vaccines from several companies including 90 million doses from Janssen [BBC / UK Govt], and has reportedly ordered 30 million doses of  the Pfizer vaccine and hopes to receive 10 million doses by the end of the year [Mirror].

The UK has also reportedly signed a deal to purchase some 190 million doses of another, as yet unapproved, vaccine VLA2001 from the French pharmaceutical company Valneva [Pharmaphorum / Valneva]. 

Aside from the potential challenges faced by the UK concerning securing the right vaccines and its distribution, there have been questions as to whether Britain's leaving the EU could affect the import of the vaccine.

Brexit "won't delay supplies", govt claims

Grant Shapps, the UK Transport Secretary has insisted that Brexit will not cause disruption to the import of a vital coronavirus vaccine into the UK should talks with the EU conclude in a no deal scenario, and the Health Secretary Matt Hancock has also said he is "confident" a no-deal Brexit won't delay supplies, amid concern the Pfizer vaccine could be affected by Britain's EU departure.

However, only a week before the announcement concerning the Moderna vaccine, the National Audit Office warned that the government had not done enough to get the UK's borders ready for leaving the single market and customs union and that there would be disruption whether or not a trade deal was signed [Independent]. 

No-deal risks

Last year as a potential no-deal Brexit loomed in October some experts warned that some disruption was inevitable. "Despite intensive preparation by industry for every scenario, a no-deal Brexit risks disruption to the supply of medicines" throughout the EU, Andy Powrie-Smith, an official at the European Federation of Pharmaceutical Industries and Associations, told Reuters.

The warnings were echoed by the Guild of Healthcare Pharmacists who said that leaving the EU without a deal would bring a "significant risk" of disruption to the supply of medicines and medical devices [Pharmaceutical journal].

With less than 45 days to secure and ratify a deal with the EU many fear that a no-deal Brexit is more likely than ever.

And with ports warning that such a scenario will cause unprecedented chaos, even if vaccines are fast tracked the physical problems shipments might encounter on the road could hold up supplies [Sky News].

Whilst it may be the case that a vaccine may not be available well into 2021 due to the approval process required, the issues surrounding the importing of medicines and particularly much needed COVID-19 vaccines might well be impacted negatively by a no-deal Brexit.

tvnewswatch, London, UK