AS the rollout of Covid vaccine passports begins in Scotland and Wales, and No Jab, No Job mandates for English care home workers come into effect, the question for governments, regulators and manufacturers is whether a new class of gene therapy pharmaceutical, the understanding of which is still evolving, has been evaluated against the wrong regulatory framework to give it an easier ride through the approval process.
As increasingly coercive measures are deployed to increase uptake of gene therapy vaccines which are now being administered to adolescents following the overruling of advice given by the Joint Committee on Vaccination and Immunisation (JCVI), are the jabs truly safe? Did the millions of healthy people who received them under a temporary use authorisation while the trials are ongoing, accepting them at face value as vaccines, give, as is their right, free and fully informed consent to becoming genetically modified humans? In the absence of such informed consent, has an ethical line been crossed where the administration of these injections to humans enters the realm of non-consensual experimentation?
For nearly 12 months Pfizer/BioNTech and Moderna mRNA vaccines, which the temporary use authorisation said were indicated for active immunisation to prevent Covid-19 infection, have been administered to millions. Yet it appears that a regulatory quirk made it possible for a revolutionary biomedical technology, never before licensed by regulators, to be authorised by a back door for widespread use in humans a meagre four months after the clinical trials were registered.
A pharmaceutical class now exists that can simultaneously be a gene therapy for one purpose, and not a gene therapy when deployed for another, a Schrödinger’s pharmaceutical if you will.
Provision 2.1 in the annex of EU Commission Directive 2009/120/ECstates: ‘Gene therapy medicinal products shall not include vaccines against infectious diseases’. As all lawyers know, to interpret such a provision correctly, the purpose behind it must be understood to avoid it being exploited improperly. The provision is ambiguous: it could arguably be read to exclude gene therapies from use against infectious diseases but has instead been read to deny that they are gene therapies at all when they purport to be vaccines.
The intention behind the provision and its recent application appear at odds with one another as nothing in EMA documents predating the 2009 directive suggests any awareness of the possibility that genetic technologies such as mRNA vaccines which genetically manipulate humans rather than the viruses that afflict us were in the contemplation of the directive drafters.
Pre-2009 EMA documents shed light on the origins of the anomaly. It existed to permit advances in gene manipulation techniques, which the documents acknowledge was a regulatory deep space at the time, to be used to enhance the development of conventional vaccines based on weakened (attenuated) viruses or viral vector vaccines. The AstraZeneca Covid-19 vaccine is an example of a viral vector vaccine that contains a genetically modified organism (GMO). Vaccines containing GMOs were intended to progress through the regulatory approval process in the ordinary way, a process that customarily takes a decade, enabling the identification of any long- or short-term safety issues prior to widespread use.
BioNTech advised its investors on April 22, 2020, shortly after the World Health Organisation announced that Covid-19 had become a pandemic, that it was commencing clinical trials for Covid-19 vaccines. It secured a €100million loan from the European Investment Bank in June 2020 and registered its clinical trial with the European Medicines Agency (EMA) in August 2020. Using the loophole, it did not acknowledge its Covid-19 drug candidate as an ‘advanced medicine’. It was not, therefore, evaluated as a gene therapy under the advanced medicines clinical trials protocols which are more onerous than the protocols for vaccines.
As stated in the December 2020 UK Medicines and Healthcare products Regulatory Agency (MHRA) Public Assessment Report for the authorisation of temporary supply of this gene therapy ‘vaccine’, amongst the studies not conducted during the trials were studies of pre-natal and post-natal development, including maternal function or studies in which the offspring are dosed and/or further evaluated. A previous BioNTech mRNA drug candidate trial registered with the MHRA in 2018, for a cancer drug utilising the same biotechnology, was by contrast, acknowledged to be an advanced medicine.
In an interview earlier this year with the Science History Institute, Stephane Bancel, chief executive officer of Moderna, the manufacturer of a competing mRNA vaccine, said: ‘So the idea of using messenger RNA back in 2011 was a bit of a crazy idea. We all believed in the field that messenger RNA could not be a safe drug because it was believed to be unstable, as a molecule. And was believed to be highly immunogenic, so giving you flu-like symptoms when you inject that molecule into a human body.’
A 2017 journal paper on the regulatory environment, whose co-authors include scientists from the German biotechnology firms CureVac and BioNTech, indicates that they had identified the anomaly which permitted a route to market for the gene therapy vaccines that later sent their profits soaring stratospherically. The scientists interpreted the provision thus:
‘In the EU no regulatory guidelines presently exist that specifically address mRNA-based vaccines. The existing regulatory framework, however, clearly defines that mRNA-based vaccines in most cases have to be centrally approved. Interestingly, depending on whether RNA-based vaccines are directed against tumours or infectious disease, they are formally considered gene therapy products or not, respectively.’
A temporary emergency derogation issued by the European Parliament in July 2020 as manufacturers scrambled to develop Covid-19 vaccines permitted the setting aside of some of the ‘time-consuming’ elements of clinical trials, including the requirement to conduct an environmental impact study prior to the release of genetically modified organisms. EU law was fully effective in the UK during the Brexit transition period.
In 2015, CureVac sold a $52million equity stake to the Bill & Melinda Gates Foundation (BMGF), agreeing to construct a new Good Manufacturing Process (GMP) facility to produce mRNA vaccines at industrial scale. The announcement described CureVac as ‘pioneering the use of natural and chemically unmodified mRNA as a data carrier to instruct the human body to produce its own proteins capable of fighting a wide range of diseases’.
The press release went on: ‘ “If we can teach the body to create its own natural defenses, we can revolutionize the way we treat and prevent diseases,” said Bill Gates. “Technologies like mRNA give us confidence to place big bets for the future. We are pleased to partner with CureVac who has been pioneering this technology”.’
When the 2017 paper was published, CureVac and BioNTech were developing advanced gene therapies for cancer treatment, which in ordinary times generate higher returns than vaccines. The commercial appeal of vaccines for infectious diseases is that they have an overall success rate in making it to market of 33 per cent, ten times higher than the 3 per cent success rate for cancer drugs. Neither company had yet succeeded in getting regulatory approval for their cancer therapies.
A 2007 EMA concept paper identified the need to develop regulatory guidelines for clinical trials and long-term monitoring of gene therapy and gene transfer medical products. However, once classed as vaccines, biotechnologies which were originally developed as advanced gene therapies for cancer bypassed any such guidelines that existed giving them an easier path through the regulatory approval process than would otherwise have been possible. The manufacturers’ hope is that authorisation for use against Covid-19 will reduce the regulatory hurdles for the authorisation of mRNA products against other diseases including cancer.
The manufacturers view mRNA technology as a ‘platform’. In the June 2021 Science History Institute interview Moderna CEO Stephane Bancel explained, ‘Because mRNA is an information molecule, if you could make it work once, it will work for a lot of things, a lot of medicine. And this could change medicine because you could make basically, uh, people make their own medicine by sending an instruction set. A piece of mRNA is an information molecule, it’s a piece of code. It just instructs a cell to make the protein you want.’
Moderna’s foray into infectious diseases began in 2015 when it partnered with Merck & Co, the pharmaceutical giant behind vaccines such as MMR and Salk’s polio vaccine, to form an infectious disease vaccine development subsidiary, Valvera. Merck, which held a 50 per cent equity stake in Valvera, invested $175million between 2015 and 2017. The venture also received a $20million grant from the BMGF.
On January 23, 2020, during the World Economic Forum (WEF) meeting in Davos, Moderna secured an agreement with the BMGF-funded Coalition for Epidemic Preparedness Innovation (CEPI) to develop a Covid-19 vaccine. The agreement was negotiated while a WHO delegation was making its preliminary visit to Wuhan, a city of 12million, after being notified by the Chinese Government on December 31, 2019, of their concerns over a small cluster of serious pneumonia cases. At the time the agreement between CEPI and Moderna was inked, there had been 17 deaths reported from COVID-19 in China.The WHO declared a Public Health Emergency of International Concern (PHEIC) under the 2005 International Health Regulations on January 30, 2020.
On December 2, 2020, after the MHRA granted a temporary use authorisation to Pfizer/BioNTech’s covid, Merck & Co announced it had divested from Moderna. No counterparty for the sale was identified, suggesting instead that the ‘material breach’ clause of their partnership agreement was activated. Merck’s CEO Ken Frazier had voiced concerns months earlier about the safety of such rapid development of the vaccines using new technologies.
Not only was the vaccine technology new, but all previous attempts to develop vaccines for coronaviruses had failed. In 2012, researchers working on a vaccine for SARS which had first appeared in 2003 reported on the outcome of their animal studies concluding: ‘Caution in proceeding to application of a SARS-CoV vaccine in humans is indicated.’
A disclosure in BioNTech’s October 2019 Securities Exchange Commission (SEC) initial filing document for BioNTech’s Nasdaq launch indicates that its infectious disease vaccine candidates were only at the pre-clinical trials phase at the time of filing and not expected to enter Phase 1 until the end of 2020. The filing also disclosed that BMGF had taken an equity stake in BioNTech.
On December 19, 2019, Bill Gates tweeted, ‘What’s next for our foundation? I’m particularly excited about what the next year could mean for one of the best buys in global health: vaccines’
Gates, the founder of CEPI, has championed mRNA products since he famously warned in his 2015 TEDTalk about the dangers of a pandemic of some infectious disease threatening the world. When CEPI was launched in 2017, Gates expressed his hopes for the new technology.
He said: ‘Now there’s a new class of vaccine, DNA / RNA vaccine, that we hope we can just change a small part of it, and so the manufacturing facility would already be there, the trials you would go through would be very quick. You would understand what end point, what correlate you want and so in an emergency, the regulators would understand what sort of protocol we’re going to use.’
CEPI is the brainchild of Gates and Dr Jeremy Farrar, the infectious disease specialist appointed director of the Wellcome Trust in 2013. Farrar came to public prominence in 2005 as part of a team that identified bird flu in Vietnam. Conceived at the January 2015 World Economic Forum in Davos, halfway through Gates’s ‘Decade of the Vaccine’, CEPI exists to find what it characterises as ‘just in time, just in case’ solutions to prevent epidemics of infectious diseases cutting a swathe through the world’s population.
The inspiration for CEPI came during the outbreak of the haemorrhagic fever Ebola in West Africa in 2014. While not easily transmissible, with an average mortality rate of 50 per cent Ebola has a unique capacity to frighten people. The World Health Organisation declared Ebola a Public Health Emergency of International Concern (its unfortunate acronym PHEIC is pronounced ‘fake’) in August 2014, but by January 2015, when a Wellcome Trust-funded viral vector vaccine was entering final stage trials, the outbreak was already fizzling out.
Gates applied his business acumen to vaccines, revolutionising them the way he had computer software. He said: ‘But the scientific idea of these new platforms could radically change that, so that a lot of the steps are sitting there ready, the factory piece, understanding the regulatory piece, and you just have to plug in some information, do some quick safety profiles and then you can get into manufacturing quite rapidly.’
The WHO upgraded the Covid-19 PHEIC to a pandemic on March 11, 2020, enabling vaccines to be deployed on an emergency use basis, provided that no treatment existed. Prime Minister Boris Johnson and his special adviser Dominic Cummings were lobbied.
Cummings later told a joint meeting of the Health and Social Care Committee and Science and Technology Committee: ‘The conventional wisdom was that we were not going to be able to have any vaccines in 2020. In March, I started getting calls from various people saying, “These new MRNA vaccines could well smash the conventional wisdom, and don’t necessarily stick to it.” People like Bill Gates and that kind of network were saying that.’ The two Gates network people he referred to by name during his testimony were Dr Farrar and the Oxford University Regis Professor of Medicine, Sir John Bell.
Bell, who is also chief scientific officer of BMGF, told a Parliamentary hearing in 2020: ‘The development of vaccines is a world that historically has gone very slowly. It normally takes years and years and years. To the credit of Sarah’s [Professor Dame Sarah Gilbert] group and the Jenner [Institute, Oxford], they have really changed the way people think about the speed at which these vaccine trials can be done. We all remember when Tony Fauci, who was brought in to help the Americans with their vaccine efforts, said in April, “Oh, don’t expect anything till mid‐2021.” The reality is that the way Sarah and Andy Pollard, who is helping to run the clinical trials in Oxford, have approached this has rewritten the book on how quickly you can do vaccine studies. We now find that many of the other big commercial players are trying to mimic the Oxford approach, and I think that is a great credit to the UK in terms of setting the style in which you can get these things done, but retaining very close attention to the safety issues, which is obviously the thing that we need to pay attention to.’
Cummings was an ideologically aligned helpmate. ‘You have to take risks, and when we looked at the EU plan, not just me but all the people that really understood vaccines and some procurement experts that we asked to look at it all said, “The EU plan looks like the classic EU Brussels thing. It will be completely bogged down in bureaucracy. They will not be able to take the right financing decisions. They will not do this parallelism approach of building everything and subsidising everything as you go along”.’
Referring to the May 2020 creation of the UK Vaccine Taskforce led by Kate Bingham, Cummings recalled, ‘We said to her “Treat this like a wartime thing. Ignore rules. If lawyers get in your way, come to us and we’ll find ways of bulldozing them out of your way”.’
Perhaps now we know what he meant. When lawyers are involved, the meaning of words, intention and purpose are all in play. It appears lawyers have been lawyering.
In June 2020 Bingham told the Commons Science and Technology Committee that the UK regulator the (MHRA) was embedded within the taskforce to facilitate the process: ‘We are absolutely compressing the clinical trial process, which is why we have MHRA embedded with us . . . MHRA is universally known to be an incredibly flexible and thoughtful regulator. We hear very good comments from the different companies we talk to around the world; they now preferentially want to come to the UK because they know that the MHRA is willing to talk to them at a very early stage, and look at the data and the documents before they have even got beyond a draft stage, so that they can give input along the way and therefore be able to turn it around quickly.’
On November 4, 2020, when Bingham updated the Parliamentary Science and Technology Committee on the progress of the two most advanced candidates, the AstraZeneca and BioNTech vaccines, she said, ‘They are very different vaccines, but they are both in a position where we should be able to look at the interim data this year, or at least the first set of interim data.’
The following month Margaret Keenan became the first recipient of the Pfizer/BioNTech vaccine under the temporary use authorisation. The vaccine roll out was barely 100 days old when CEPI, the Coalition for Epidemic Preparedness Innovations, which has funded many of the Covid vaccines, announced its Moonshot target further to reduce the approval time for new mRNA vaccines to 100 days.