LONDON – The first 800,000 commercial doses of Pfizer Inc./Biontech SE’s COVID-19 vaccine are due to arrive in the U.K. over the next few days, after the Medicines and Healthcare products Agency (MHRA) became the first regulator to grant conditional approval.
A total of 1,500 immunization centers in the U.K. are preparing to receive the vaccine, with administration now expected to start on Monday, Dec. 7.
The vaccine, BNT-162b2, becomes the first messenger RNA (mRNA) drug to be approved, leapfrogging the multiple programs in which mRNA is being developed as the basis of cancer vaccines.
It has been a remarkably swift development, with the product progressing from a standing start when the SARS-CoV-2 genetic sequence was made public on Jan. 12, 2020, to the point where alongside the MHRA, both the FDA and EMA are poised to give emergency approval this month. Pfizer and Biontech said they will deliver 500 million doses before the end of 2020 and 1.3 billion doses in 2021.
Chinese and Russian regulators have both approved COVID-19 vaccines, but that has been on the basis of phase II data.
The U.K has a contract for 40 million doses in 2020-2021, the EU for 200 million doses with an option for a further 100 million, and the U.S. has a contract for 100 million doses, for which it will pay $1.95 billion, with an option for a further 500 million doses. Pfizer said that pending approvals, the vaccine will be distributed pro rata, on the basis on population size.
The MHRA’s decision is based on a rolling submission, including data from the phase III, in which BNT-162b2 was 95% effective in preventing people from contracting the infection from seven days post the second injection. All the agencies have seen the same data, and have been assessing the different packages over several months. The fact that the MHRA is first to grant an approval is down “to differences in the underlying processes” rather than different standards in scrutinizing the data, said Ben Osbourn, Pfizer U.K. managing director.
“The rest of the world is looking at the U.K. and [at] accelerating approval,” said Rene Reinert, professor of microbiology and infectious diseases, who is vice president for Medical and Scientific Affairs at Pfizer Vaccines. “When you sent an email to MHRA you got a reply in 10 minutes; you were quick in responding,” Reinert, who is based in Frankfurt, Germany, told attendees of a U.K. press briefing.
The FDA review is on Dec. 10, while the EMA has said its scientific committee for human medicines will conclude its assessment during an extraordinary meeting scheduled for Dec. 29 at the latest. The European Commission will then fast track its decision-making process with a view to granting a conditional marketing authorization, valid in all EU member states, within days.
With the U.K. still operating under the EMA regulatory framework until the end of the Brexit transition period on Dec. 31, the MHRA made its assessment under regulation 174, an EU rule that allows national decisions to be made in public health emergencies. Other EU countries could have chosen that route but decided to stick to the EMA centralized authorization procedure.
Accusations are flying that the MHRA has put speed before ensuring there is public confidence in COVID-19 vaccines, but June Raine, head of the MHRA said that “no corners have been cut.” The MHRA’s recommendations, “followed an extremely thorough and scientifically rigorous review,” she said.
“We of course plan to have full licensure and approval in due course,” said Özlem Türeci, chief medical officer and co-founder of Biontech. “We’ve had a very positive experience with all regulators around the world. I wouldn’t see it as why MHRA was faster, but how fast the regulators were in general. They have all been highly committed and engaged.”
Properties of mRNA play out
Reinart said the expected benefits of mRNA have played out in the development of BNT-162b2, noting the safety benefits of not needing an attenuated virus, a viral vector or an adjuvant. In addition, the fact that no viral vector is used removes the risk of an anti-vector neutralizing immune response, thereby permitting repeated booster doses. And without the need for mammalian cell culture, production of the lipid nanoparticle encapsulated vaccine is fast.
Under a plan published by the U.K’s Joint Committee on Vaccination and Immunization (JCVI) on Dec. 2, the vaccine will first be administered to care home residents and staff, before being made available to front-line health care workers and people older than 80.
With BNT-162b2 requiring storage at minus 70 to minus 80 degrees centigrade, questions have been raised about the practicalities of that. However, Osbourn said although shipped at ultralow temperatures in “thermal shippers” containing 5,000 doses each, the vaccine can be stored in a normal fridge for five days, and is administered in the same way as any other vaccine. “That gives the flexibility to reach the target population identified by JVCI,” he said.
Pfizer briefed JVCI and other U.K. vaccines experts on stability and cold chain requirements last weekend, before the committee drew up its recommendations.
In the phase III trial, conducted at 150 sites in six countries, two injections of BNT-162b2 were administered 21 days apart to almost 44,000 volunteers, including people as young as 12 and people with diabetes, HIV, and hepatitis B and C infections. Forty-two percent of participants were from diverse ethnic backgrounds and 40.9% were ages 56 to 85.
The trial began on July 27 and had enrolled 43,661 people, of whom 41,135 had received the second dose, at the cutoff point on Nov. 13. The latest analysis showed there were 170 confirmed cases of COVID-19, of which 162 were in the placebo arm.
“There were 10 serious disease cases, nine of them in the placebo group and only one in the vaccinated group, so the vaccine also protects against serious disease,” said Ugur Sahin, co-founder and CEO of Mainz, Germany-based Biontech.
The trial population will be followed up for two years for safety and to assess the durability of response. “[BNT-162b2] induces a memory immune response, so the immune response could stay for months, maybe even years,” Sahin said.
At present, it is not known if being vaccinated prevents people from passing the infection on to others, but research to assess that should complete in the next three to six months.
The phase III study is now being written up for submission to a peer review journal.