Progress on Covid-19 vaccines
And then there was one.
On Tuesday, pharmaceutical giant Pfizer announced that its two-dose mRNA vaccine against SARS-CoV-2 had achieved an efficacy rate of 90 per cent in an interim analysis of 94 cases from its final-phase clinical study. This was a world first and a huge breakthrough in the containment of coronavirus.
Australian officials, under the oversight of Health Minister Greg Hunt, immediately secured 10 million doses of the candidate vaccine from Pfizer and its German partner BioNTech.
“This is a victory for innovation, science and a global collaborative effort,” BioNTech’s co-founder and chief executive, Professor Uğur Şahin, said in a statement on Tuesday. “When we embarked on this journey 10 months ago this is what we aspired to achieve.”
The company, which owns a proprietary mRNA vaccine model initially designed to develop rapid-turnaround influenza shots, was one of the first out of the blocks when the novel coronavirus left Wuhan, China, in mid-January.
Project Lightspeed, as Pfizer called the initiative, lived up to its name.
Greg Hunt told reporters on Wednesday that the Pfizer–BioNTech candidate vaccine is one of just two that has been given a “provisional determination” by the Therapeutic Goods Administration, which allows it to be fast-tracked. The other is being developed by Oxford University and AstraZeneca, and was previously considered the global frontrunner.
While these two vaccines are on the fast track, Australia has so far purchased 134.8 million doses of four vaccines, including 40 million shots of a Novavax drug and 51 million units of another developed by University of Queensland researchers and the Australian company CSL.
As Hunt says, it is likely we will need all four in what has become a $3.2 billion gambit to help the nation past the worst pandemic since the Spanish flu.
“So we have enough not just for the Australian population, but for the Australian population three times over,” Hunt said on Wednesday. “… In terms of investment, there are few investments that any Australian government has ever made with a higher return on investment.”
Each potential vaccine – none has yet cleared the final hurdles that would allow it to be administered – will likely serve a different purpose. Some, for instance, are more effective in vulnerable populations such as the elderly or people with suppressed immune systems.
Similarly, each has its challenges.
For example, CSL can manufacture two types of vaccine and that process will begin this week with work on the AstraZeneca drug. Australia does not, however, currently have the ability to manufacture mRNA vaccines such as Pfizer’s drug.
“There has never been an mRNA vaccine,” Hunt said on Wednesday. “[It] has never been produced anywhere in the world.”
Messenger RNA vaccines are the newcomers in global health. They represent an exciting development because they can theoretically be repurposed for new types of pathogens with relative ease.
The concept is simple.
Scientists produce a synthetic copy of the messenger RNA (mRNA) of the virus – essentially the instruction pamphlet for assembly – and inject it into the human body. In the case of the Pfizer candidate, the mRNA strand is the code for the full-length “spike protein” of the coronavirus. Because there have been so many other coronaviruses, researchers know it is this spike protein, which gives the virus particle its distinctive crown-of-thorns surface covering, that triggers the body’s immune defences.
An advantage of mRNA over other vaccine types, such as those that use small or inactivated doses of the pathogen or its key proteins, is that it produces an immunity that is potentially stronger and with possibly fewer risks.
“Unlike live attenuated vaccines,” Pfizer says in its trial protocol, “RNA vaccines do not carry the risks associated with infection and may be given to people who cannot be administered live virus, for example pregnant women and immunocompromised persons.”
While manufacturing for these vaccines is new, the process is also significantly shorter than traditional methods. There is, however, one downside to this new design: the drug requires cold storage.
United States company Moderna has a coronavirus candidate vaccine that needs to be kept at minus 20 degrees Celsius, for example. Pfizer’s must be chilled at a continuous temperature of minus 70 degrees. This creates significant problems with its delivery.
The Australian deal with Pfizer includes what Minister Hunt describes as “full cold-chain logistics distribution” and this, as well as the other three vaccines, will be delivered through GPs, hospitals and 147 respiratory clinics from about March.
National Cabinet signed off on a distribution process last week.
Department of Health deputy secretary John Skerritt, who leads the health products regulation group that takes in the TGA, told reporters that as part of its vaccine research Pfizer has developed what are essentially “very sophisticated eskies” packed with dry ice.
“They actually last for 14 days and they can be … refilled twice,” Adjunct Professor Skerritt said.
“So without the need to connect to electricity, or anything like that, these eskies with the two refills gives you a month-and-a-half of cold-chain protection. And even in a country the size of Australia you can get anywhere much quicker than that.”
This poses more significant problems in developing nations, for example, which is one reason the Australian government has set aside a further $500 million to help Pacific island countries secure and administer Covid-19 vaccines.
While the space race was born of a Cold War desire for supremacy, the race for a coronavirus vaccine is the single largest co-operative scientific endeavour in human history.
The logistics alone of providing at least 10 billion doses of a drug in as short a time as possible – Hunt wants all Australians who choose to be vaccinated to have their shots by the end of next year – is impressive. It will change how healthcare is delivered.
Late last week Britain floated plans to launch “mass vaccination centres” in stadiums, conference centres and even a cathedral, with thousands of GPs and nurses across England being redeployed with the help of the armed forces.
And that’s just the beginning.
“We still don’t know if these vaccines provide six months’, 12 months’, five years’ or lifetime protection. No one in the world knows,” Skerritt said.
“And we also don’t know what populations they are suitable for yet. That information comes through in the months and years after a vaccine is approved.”
Australia is currently the vice-chair of a group of international drug regulators that meets often through “endless late-night” video conferences to discuss the safety and efficacy of the candidate vaccines.
“By, say, the end of January we’ll be in a position to be able to give the first couple of vaccines an approval,” Skerritt says.
“And these aren’t the only two. There are at least a dozen companies that we have already been meeting with and discussing in depth … We actually expect there will be a need for a number of different vaccines to cover the market and to cover different groups of patients.”
Last week, analysts at multinational investment bank Morgan Stanley estimated the Pfizer vaccine could generate $US13 billion in global sales next year, split evenly between the pharma giant and BioNTech.
That would vault the candidate – named BNT162b2 – into the lead as the most lucrative drug in Pfizer’s stable, ahead of a pneumonia vaccine that made the company $US5.8 billion last year.
Unlike Moderna and AstraZeneca, which tapped into a multibillion US government fund called Operation Warp Speed to fast-track promising vaccine options, Pfizer stunned watchers by rejecting all government support.
“If it fails, it goes to our pocket, and at the end of the day it is only money,” Pfizer chairman and chief executive Dr Albert Bourla told CBS News in September. “But that will not break the company, although it is going to be painful because we are investing $US1.5 billion, at least, in Covid right now.
“But the reason why I did it was because I wanted to liberate our scientists from any bureaucracy. When you get money from someone, that always comes with strings. They want to see how you are going to progress, what type of moves you’re going to do, they want reports. I didn’t want to have any of that.
“… Basically I gave them an open chequebook so that they can worry only about scientific challenges, not anything else. And also, I wanted to keep Pfizer out of politics, by the way.”
It was a prescient remark, as the Pfizer announcement was immediately drafted into the presidential culture wars. Without any evidence, Donald Trump claimed it was a plot against his re-election, a view that was given succour by conservative commentators on Australia’s Sky News network.
If there are plans on price gouging, they haven’t materialised yet.
Pfizer has agreed to supply 100 million doses to the US at a cost of $US39 for both of the required shots. It has an option to supply another 500 million doses under new terms.
Moderna, which took almost $US1 billion in government research funding, has priced its product at between $US32 and $US37 a dose. AstraZeneca has promised its Covid-19 vaccine to developing nations on an at-cost basis “in perpetuity”.
On news of this week’s breakthrough, Pfizer’s share price shot up 15 per cent to nearly $US42. Its leader, Bourla, automatically sold $US5.6 million of his stock under a predetermined arrangement.
But the market is fickle and the road long.
Before the end of this month, Pfizer will have the minimum two months of efficacy and safety data needed to satisfy the US regulator for emergency approval. Data from the full phase-three trial, which is still under way with 43,538 participants, will be submitted for publication and peer review.
It will take slightly longer for Australia to approve the vaccine, but the expectation is that will happen in January.
This article was first published in the print edition of The Saturday Paper on Nov 14, 2020 as "Fighting fire with Pfizer".
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