Wall Street investors, local health departments, and political leaders can all be excused if Monday’s Moderna coronavirus vaccine announcement has them feeling a bit whipsawed. Buyer’s remorse has heads spinning from Pfizer’s SARS-CoV-2 vaccine to Moderna’s. Get used to it. With more than 200 vaccines in development, there will be months of confusion and tougher choices ahead.
Based on press releases—which is all the world has at this point to work with—the COVID-19 vaccine announced last week by Pfizer and BioNTech, which uses mRNA as genetic code for the spike proteins that protrude from the surface of spherical viruses, offers more than 90 percent protection after recipients had two doses administered. But the product is highly unstable, requiring storage and transport in freezers that can hold temperatures below minus 100 degrees Fahrenheit.
The Moderna vaccine, which is also an mRNA-based American-made products, was 94.5 percent protective for volunteers who received two doses but were tested for infection after two weeks. And it is a more stable product that can be safely stored in standard commercial deep freezers, at minus 4 degrees Fahrenheit. It can even safely sit for up to 12 hours at room temperature, according to a Moderna press release.
“To me the surprise is not that the efficacy looks great, but that the stability is better, which makes vaccination campaigns significantly easier,” said Jaap Goudsmit of the Harvard T.H. Chan School of Public Health. Richard Hatchett, the CEO of the Coalition for Epidemic Preparedness Innovations, echoed Goudsmit, saying Moderna’s results are “as good as we could have hoped for. … The fact that the vaccine shows stability when stored in a normal refrigerator for up to 30 days is also terrific news and will allow the vaccine to be distributed broadly,” even in remote areas and poorer countries.
There are more vaccines in the pipeline, to be announced in similarly scant press releases before the inauguration of U.S. President-elect Joe Biden on Jan. 20. This leaves the challenge of sorting out the science and comparing the various products’ safety and efficacy to a lame-duck U.S. Food and Drug Administration (FDA). And immunization instructions to U.S. states and territories, including equipment purchasing and personnel hires, are left to an also lame-duck Centers for Disease Control and Prevention (CDC) leadership.
Both agencies are under pressure from President Donald Trump’s Operation Warp Speed mandates to rush emergency use authorizations for the vaccines and instructions to doctors and states at record speeds. In his first public appearance since losing the Nov. 3 election, Trump on Friday in the White House Rose Garden laid claim to the Pfizer breakthrough, describing his personal vaccine efforts as “unequaled and unrivaled.” In a tweet on Monday, the president wrote, “Another Vaccine just announced. This time by Moderna, 95% effective. For those great ‘historians’, please remember that these great discoveries, which will end the China Plague, all took place on my watch!” Both Vice President Mike Pence and Trump’s son-in-law, Jared Kushner, claimed the vaccines as Trump triumphs. As the conservative commentator Hugh Hewitt put it, the “COVID-19 vaccine should be Trump’s legacy.”
On Wall Street, stocks soared with each vaccine announcement, with Moderna’s pushing stock values for Pfizer and its German vaccine partner, BioNTech, down. Future vaccine announcements are likely to send jolts through the markets, as well. Indeed, with the first two horses out of the gate running such strong races, said the immunologist John Moore, it’s “a very good indicator that most, and perhaps all, of the Operation Warp Speed vaccines will turn out to be valuable for curtailing the pandemic during the first half of 2021.”
There are 53 vaccine candidates in human clinical trials worldwide right now, and another 155 are further back in the research and development pipeline. To put this in perspective, between January 2010 and June 2020 the FDA approved 21 new vaccines, which underwent a median of eight years of development and seven clinical trials, creating mountains of data on which to judge their safety and efficacy. In contrast, less than 10 months of R&D and just two small, fast clinical trials’ worth of data are all the COVID-19 vaccines are bringing to the FDA for judgment. Nearing completion of Phase 3 clinical trials are a protein vaccine from Novavax; several viral vector products made by Johnson & Johnson, Britain’s AstraZeneca, China’s CanSino, and Russia’s Gamaleya Research Institute; and whole inactivated SARS-CoV-2 viruses already being used in China, made by Sinovac. As promising as the Moderna and Pfizer products seem to be, it is possible one of these 208 vaccines will prove even better.
There is much to smile about. But wait, even Moderna’s own press release warns that the euphoria of the moment just might be a mirage: “The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna’s control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements.”
Yes, warns Moderna, there’s plenty to give you pause because “there has never been a commercial product utilizing mRNA technology approved for use; the fact that the rapid response technology in use by Moderna is still being developed and implemented; the fact that the safety and efficacy of mRNA-1273 has not yet been established; despite having ongoing interactions with the FDA or other regulatory agencies, the FDA or such other regulatory agencies may not agree with the Company’s regulatory approval strategies, components of our filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data submitted; potential adverse impacts due to the global COVID-19 pandemic such as delays in regulatory review, manufacturing and clinical trials, supply chain interruptions, adverse effects on healthcare systems and disruption of the global economy.”
Science by press release, versus peer-reviewed medical journal publication, is clearly unsatisfactory. It is made more so when the corporate leaders touting their vaccine products sell off their company stocks to realize large personal fortunes—$5.6 million worth for Pfizer’s CEO and $50 million for Moderna’s chief medical officer. It’s hard to accept press release claims when the statements spawn fortunes for the individuals in charge of the data.
Sorting out whether or not the Pfizer, Moderna, and forthcoming vaccines actually work as claimed in their respective press releases, are safe, and provide lasting protection against SARS-CoV-2 is the job of the FDA, where Stephen Hahn reigns as commissioner until Jan. 20—or until Trump fires him. With other political appointees and a staff of scientists who have been denigrated by White House officials for four years, Hahn will determine whether to grant emergency use authorizations to the products, granting legal temporary use in lieu of more exhaustive testing and licensure. These decisions will be made in the coming weeks based on standards of approval created by the Trump administration, and the Biden team will have little or no say in a process that will saddle it with chosen products and billions of dollars in subsidy payments and already committed purchases.
Similarly, Robert Redfield and his CDC staff are making decisions now regarding how the vaccines will be distributed, to whom, and with what equipment and talent pool required at the state level. For the states, the stakes are high, as the CDC has promised only $340 million in assistance so far; state health departments have asked for $8.4 billion, and even Redfield concedes that localities need at least $6 billion to pull off mass two-dose immunization of all U.S. residents. Few states have the ability to track all of their citizenry, keeping count of who receives a first dose of vaccine and who their second. The cost difference for states between a refrigerated Moderna vaccine program versus a deep-frozen Pfizer one is substantial. Governors not only want more money but clear guidance and advice from the federal government, little of which is forthcoming.
Here, too, the Biden team is denied access to the CDC and input into immunization decisions that could prove very costly to the states—and therefore difficult to alter should the Trump administration plans prove unsatisfactory. As a go-around, sidestepping Trump’s intransigence, Biden; his chief of staff, Ronald Klain; and members of his COVID-19 task force are meeting directly with vaccine manufacturers.
Comparing the various vaccines will be difficult, as a great deal about the normal human immune response to SARS-CoV-2 infection remains mysterious, including which components of the immune system are pivotal, how long people may be protected by antibodies, and how commonly they may be reinfected. Each one of the vaccine manufacturers is using its own criteria for measuring antibodies and other aspects of volunteers’ immune responses.
The supposed efficacy differences between the Pfizer and Moderna vaccines, for example, are not significant, given the very small numbers of COVID-19 cases they represent. Temperature sensitivity is a much more important issue and one that might swing the balance toward Moderna.
The key difference between the Moderna and Pfizer products is the liposome packaging the companies invented to carry their mRNA in vaccine form and get it inside living human cells. In the Pfizer case, the liposomes must be kept frozen to prevent them from falling apart. Moderna has invented a far superior type of liposome, but its details are a trade secret. Even inside cloistered FDA meetings it will be difficult for agency scientists to garner and compare liposome details. And similar issues will arise with the patented details behind every vaccine that comes to the FDA for an emergency use authorization or license approval.
America’s epidemic is completely out of control, with more than 11 million cumulative cases of COVID-19 and a quarter-million deaths as of Nov. 17. There is good reason to rush a vaccine to use, slowing the human carnage and allowing businesses to reopen, fueling the economy. But the strategies and assessments are being made now by one administration and handed as faits accompli to another. For example, according to Fox Business, the Trump administration has ordered 100 million doses of the Pfizer vaccine, worth $1.95 billion, with the option of buying 500 million more. The European Union has ordered 200 million doses with the possibility of 100 million more, the U.K. 30 million doses, and Japan 120 million. Now that the Moderna vaccine seems more stable, thus easier to use, the shopping spree at Pfizer might boil down to a buyer’s remorse headache that Biden and American taxpayers will be stuck with.
And the Moderna vaccine that looks so hot in mid-November could well be overshadowed by an even better product come December. “There are many, many questions still remaining about the duration of protection, the impact on severe disease, the impact on different subpopulations, especially the elderly, as well as the adverse effects beyond a certain period of time,” warned Soumya Swaminathan, chief scientist at the World Health Organization.
When you’re racing at warp speed, there are bound to be surprises ahead. And much to the chagrin of Biden’s COVID-19 task force, the terms of Operation Warp Speed and the assessment of vaccine products are matters before the Trump administration—for which it’s all in the art of the deal, at taxpayers’ expense.
