By Elizabeth Cohen, CNN Senior Medical Correspondent
Updated 7:11 AM ET, Mon November 16, 2020
(CNN)The Moderna vaccine is 94.5% effective against coronavirus, according to early data released Monday by the company, making it the second vaccine in the United States to have a stunningly high success rate….
Vaccinations could begin in the second half of December, Fauci said. Vaccinations are expected to begin with high-risk groups and to be available for the rest of the population next spring.
Last week, Pfizer announced that early data show its vaccine is more than 90% effective against the disease.
In Moderna’s trial, 15,000 study participants were given a placebo, which is a shot of saline that has no effect. Over several months, 90 of them developed Covid-19, with 11 developing severe forms of the disease.
Another 15,000 participants were given the vaccine, and only five of them developed Covid-19. None of the five became severely ill.
So Moderna’s sample size was 95, very similar to Pfizer’s 94. As I pointed out in my Taki’s column, Pfizer very likely could have stuck to its original plan and announced the success of its vaccine before the election (perhaps on Monday, November 2). Whether that would have switched 1 out of 200 voters from voting for Biden to voting for Trump in the 3 states with less of a margin for Biden than 1.0%, which would have led to a 269-269 Electoral College tie and probably a Trump victory in the House voting as state delegations (or perhaps a breakdown in the process with Nancy Pelosi becoming President), is interesting to speculate upon.
In contrast, Moderna’s trial got off to a slower start than did Pfizer’s and its sample size was smaller. They never talked about announcing results in October as Pfizer often had. I haven’t look at their clinical protocol, but my vague impression was their first interim analysis was slated for when 53 cases had been found among their volunteers, not Pfizer’s aggressive plan for a first interim analysis at 32 cases and a second at 64, neither of which was done.
Also, both firms were slowed by the success of their vaccine. Say Pfizer placebo group of 20,000 subjects got a case of wu flu at a rate of 1 per 10,000 per week. So after 8 weeks, the placebo group would have 16 cases, halfway to the first interim analysis’ 32 cases. Now, if the vaccine was total useless, the vaccine arm of 20,000 subjects would have also gotten about 16 cases, so the first interim analysis would be triggered after 8 weeks.
In contrast, if Pfizer’s vaccine was 100% efficacious, then the control arm would have no cases, and it would take 16 weeks for the placebo arm to produce 32 cases.
Instead, both vaccines were apparently somewhere around 95% effective, which made finding enough cases almost as slow as in my toy example of 100% effectiveness. This may have fooled stock analysts into issuing warnings about Pfizer’s price on the grounds that their failure to announce the planned first and second interim-analysis in October was due to the vaccine doing okay but not reaching the criteria for being declared a success from a small sample size. Instead, cases were coming in more slowly, but then when it looked like Pfizer would finally have enough for an announcement just before the election, they halted lab processing of samples to claim deniability: We didn’t KNOW we had 32 cases in the lab, so we didn’t have a “material development” requirement under SEC rules for telling investors.
If Pfizer had announced its vaccine’s success just before the election, The Establishment would have gone into a frenzy of anti-vaxxer conspiracy theorizing, so it was probably the smart call to piss off Trump rather than the media and the guy up 8 points in the polls, even if Pfizer might have to settle some lawsuits from investors over their cover-up.
Initially, there won’t be enough vaccine for everyone. The highest priority groups, which include health care workers, the elderly, and people with underlying medical conditions, will get the vaccine first.
“I think that everybody else will start to get vaccinated towards the end of April,” Fauci said. “And that will go into May, June, July. It will take a couple of months to do.”
So these two messenger RNA vaccines reduce susceptibility to getting COVID by over 90%. A big question remaining is how much do they reduce infectiousness. If they are equally effective at reducing outbound as well as inbound dangers, the vaccines would really do a number on R-nought.
But we don’t know that at present. They ought to do a “human challenge” trial on a Navy ship crewed solely by healthy 20-something volunteers: give everybody on board vaccines. Then after 28 days, inject half with the virus, and see how many of the other half get infected asymptotically. This would be a quite safe experimental design, with only one COVID case expected per every 20 infected, and those volunteers chosen for youth, vigor, and lack of risk factors.
While the two vaccines appear to have very similar safety and efficacy profiles, Moderna’s vaccine has a significant practical advantage over Pfizer’s.
Pfizer’s vaccine has to be kept at minus 75 degrees Celsius. No other vaccine in the US needs to be kept that cold, and doctors’ offices and pharmacies do not have freezers that go that low.
Moderna’s vaccine can be kept at minus 20 degrees Celsius. Other vaccines, such as the one against chickenpox, need to be kept at that temperature.
That means Moderna’s vaccine can be kept in “a readily available freezer that is available in most doctors’ offices and pharmacies,” Zacks said. “We leverage infrastructure that already exists for other marketed vaccines.”
Another advantage of Moderna’s vaccine is that it can be kept for 30 days in the refrigerator [i.e. a few degrees above freezing], the company announced Monday. Pfizer’s vaccine can last only five days in the refrigerator.
I suspect Pfizer’s vaccine would work OK logistically for mass inoculations: e.g., a thousand cars line up in the Dodger Stadium parking lot. But it’s great news to have the less unwieldy Moderna vaccine.
iSteve commenter Jack D writes:
As Steve suggests, the Pfizer vaccine could be distributed to places equipped to handle it and given out on mass vaccination days in big cities and dense suburbs, etc. while the Moderna vaccine could be sent to more rural locations and given out 1 dose at a time at chain drugstores, etc. who already have ordinary freezers. Basically you would send the Pfizer vaccine to the blue counties and the Moderna to the red ones.
TBH, the Pfizer requirements are not that rigorous – my local supermarket has a chest freezer from which they vend dry ice and Fedex and UPS move millions of packages every day. If Omaha Steaks can mail you frozen steaks on dry ice (and they can) then Pfizer can mail frozen vaccines.
The Pfizer vaccine only needs 80 C below freezing for long term (6 month) storage. Dry ice can keep it good for a couple of weeks or so. This isn’t 1970 when every mail order product ad came with the fine print: “Please allow 4 to 6 weeks for shipping & handling.”
From Moderna’s press release:
The 95 COVID-19 cases included 15 older adults (ages 65+) …
It would be useful to know the breakdown among the 15 COVID cases among elders: 5 vaccine / 10 placebo would not be as good as 1 vaccine / 14 placebo. But, at worst, it’s at least 50% effective among people over 65.
The interim analysis included a concurrent review of the available Phase 3 COVE study safety data by the DSMB, which did not report any significant safety concerns. A review of solicited adverse events indicated that the vaccine was generally well tolerated. The majority of adverse events were mild or moderate in severity. Grade 3 (severe) events greater than or equal to 2% in frequency after the first dose included injection site pain (2.7%), and after the second dose included fatigue (9.7%), myalgia (8.9%), arthralgia (5.2%), headache (4.5%), pain (4.1%) and erythema/redness at the injection site (2.0%). These solicited adverse events were generally short-lived.
So, it’s not cost-free. Still …
Preliminary analysis suggests a broadly consistent safety and efficacy profile across all evaluated subgroups. …
The Phase 3 COVE study was designed in collaboration with the FDA and NIH to evaluate Americans at risk of severe COVID-19 disease and completed enrollment of 30,000 participants ages 18 and older in the U.S. on October 22, including those at high risk of the severe complications of COVID-19 disease. The COVE study includes more than 7,000 Americans over the age of 65. It also includes more than 5,000 Americans who are under the age of 65 but have high-risk chronic diseases that put them at increased risk of severe COVID-19, such as diabetes, severe obesity and cardiac disease. These medically high-risk groups represent 42% of the total participants in the Phase 3 COVE study. The study also included communities that have historically been under-represented in clinical research and have been disproportionately impacted by COVID-19. The study includes more than 11,000 participants from communities of color, representing 37% of the study population, which is similar to the diversity of the U.S. at large. This includes more than 6,000 participants who identify as Hispanic or LatinX, and more than 3,000 participants who identify as Black or African American. …
Unlike Pfizer, which was rich enough not to take direct subsidies from the US federal government, but did sign a nearly $2 billion purchase agreement with the Administration, Moderna took just under a billion dollars in direct subsidies and a $1.5 billion purchase agreement:
BARDA is supporting the continued research and development of mRNA-1273 with $955 million in federal funding under Contract no. 75A50120C00034. BARDA is reimbursing Moderna for 100 percent of the allowable costs incurred by the Company for conducting the program described in the BARDA contract. The U.S. government has agreed to provide up to $1.525 billion to purchase supply of mRNA-1273 under U.S. Department of Defense Contract No. W911QY-20-C-0100.