Johnson & Johnson is on the verge of submitting its COVID-19 vaccine candidate for Emergency Use Authorization (EUA) from the FDA. If it is approved, the company would join Pfizer and Moderna as the third vaccine producer for the United States.
“We’re working round the clock,” says Mathai Mammen, global head of research and development for Janssen, Johnson & Johnson’s pharmaceutical division. He’s hoping to get the EUA application for the vaccine submitted by the end of this week and estimates that the approval process will take a few weeks more. If all goes well, members of the American public could receive their shot of Johnson & Johnson’s vaccine as early as March, depending on EUA approval.
There are already signs that the vaccine will be approved: CDC director Rochelle Walensky and Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, spoke at a Friday press conference about what Fauci called the “encouraging news” of Johnson & Johnson’s preliminary Phase III trial results, which had been released that morning. In addition, the American Medical Association has already produced billing codes for the vaccine’s administration.
The Johnson & Johnson vaccine has the potential to reshape a disastrous vaccination rollout in the U.S. and to cement the company’s position in the uncertain future of the pharmaceutical industry. There is “at least an element of sentiment” associated with producing a successful COVID-19 vaccine candidate, says Sam Fazeli, senior pharmaceuticals analyst for Bloomberg Intelligence. “At the end of the day, valuations change when people’s perception of the profitability or the prospects of a company changes,” Fazeli says. Making a vaccine that, unlike the Pfizer and Moderna vaccines, doesn’t require a follow-up appointment and can be easily stored and transported might set the company up for longer-term success.
The vaccine produces a significantly lower level of overall immunity than the Pfizer and Moderna vaccines currently authorized for emergency use by the FDA—66% compared with 94% to 95%. But many experts, and the federal government, say what matters is getting vaccine shots in arms—and the one-shot regimen of the Johnson & Johnson vaccine, combined with its lower storage requirements, will make vaccination possible in settings where the requirements of the other vaccines prohibit their use.
However, the standout immunity offered by the Pfizer and Moderna vaccines has changed the playing field for vaccine makers, and what was once a goal level of immunity is now far below the immunity they can offer. Last year, when vaccine makers rushed en masse to begin developing candidates to treat the emerging pathogen that causes COVID-19, the goal was to produce at least 50% immunity with the vaccine. That level of immunity, which is in the range of what annual flu shots provide, would be enough to make a significant dent in the death and debilitating illness caused by COVID-19.
“If we rewind to a couple of months ago, our standard was, Can we reduce COVID-19 by 50%?” says Dalhousie University virologist Alyson Kelvin. The 94% to 95% immunity offered by the Pfizer and Moderna vaccines “exceeded all of our expectations,” she says. That high immunity makes the lower immunity offered by the Johnson & Johnson vaccine seem less attractive.
But given the pragmatics of vaccination—the difficulties of transporting and storing mRNA vaccines like the ones made by Pfizer and Moderna, the complexities of scheduling a two-dose regimen for every eligible person in the country—and the chaos of the American vaccine rollout so far, a lower-immunity single-dose vaccine with a good record of preventing the worst COVID-19 effects might be just what the doctor ordered, Fauci said in a Monday press conference.
In the making
Johnson & Johnson announced that its Janssen pharmaceutical arm was at work on a COVID-19 vaccine at the end of January 2020—before the disease had reached pandemic levels and even before it had a formal name. Just a few weeks later, the company—like many other prospective vaccine makers—started collaborating with the U.S. Department of Health and Human Services to craft the vaccine.
The company immediately turned to the same vaccine platform—that is, the same modified adenovirus used to deliver the vaccine—as it had used to produce its Ebola vaccine, which was already in human testing at that point and was approved by the European Commission last year.
“We didn’t know it could be a one-shot until we started to get data preclinically and then in Phase I,” Mammen says. After seeing that data, he says, “the immunogenicity was so strong that we knew we could do a one-dose.”
On Friday, Janssen released promising interim data from its Phase III trial. The analysis focused on 468 cases of symptomatic COVID-19 in Janssen’s global study population of 44,325 adults located in South and Central America, South Africa, and the U.S. Over that whole population, the pharma company found that its vaccine was 66% effective in preventing moderate to severe COVID-19. Effectiveness varied by country: It was as low as 57% in South Africa and as high as 72% in the United States.
Mammen points to another statistic: 85%. That’s the level of effectiveness the vaccine achieved in preventing severe COVID-19 in all settings, even in South Africa where a new, possibly deadlier variant of SARS-CoV-2 was recently identified.
“That’s a spectacular result in my eyes,” he says.
High levels of protection against severe disease are especially important because of the long-term debilitating impacts of COVID-19 infection for about 10% of those who contract the disease.
In November, Janssen also started recruiting for a two-dose trial of its vaccine candidate—for the sake of completeness, Mammen says, and to see if the two-dose regimen will produce higher levels of immunity. Results from that trial aren’t likely to be out until late 2021. “Given the results we have right now, I would find it hard to justify the logistical challenge of adding a second dose,” Mammen says.
A one-shot vaccine that doesn’t have the stringent storage requirements of the mRNA vaccines would give health officials the world over “a really good shot of being able to address some critical areas that we haven’t been able to address with the Pfizer and Moderna vaccines,” says University of Manitoba virologist Jason Kindrachuk.
Because it requires only one dose to build immunity and can be stored at home refrigerator temperatures for several months without losing effectiveness, the Janssen vaccine could be a game-changer for low- and middle-income countries as well as rural settings, he says. That, in turn, could speed global economic recovery.
“We are globally interconnected, whether we like it or not,” he says. “What happens in these low- and middle-income regions is going to have secondary effects on us, not just from the side of transmission, but from the side of everything in regards to tourism and trade.”
It might also change the uneven landscape of vaccination in the U.S., the country with the highest per capita rate of identified COVID-19 infections. A CDC report published Monday notes that white Americans, the demographic that has suffered the least from COVID-19, were vaccinated at significantly higher rates than their Black counterparts in the first month of the vaccine rollout. That inequality exemplifies the ongoing health and social disparities that have resulted in a nearly threefold higher COVID-19 death rate among Black, Hispanic, and Native American people, underlining America’s long history of medical racism.
Speaking on a demographic level, Americans of color are more likely to have underlying health conditions and to be served by seriously under-resourced health care apparatuses. Some, like many Native American communities, are more likely to be located in remote areas. As a result, a vaccine that can be kept in a refrigerator and distributed in one dose may be more attainable for those communities. But its lower efficacy raises the question of whether vaccination for COVID-19 will further contribute to the health injustices these communities face.
Indeed, it appears that many public health officials are pinning their hopes on the one-shot vaccine. In today’s press conference, Fauci underlined the importance of achieving high levels of vaccination, even if some of the vaccines are of lower efficacy. And the U.S. has already established orders for more than 100 million doses of the Johnson & Johnson vaccine. The company says it will be ready to start shipping some of its already manufactured doses as soon as it gets an EUA, likely within days.
Vaccines have become big business
Producing any working vaccine against COVID-19 is a huge achievement. Historically, Kindrachuk says, “coronaviruses were kind of seen as being an annoyance more than anything else.” Although the deadly SARS outbreak of the early 2000s and the identification of MERS in 2012 increased interest in producing coronavirus vaccines, neither of those viruses, fortunately, reached pandemic levels.
As a result, Kindrachuk says, vaccine makers focused their efforts elsewhere, using advances in biotechnology to produce more effective or safer vaccines against known pathogens and vaccines against pathogens that never had a vaccine before, such as Ebola and human papillomavirus (HPV). They also focused on emerging pathogens like Zika.
That all changed with the outbreak of the COVID-19 pandemic, which is caused by SARS-CoV-2. More than a year since its arrival, the virus has killed more than 2 million people globally and left many thousands with so-called long COVID, debilitating systems that may last months or even longer. Some therapeutics have been found to help those with severe COVID-19, but, by and large, hope still rests on the world isolating until a significant percentage of the global population can be vaccinated.
A flood of development funding and attention has transformed the pharmaceutical sector. Previously marginal companies such as Novavax and AstraZeneca have reached the forefront of global pharmaceuticals news because they have developed successful vaccine candidates.
But mRNA is “a bit, we can say, delicate,” says Kelvin. “We have to wrap it up well so that it can be delivered properly into cells.” In the case of the Moderna and Pfizer vaccines, lipid nanoparticles—tiny particles of biological material that mimic the cell membrane—encapsulate the mRNA and keep it safe until it can deliver its information to human cells.
Once in the cells, the mRNA codes for the production of the coronavirus’s characteristic spike protein that it uses to enter human cells. The vaccinated person’s own cells produce the protein, which the immune system then identifies and learns how to fight against. The mRNA doesn’t hang around for very long, and its components are broken down and recycled with other cellular material.
This approach has been demonstrated to work extremely well, says Kelvin, but it’s a new one, and the duration of the immunity it imparts is still unknown. Both the AstraZeneca and now the Johnson & Johnson vaccine candidates take a more traditional approach to provoking the human immune response. They use inactivated forms of other viruses to deliver the genetic information. That approach might lead to longer-lasting immunity, Kelvin says, although it’s too soon to know.
Johnson & Johnson plans to sell the vaccine at cost, at least during the first phase of the pandemic. The company says the price will not exceed $10 per dose—which is substantially lower than the Pfizer and Moderna vaccines, both of which are being sold at profit. It’s unclear what that will mean for the company’s profitability in the short term, if anything, but the reputational gain of producing a successful vaccine candidate may be significant, as it has been for other drugmakers. “How many people knew who Moderna was before now?” asks Arizona State University regulatory scientist JoAnn Pfeiffer.
The impact of lower efficacy
News reports since the release of Janssen’s preliminary Phase III results on Friday have largely focused on its much lower overall efficacy in provoking an immune response. But University of Manitoba’s Kindrachuk says it’s hard to compare the Moderna and Pfizer products to other vaccine candidates that also exceed the 50% immunity threshold.
“While Rolls makes amazing cars, we can’t really compare other vehicles to their products all of the time,” he told Fortune by email after the news broke. “The assessments need to be made on how well the product works given the circumstances.”
But the standout immunity offered by the Pfizer and Moderna vaccines does create ethical questions when compared with the lower immunity of Johnson & Johnson and other vaccines, says Dalhousie University’s Kelvin. “It changed the way that we are considering a vaccine that we want to be using in our public,” she says. “Because they’re so effective that giving people less effective vaccines is perhaps not ethical.”
The approval of the Johnson & Johnson vaccine would change the approach of the U.S. to COVID-19 vaccination. Less than two months into a disastrous rollout, that might be warranted, but the stakes of a decision to use a lower-effectiveness vaccine now when a higher-effectiveness vaccine will become available later can be measured in lives.
Then there’s another consideration that is worrying scientists: A partially vaccinated population with a mix of immunity levels creates exactly the immunity pressures that SARS-CoV-2, the virus that causes COVID-19, needs to mutate and adapt past our defenses. Vaccinating people with a less effective vaccine, while it will save lives now, might thus result in far more deaths later if the virus can successfully out-adapt the vaccines and other treatments we use against it.
When the virus does mutate, as all viruses do, Mammen says, Janssen’s vaccine platform can be easily modified along with it. “On the manufacturing side, we make a piece of DNA, which is easy, and we put it in exactly the same platform,” he says. “It slots right in to all the work we’ve done over the past year.”
And that mutation could be good news for vaccine makers. “If the virus is evolving in a way that means we need booster shots, that changes the fundamental value of these companies,” says Bloomberg Intelligence’s Fazeli. “If you need to sell yet another 2 billion shots next year, that makes this recurring revenue instead of one-off revenue.”
Johnson & Johnson’s prospects and the company’s exact meaning when it says its vaccine will be sold at cost should become clearer after its first-quarter earnings call in April, Fazeli says. For now, Johnson & Johnson is ready to join what has been a nightmare of a rollout in the U.S., and its vaccine is poised to help turn the tide.