The novel coronavirus has driven whole countries into quarantine and wreaked havoc on the global economy. And the quickest way to fight it may be with the help of an unproven technology.
That technology, which uses messenger RNA, or mRNA, molecules to coax the body into producing proteins, is in the spotlight Tuesday as the Cambridge, Massachusetts-based biotech Moderna holds an investor event on its efforts to develop mRNA vaccines.
Moderna has seven preventive vaccines for infectious diseases in human testing thus far, for Zika, cytomegalovirus, influenza and other viral pathogens. Each offers the chance to prove the worth of mRNA vaccines, which, while faster to design and produce than their traditional protein-based counterparts, have yet to show they can work just as well.
"The jury is out on what problems might still arise or where we might find hang-ups," said Jonathan Watts, an associate professor at the RNA Therapeutics Institute at University of Massachusetts Medical School, who doesn't have ties to Moderna. "But I'm cautiously optimistic that this could be a game-changing technology for things that have been really hard until now."
Moderna is making its case on the biggest possible stage. The coronavirus continues to spread across the globe — killing more than 120,000 people as of Tuesday, according to data collected by Johns Hopkins University — and mRNA technology could underpin the first vaccine against it.
CEO Stephane Bancel said Moderna began working on one in January. By March, its vaccine became the first to enter human study for SARS-CoV-2 — far faster than typical. Other mRNA vaccines from CureVac, BioNTech and Translate Bio could follow as soon as this summer, and their progress will be critical in meeting the 12- to 18-month timeline government officials have cited for a coronavirus vaccine. Other efforts, including for DNA-based vaccines, are proceeding rapidly as well.
"We feel a sense of unique privilege — but unique responsibility — to get this right," said Moderna's chief medical officer Tal Zaks in an interview. "The pressure we've put on ourselves is probably the highest it's ever been in my professional career."
Thomas Russo, the chief of infectious disease at the University of Buffalo's Jacobs School of Medicine and Biomedical Sciences, views the aggressive timeline as "feasible if we really hit a home run." But a lot will have to go right for that to happen.
There hasn't yet been a vaccine, let alone an mRNA vaccine, for any of the seven types of coronavirus known to infect humans. Drug developers are leaning on past scientific work on other coronaviruses. That's led Moderna and others to focus on a distinctive "spike" protein seen on the surface of SARS-CoV-2. Moderna's vaccine, dubbed mRNA-1273, tells the body's cells to produce that spike protein, which, in theory, triggers the creation of antibodies to fight off a coronavirus infection.
Zaks said the approach is based on research on the SARS virus, a genetically related but different coronavirus, which showed that getting the body familiar with the spike protein alone would be enough to do the trick. But that isn't guaranteed. Russo at the University of Buffalo said there is some concern among experts that a coronavirus vaccine might need to target other surface proteins, too, for the body to generate a durable immune attack.
Zaks argues the scientific data supporting that theory is "weak and not mentally strong" enough to "dilute the effort that we have." If he's right, the data supporting his case will begin to emerge in the coming months, beginning first with early proof that mRNA-1273 is safe, and later, that it spurs the body to produce enough coronavirus-fighting antibodies.
Moderna's plan is to start a mid-stage trial early in the summer and then, assuming success, pivotal trials — the large efficacy studies supporting potential approval — in the fall.
Fast progress would leave regulators with a tough task. Because preventive vaccines are given to healthy people, they are typically approved only after large studies in thousands of patients show they're safe and can prevent infections, not just proof of surrogate markers that might lead to those outcomes.
The Food and Drug Administration, though, will face enormous pressure to be flexible with a coronavirus vaccine that shows potential. Will it wait for fuller proof? Or, if early data are compelling, approve it on a limited, emergency basis? That decision will be made tougher by the fact that methods to measure the presence of coronavirus-fighting antibodies are "still being built and tested as we speak," Zaks said.
The FDA "understands the gravity of the situation," Zaks said, and is looking at "all possible pathways" to determine the risks and possible benefits of mRNA-1273.
"It's going to be up to the government to figure out the right trigger point," Zaks said. "Our job here is to advance this and collect the data as quickly and as diligently as possible."
In the meantime, Bancel said Moderna is scaling up manufacturing with the hope of being able to produce "millions of vials per month" by Christmas and "tens of millions" monthly next year. The biotech is not anticipating that everyone would need a vaccine. Instead it's more likely vulnerable populations like healthcare workers and the elderly would receive treatment first.
The fast rise of Moderna's coronavirus vaccine, meanwhile, represents a major opportunity for validation. The company has been best known for raising money hand over fist through through partnerships, venture rounds and biotech's biggest-ever initial public offering. Moderna has steadily accumulated early data across a variety of programs showing its vaccines can help produce an immune response, but has yet to show these vaccines can prevent disease.
The most substantial evidence has come in cytomegalovirus, a congenital infection that can cause birth defects. But Moderna's shares have only risen above their IPO price over the past couple months, reaching record highs of near $35 apiece as the company's coronavirus work has progressed.
Much of Moderna's other vaccine work, meanwhile, is being disrupted by the pandemic's effects on clinical trials across the globe. Though Zaks said Moderna is still on track to start a Phase 3 trial in cytomegalovirus next year, there will likely be some "missing data," in the ongoing Phase 2 study, he said.