The coronavirus vaccine frontrunners have emerged. Here's where they stand
Scientists, drugmakers and governments are moving with unprecedented speed to deliver a vaccine to protect against the new coronavirus.
The fastest of them have already delivered preliminary data from human studies, and further results from others should come quickly as the year progresses.
The goal, at least in the U.S., is to have a vaccine ready for use in some fashion by the end of the year, or early next. Doing so would be a scientific feat with few parallels. No vaccine has ever been developed so quickly, never mind manufactured for the world.
Vaccine frontrunners plan for fast development
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Researchers' success or failure could determine whether the virus becomes endemic, recurring in countries around the world year after year, or is ultimately checked.
With the health of their citizens at stake, governments are investing enormous sums of money into vaccine research and development, and to prepare for manufacturing and distributing what will likely need to be hundreds of millions of doses necessary to keep infection at bay.
With modern-day Manhattan Projects underway, vaccines have become an issue of national security, raising questions of global equity and medicine access.
In the U.S., the Trump administration has unveiled "Operation Warp Speed," pledging billions of dollars of funding and support for an initial, and as yet unconfirmed, slate of candidates.
There's no guarantee the first successful vaccine will come from the U.S., however. Some of the leading candidates are being developed overseas, with projects by China's CanSino Biologics and the University of Oxford in the U.K. the furthest along.
The rest of the world might not be so lucky.
As Emory University vaccines expert Walter Orenstein said in an interview with BioPharma Dive, "It's not like we can expect 7 billion doses the day after licensure so we can vaccinate the whole world." Yet, to truly curb circulation of the SARS-CoV-2 virus in humans, getting vaccines to nations wealthy and poor will be a vital mission.
For scientists, many questions remain unanswered.
The first trials to produce data have avoided any safety issues that can sideline a project for good, and have established they can stimulate an immune response. But what about less common side effects only detectable in massive trials? How good will vaccines be at preventing actual infections?
The next six to nine months should produce a flurry of data, early answers and fresh questions, making it difficult to keep track. Here's where things stand for nine of the most advanced, most promising, or best funded vaccine candidates in the pipeline.
One of the great allures of messenger RNA technology — an unproven approach that instructs cells to produce specific proteins — is that it can be used to make a vaccine much faster than traditional methods. Moderna's experimental coronavirus vaccine is proof.
The vaccine went from a computer design in January to human study in just three months, making Moderna the first U.S. company to reach that point. Since then, Moderna has kept up its record pace. Snippets of Phase 1 data came in late May, as did the start of a mid-stage trial. A final study could begin in July, making the company's efforts one the best hopes for a vaccine that might be available by Operation Warp Speed's hyper-aggressive timeline.
Moderna shares have climbed to all-time highs as the closely-watched program has progressed. But much still needs to go right. No mRNA vaccine has been proven to prevent disease, and none have been manufactured and distributed at scale, let alone during a pandemic.
Moderna hasn't divulged detailed data from its Phase 1 trial, just that its vaccine helped eight people produce antibodies capable of neutralizing the coronavirus in test tubes.
The disclosure, though, left more questions than answers. Whether or not the vaccine is actually protective is still unknown, as is the durability of any benefit. More practically, Moderna still needs to show it can produce enough doses to vaccinate millions of people.
Much as Moderna is the frontrunner in the U.S., China's CanSino Biologics appears to have progressed the furthest among the many Chinese groups researching coronavirus vaccines.
And while Moderna has designed and tested a coronavirus vaccine at record speed, CanSino has moved equally quick.
Around the same time the first trial volunteer received Moderna's shot in Seattle, researchers 6,000 miles away in Wuhan, China were enrolling healthy adults into a Phase 1 study of CanSino's prototype.
Results from that trial were recently published in a peer-reviewed medical journal, allowing CanSino and its Chinese government partners to claim the scientific distinction of being first to do so in the global vaccine race.
Data suggested inoculation spurred immune responses in the 108 participants treated, an encouraging first step. But it's not certain whether the vaccine's effects would actually be protective against infection, and side effects forced researchers to scrap the highest dose.
CanSino's choice of vaccine design may also limit the shot's potential. Pre-existing immunity to the adenovirus, or viral vector, that CanSino uses to deliver its vaccine appeared to compromise its effectiveness.
The company has since advanced its vaccine into mid-stage tests in China and Canada.
Inovio looks to be an underdog in the race, having no big pharma partner and assembling only about $100 million in external funding. But it has moved swiftly, completing dosing in a 40-patient Phase 1 trial, from which it reported "positive results" on June 30.
No detailed data were made available, however, making its claim hard to assess. A Phase 2/3 efficacy trial is expected to begin this summer.
Its candidate uses DNA to coax cells to produce coronavirus proteins, thereby stimulating an immune response to protect against infection by the virus. To allow the DNA molecules to enter cells, Inovio uses a process called electroporation, a small electrical pulse that opens small pores in cells.
One question mark for Inovio will be manufacturing. While it has signed up Ology Bioservices and Richter-Helm BioLogics, it has committed only to producing 1 million doses by the end of the year.
Even that will be complicated by a lawsuit against the companies Inovio contracted to supply its plasmids, VGXI and GeneOne Life Science. Inovio claims they have said they won't be able to sufficiently scale up manufacturing. As a result, Inovio has asked those two companies to transfer the technology to Ology and Richter-Helm.
VGXI and GeneOne have refused, Inovio claims.
Moderna isn't the only biotech aggressively pushing forward with a promising, but unproven technology.
Across the Atlantic, in Mainz, Germany, BioNTech is developing multiple mRNA vaccines for the coronavirus. The drugmaker had already been working with Pfizer on an influenza vaccine for over a year when COVID-19 emerged as a global threat.
The two companies shifted gears toward coronavirus research in mid-March, starting work even before their legal teams had produced a contract.
"The technology was offering speed," said Pfizer CEO Albert Bourla on a recent conference call. "With mRNA technology, you can do in weeks things that for other more conventional technologies you need months."
Pfizer and BioNTech have since started clinical trials in Germany and the U.S. But unlike Moderna and other early starters, the pair are advancing four prototypes, each with subtle differences.
Results from a Phase 1 study of one of those prototypes were disclosed July 1, showing vaccination spurred encouraging immune responses in three dozen healthy adults given the shot. Further data from other early testing could come soon, with a large late-stage trial slated to begin at the end of the month.
Results from the first trials will likely come this month, with further tests to follow quickly thereafter. If "things go well and the stars are aligned," Bourla said, the companies could have a vaccine available for use by the end of October.
That timeline fits well with Operation Warp Speed in the U.S., and Pfizer and BioNTech's program is reportedly among the finalists. But Pfizer won't rely on government funding, saying it can move faster on its own.
Bourla expects the company to spend more than $1 billion on a vaccine.
AstraZeneca became a front-runner in coronavirus drug development when it licensed work by the University of Oxford, which invented one of the first vaccines for SARS-CoV-2 to enter human testing.
Dubbed AZD1222, Oxford's vaccine takes an adenovirus, and much like gene therapies seeking to correct defective DNA, uses it to coax the body's cells to produce the coronavirus' characteristic "spike" protein. The adenovirus used causes infections in chimpanzees but not in humans.
A large Phase 1 study began in late April and should deliver results shortly. Oxford has already advanced the vaccine into mid-stage testing in more than 10,000 Britons. AstraZeneca, meanwhile, has said it could progress to late-stage trials by mid-year, possibly with a 30,000-person Phase 3 study in U.S.
Like others, it may become part of the global tug-of-war over who gets priority. AstraZeneca has said initial supply will go to the U.K., but with the company receiving more than $1 billion in funding from the U.S. government, Americans will be next in line.
Deals struck by Astrazeneca with two health charities and India's Serum Institute will provide for supply elsewhere, particularly low- and middle-income countries, but first deliveriesto CEPI and GAVI aren't expected until the end of the year. As with other large pharmaceutical companies, AstraZeneca has said it will provide vaccine doses on a non-profit basis for the length of the pandemic.
Novavax has spent more than three decades trying to break into a vaccine business dominated by large pharmaceutical companies. Now that it's finally on the brink, with a preventive flu treatment nearing regulatory review, it's become involved in coronavirus vaccine development, too.
Novavax was among the first companies to begin working on a COVID-19 vaccine, and selected its candidate in April. By the end of May, it had not only won a large grant from the nonprofit Coalition for Economic Preparedness Innovations, up to $388 million, but also became one of just a handful of companies to have started a Phase 1 clinical trial. Its shares have climbed nearly 9-fold in the process.
In July, the biotech was further boosted by support from the U.S. government, which committed $1.6 billion to fund late-stage testing of Novavax's vaccine and to buy 100 million doses for distribution as early as the end of this year. Shares climbed by another 30%.
Still, Novavax faces an uphill climb to prove it's technology. Its nanoparticle-based vaccine platform, which uses recombinant proteins to trigger an immune response, has a mixed track record. Before Novavax reported in March that its flu vaccine had succeeded in a Phase 3 trial, two late-stage studies of another potential product for respiratory syncytial virus — a candidate Novavax is still trying to develop — had failed. Other experimental vaccines, among them projects for coronavirus cousins SARS and MERS, never made it to late-stage testing.
A deal with Emergent Bio, and more recently, an acquisition of Praha Vaccine, have given the company the manufacturing muscle to produce over 1 billion doses of its vaccine by next year. But, unlike the larger companies involved with coronavirus vaccine development, making and distributing a product at that scale is something that Novavax has never done.
Merck came late to the coronavirus vaccine race, having publicly announced its efforts near the end of May. But, given its track record developing drugs and vaccines for infectious diseases, its involvement shouldn't be underestimated.
Merck also has no interest in being first. The company is not trying to use new, less proven technologies to move quickly. Instead, Merck homed in on approaches it knows it can manufacture at a global scale, and believes will produce immunity quickly, with one shot.
Those preferences led Merck to license two vaccines that use viruses to deliver their payloads. Merck got one by buying privately held Themis, and the other by teaming up with the nonprofit group IAVI. The Themis vaccine should start its first human tests in July, while the other program will get there later this year.
Both harness technologies with which Merck is already familiar. The drugmaker was working with Themis on a measles-based vaccine for chikungunya, and saw enough to believe the approach could lead to an effective single-dose vaccine, said Daria Hazuda, its head of infectious disease discovery. The IAVI program is based on the same approach behind Ervebo, the company's approved Ebola vaccine.
The company, for its part, believes that will make up ground on its rivals later on, given newer technologies like mRNA and DNA vaccines have never been produced at scale, and may require booster shots to confer immunity.
J&J was first among larger drugmakers to pursue a coronavirus vaccine, announcing in late January plans to develop one using the same technology that underpins several other of the pharma's experimental vaccines.
Initially, J&J didn't expect to begin clinical study until September, a timeline that would have marked record speed previously but in the COVID-19 age appeared more deliberate.
In early June, however, the pharma sped up its plans and now targets the second half of July for the start of its first clinical trial, which will take place in the U.S. and Belgium.
"We are working very much in collaboration with the regulators to further accelerate, to go from Phase 1 to Phase 2 and 3 very quickly," said Paul Stoffels, the pharma's top scientist, on a recent conference call. J&J plans to conduct two large, late-stage studies in North America, Europe and, potentially, countries like Brazil and South Africa. One of those studies may be run in collaboration with the U.S. National Institutes of Health.
Should all go to plan, J&J expects to be able to supply 1 billion doses of its vaccine, beginning early next year.
J&J's scale makes it a natural partner for governments looking ahead to widespread inoculation drives. The U.S. government has pledged over $450 million to J&J's work and the company is one of a handful reportedly selected as a finalist for Operation Warp Speed.
When two of the biggest vaccine manufacturers team up, the world should pay attention to what they're doing. In April, Sanofi and GlaxoSmithKline agreed to join forces, the former contributing its protein-based vaccine technology and the latter its immune-boosting adjuvants, both of which have previously been use against influenza.
They probably won't be the first to market, however. The timeline the two companies have laid out is months behind that of Moderna, Pfizer and even Novavax, which is using a similar approach.
What Sanofi and GSK might be able to bring, though, is a more potent vaccine. Adjuvants are added to vaccines to enhance the immune response, in theory resulting in stronger inoculation against an invading virus. With herd immunity the goal of any mass vaccination program, public health leaders will want a vaccine capable of preventing infections in at least 70% to 80% of the people who get it.
Sanofi and GSK hope to begin human study of their vaccine by September. Already, however, questions over who will have access have been kicked up. Sanofi last month was forced to quickly walk back comments by CEO Paul Hudson that the U.S. would be first in line to get its vaccine thanks to early funding.
Hudon's statement triggered an angry response from French President Emmanuel Macron. Sanofi later clarified Americans would receive doses of its vaccine made in the U.S., while the rest of the world would get doses produced in Sanofi's factories elsewhere.