The first coronavirus vaccines have arrived. Here's where the rest stand.
Scientists, drugmakers and governments have moved with unprecedented haste to develop a vaccine against the new coronavirus.
The fastest of them have completed studies proving their vaccines can protect against COVID-19. A half dozen shots from developers in the U.S., U.K., Germany, China and Russia have now been cleared by regulators for emergency use.
Their success is a scientific feat with few parallels. No vaccine has ever been developed so quickly, never mind readied for widespread use.
Vaccine frontrunners have progressed quickly
With the health of their citizens at stake, governments invested enormous sums of money into vaccine research and development, and to prepare to manufacture and distribute what will likely need to be billions of doses necessary to keep the pandemic at bay.
The immunization campaigns that are just now getting underway will help determine whether the virus becomes endemic, recurring year after year, or is ultimately checked.
The frenetic race to develop a vaccine, and to secure supplies of the leading candidates, has led to political jockeying between governments, however. Russia, seeking a Sputnik-like achievement to tout to the world, approved a vaccine before testing was complete, while China cleared experimental shots for limited domestic use early on. The Trump administration, meanwhile, pledged more than $11 billion in funding for seven candidates through "Operation Warp Speed."
Initial doses of authorized vaccines are in short supply, and early access has largely been dictated by lucrative deals struck between drugmakers and governments. Yet, to truly curb the spread of the SARS-CoV-2 virus, getting vaccines to nations wealthy and poor will be a vital mission.
Here's where things stand for 14 of the most advanced, most promising or best-funded vaccine candidates. Use the menu on the left to jump to a developer.
One of the advantages to messenger RNA technology — a drug-making approach that uses genetic instructions to teach cells to make specific proteins — is that it can be used to build a vaccine more easily than traditional methods. Moderna's 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.
Moderna kept up its record pace in the months since then. Snippets of Phase 1 results came in late May, as did the start of a mid-stage trial. A Phase 3 study began on July 27 and, four months later, delivered strongly positive results that indicated the vaccine was 94% effective in preventing COVID-19. Data shared by Moderna also show the vaccine protects people from the severe disease that leads to the worst health outcomes.
The finding was a powerful — and hopeful — result. Taken together with a similarly positive readout from Pfizer and BioNTech, which in mid November said their shot was 95% effective in preventing COVID-19, researchers could be sure that mRNA vaccines were protective.
Crucially, Moderna's vaccine also appeared safe, with no unexpected or serious side effects. The company formally asked the Food and Drug Administration for emergency approval on Nov. 30 and a panel of agency advisers endorsed the vaccine on Dec. 17. Just one day later, the FDA granted authorization for the shot, marking a milestone for both the U.S. public health response to the pandemic and for the decade-old biotech.
Initial supplies are limited to several tens of millions of doses, although the company and its manufacturing partners expect to greatly ramp up production in 2021.
Moderna has come under scrutiny, too, both for the price it charged the U.S. government as well as for the intellectual property it claims for its vaccine. Government scientists have supported Moderna's work and could hold rights to some of the underpinning technology. Moderna has said it will not enforce patent rights related to its vaccine technology for the duration of the pandemic.
CanSino had the distinction of being among the first to begin testing its vaccine in humans, report early data and start immunizations outside of a clinical study. But those milestones have faded as the company has struggled to complete a large Phase 3 trial and obtain the kind of proof regulators outside of China would need to authorize use.
Early and mid-stage trial results were sufficient to persuade the Chinese military to clear emergency use of CanSino's vaccine in soldiers. Declining COVID-19 cases in China, however, pushed CanSino and other Chinese vaccine developers to seek study sites overseas.
CanSino, which has ties to Canada, had originally intended to study its shot in Canada, but an agreement there reportedly came undone.
A large late-stage study is now recruiting volunteers in South America, Mexico, Pakistan and Russia, with a goal of enrolling 40,000 and reporting data by Jan. 30, 2021.
CanSino's choice of vaccine design may limit the shot's potential, though. Early studies showed pre-existing immunity to the adenovirus, or viral vector, that CanSino uses to deliver its vaccine appeared to compromise its effectiveness.
Inovio has fallen behind in the race to develop a coronavirus vaccine, having no big pharma partner and assembling only about $100 million in external funding.
A partial clinical hold imposed by the FDA in late September, meanwhile, kept the company from conducting further study of its vaccine candidate until mid-November, when the agency cleared a Phase 2 trial to begin.
Inovio's 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. The device used to do this was the subject of some of the FDA's concerns, which the company plans to address via the Phase 2 trial.
Should those questions be resolved, Inovio would then launch a Phase 3 trial that remains on partial clinical hold. But it's not clear when that might be. More than a month passed between Inovio's announcement it was initiating the mid-stage study and when the first volunteer was vaccinated on Dec. 14.
Summary data from a small Phase 1 trial were disclosed by the company in June, and published in a medical journal on Dec. 24. Vaccination was safe and spurred immune responses against the virus. Those responses appeared weaker than what's been reported for Pfizer's and Moderna's shots, however.
Inovio's manufacturing capacity is also much less than that of Pfizer and Moderna, although the biotech has boosted its supply lines. Inovio recently signed Thermo Fisher to its manufacturing consortium, with the hope of producing 100 million doses in 2021. An initial round of manufacturing deals, with Ology Bioservices and Richter-Helm BioLogics, would have produced only 1 million.
Inovio's production plans, however, are threatened by ongoing litigation involving two companies, VGXI and GeneOne Life Science, that were contracted to supply materials for its vaccine. Inovio had sued the two companies, claiming they refused to transfer technology to Ology and Richter-Helm. VGXI countersued, charging breach of contract and other claims.
In the U.S. and Europe, vaccine developers bet on newer technologies, such as messenger RNA or viral vectors, that, while less established, offer crucial advantages in speed. Sinovac, along with several other companies and institutions in China and India, however, have moved almost as quickly using the tried-and-true approach of inactivated virus vaccines.
Used for hepatitis A, influenza and rabies, these vaccines consist of viruses rendered uninfectious either through heat or harsh chemicals.
Sinovac wasn't the first to get going, but was able to obtain results from late-stage testing faster than several more closely tracked Western drugmakers. While initial reports of data from a study in Brazil suggested strong efficacy, later announcements put the shot's overall efficacy just over 50% — barely clearing a bar set by regulators around the world.
The higher figure, researchers in Brazil said, was from counting only COVID-19 cases that required medical assistance. Comparing protection against COVID-19 of any severity resulted in a lower number.
The incomplete disclosures added to confusion over Sinovac's vaccine, particularly as researchers running studies in Turkey and Indonesia also reported differing results.
The shot was reportedly approved in China in late August for emergency use in people at high risk of coronavirus infection.
Sinovac is listed on the Nasdaq stock exchange, but trading in its stock has been halted since February 2019 — the result of a dispute with an activist investor over control of the company.
Moderna wasn't the only biotech to aggressively push forward with the promising, but until now unproven, messenger RNA technology.
Across the Atlantic, in Mainz, Germany, BioNTech started work on an mRNA vaccine for the coronavirus early on and agreed to partner with Pfizer in mid-March, joining forces with the larger drugmaker even before their legal teams had produced a contract.
The partnership turned out to be a historic one, with the two companies winning clearance from the U.K. drugs regulator for their shot just eight months later, followed quickly by authorization in Canada on Dec. 9 and an emergency clearance from the FDA on Dec. 11. Authorities in the EU granted conditional authorization on Dec. 21.
The U.K.'s decision was a world first for a coronavirus vaccine that had completed testing; earlier vaccine approvals in China and Russia were done before late-stage studies had begun.
Unlike Moderna and other frontrunners, Pfizer and BioNTech had initially advanced four prototypes, each with subtle differences, before choosing one to take into late-stage testing. A Phase 2/3 trial began on July 28 and enrolled some 44,000 volunteers over the course of three months.
Data from the trial have now been published in the New England Journal of Medicine, affirming earlier positive results and demonstrating a better-than-expected 95% efficacy in preventing COVID-19. The finding was based on 170 cases of COVID-19 counted beginning one week after the second dose. Only eight were in study participants who received the vaccine.
Side effects are primarily injection site pain and other common vaccine reactions like fatigue and fever. Moreover, regulators are watching closely for allergic reactions after a handful of cases in the U.S. and U.K. following vaccination.
The companies have contracted to supply the U.S. with 200 million doses, although only several million were ready to be shipped immediately after the FDA's authorization. Unlike others, the drugmaker hasn't relied on government funding for testing and manufacturing, claiming it's been able to move faster on its own.
BioNTech did receive nearly $450 million from the German government, however, to support vaccine development — money the biotech will use to cover its share of expenses in the partnership.
When Chinese scientists made the new coronavirus' genetic sequence available in January, researchers at the University of Oxford were more prepared than most.
A team there was already working on a vaccine for the virus that causes MERS, a close cousin of SARS-CoV-2. The Oxford researchers quickly adapted their work and, by April, had started a large Phase 1 trial of their new vaccine in the U.K.
AstraZeneca signed on to help soon after, licensing the vaccine and beginning efforts to prepare for manufacturing hundreds of millions of doses.
Their speed — larger studies began in May, June and September — made AstraZeneca and Oxford's vaccine among the world's leading efforts and the subject of political tug-of-wars over who would get access.
But the program hit several setbacks, beginning in early September when AstraZeneca and Oxford halted testing worldwide after one participant in the U.K. study fell sick with an unexplained neurological illness.
While regulators in the U.K. and other countries quickly signed off on a trial restart, a review by the FDA took much longer, dragging on for more than six weeks before the agency gave AstraZeneca a green light on Oct. 23 to resume vaccinations.
In late November, AstraZeneca shared preliminary data from studies in the U.K. and Brazil showing its vaccine could protect against COVID-19. Yet the positive results were confusing, showing dramatically different protection rates between a larger group that received two full doses of the shot and a smaller group that was given a half dose and then a full dose. Moreover, the half dose was the result of a manufacturing error, AstraZeneca later acknowledged.
Despite the confusion, the U.K. drugs regulator authorized the shot about a month later, clearing the two full dose regimen given to the majority of participants in the U.K.- and Brazil-based studies.
In mid-January, outgoing Operation Warp Speed chief Moncef Slaoui said a large U.S. trial has completed recruitment and, if successful, could lead to an authorization in March. Another study may also be launched to clear up the confusion over the mixed data from the U.K. and Brazil studies.
AstraZeneca and Oxford's vaccine is viewed as important for global immunization efforts as it can be more easily distributed and stored. AstraZeneca has also committed to sell doses more cheaply than others, and expects to produce a greater number of doses.
While the Western world has focused on leading candidates from large multinational drugmakers, China's state-owned Sinopharm has advanced two inactivated vaccines through late-stage trials and to approvals in the UAE and Bahrain.
Early-stage studies began in April for both of Sinopharm's candidates, data from which were published in JAMA in August and The Lancet in October, respectively. In each case, vaccination via two injections was generally well tolerated and triggered immune system responses against coronavirus proteins.
Like other Chinese vaccine developers, however, Sinopharm was forced to test the experimental shots outside of China once the virus' spread was brought under control in the country.
The company, a sprawling conglomerate and vaccine maker, turned to the Middle East and to South American for launching Phase 3 trials, the first of which began in July.
A late-stage study in the UAE of one candidate, created by the Sinopharm subsidiary Beijing Institute of Biological Products, quickly enrolled and was expanded into Bahrain, Egypt and Jordan, with a target recruitment of 45,000 volunteers.
The UAE granted emergency authorization for the Beijing Institute shot in mid-September, followed by a full approval in December. A short announcement from the UAE health ministry indicated an interim analysis of Sinopharm's trial found vaccination was 86% effective, although no details were given to support that claim.
On Dec. 31, the Chinese government said it had conditionally approved the vaccine, citing new data from the Beijing Institute that put the shot's efficacy at 79%. "Millions" of doses have already been used to vaccinate healthcare workers and people who work overseas under an emergency use program, China's health ministry said.
The vaccine is also approved in Bahrain.
Sinopharm's other shot was developed by another unit of the company, the Wuhan Institute of Biological Products, and is being studied in Phase 3 trials in the UAE, Morocco, Argentina and Peru.
Novavax, which has spent more than 30 years trying unsuccessfully to develop vaccines, was among the first companies to begin working on a coronavirus shot. By the end of May, the Maryland biotech had won a large grant from the nonprofit Coalition for Economic Preparedness Innovations and started an initial clinical trial, boosting its shares nearly 9-fold in the process.
In July, the biotech secured 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.
Results from Novavax's Phase 1 study showed its vaccine spurred encouraging immune responses. Like other experimental shots, vaccination was associated with mostly mild side effects in most trial participants. A late-stage study began in the U.K. in late September, and enrolled its target 15,000 participants in a little over two months.
Progress slowed in the U.S., with at least two delays to a Phase 3 trial that finally got underway on Dec. 28. The trial is also being conducted in Mexico and is designed to involve 30,000 volunteers. By mid-January, around 8,000 participants had been enrolled, according to Warp Speed's Slaoui.
Novavax's vaccine platform, which uses recombinant proteins to trigger an immune response, has a mixed track record. Before the company reported in March the success of its flu vaccine, two late-stage studies of a potential shot for respiratory syncytial virus failed. Other experimental vaccines for coronavirus cousins SARS and MERS never made it to late-stage testing.
Russia approved Gamaleya's vaccine on Aug. 11, less than two months after the first studies in humans began and, critically, before large-scale trials had proved whether it could protect against COVID-19.
The approval, which was announced by President Vladimir Putin, was the most significant example to date of how the race to develop a coronavirus vaccine has been cast in geopolitical terms.
Like the U.S., China and Europe, Russia pushed for fast development, spurring concerns that safety risks might go overlooked or crucial steps bypassed.
In the case of Gamaleya's vaccine, the government's urgency led to an approval following two small trials in just 76 volunteers. Such studies are designed to get an early sense of a vaccine's safety, as well as whether the shot spurs an immune response.
That data was published on Sept. 4 in The Lancet, showing Gamaleya's vaccine stimulated an immune response equal to that of patients who have recovered from coronavirus infections. However, shortly thereafter, several dozen scientists penned a "letter of concern" regarding possible inconsistencies in the data shared by Gamaleya researchers.
Proving protection from either coronavirus infection or disease requires larger, placebo-controlled tests involving thousands of participants. Gamaleya, with help from Russia's government and sovereign wealth fund, got started on a late-stage trial of its vaccine in late August, as the government was already beginning to distribute the shot.
On Dec. 14, Gamaleya released detailed data from that study, which gave 22,714 volunteers either the shot or a placebo. There were 62 cases of COVID-19 in patients who received the sham injection and 16 in the those who got the vaccine.
Because three times as many trial participants received the vaccine as did placebo, Gamaleya calculated efficacy against COVID-19 as more than 91%. The institute said it will submit the data to a peer-reviewed medical journal for publication.
In the meantime, Gamaleya has begun working together with AstraZeneca, pairing the special virus it uses to deliver its shot with one used by the British drugmaker, a move aimed at improving the efficacy of AstraZeneca’s vaccine.
Vaccinations with GRI's shot have begun in Belarus as well, according to the Russian health ministry.
In early March, the American CEO of CureVac, Daniel Menichella, joined the heads of other coronavirus vaccine developers in a meeting with President Donald Trump at the White House.
A little more than a week later, Menichella was out as CureVac's CEO and the German biotech was at the center of swirling rumors that the U.S. had sought to buy the company, or its research.
Seemingly in response, the German government invested 300 million euros in CureVac for a 23% stake. CureVac added another $500 million through private investments, an alliance with GlaxoSmithKline and an initial public offering in the U.S. Much of the proceeds are being used to develop its coronavirus shot.
CureVac's vaccine, which has also been funded by CEPI, uses messenger RNA to encode the coronavirus' spike protein, much like BioNTech's and Moderna's. Early tests showed the shot spurred an immune response against the SARS-CoV-2 virus.
Months passed before, on Dec. 14, CureVac said it was beginning a Phase 2b/3 trial that is set to enroll 36,500 volunteers in Europe and South America. The trial will test a two-dose regimen, spaced four weeks apart. Trial monitors will take early looks at the shot’s efficacy after 56 and 111 COVID-19 cases, CureVac said. A final analysis will occur after 185 cases.
How quickly those cases occur will depend on the level of virus spread where the trial is enrolling volunteers. Based on the current situation, CureVac anticipates it could have early data by the end of the first quarter, company CFO Pierre Kemula told BioPharma Dive.
Most recently, CureVac partnered with Bayer on further development and, should trials succeed, supply of its vaccine. The companies expect to manufacture about 300 million doses in 2021, and roughly double that thereafter. Some 400 million of them could go to the European Union under a proposed supply deal, and a 75 million euro loan from the European Commission is meant to expand production further.
Clover's candidate was the second protein-based vaccine to begin human testing for the new coronavirus, trailing only Maryland-based Novavax when its Phase 1 study began in mid-June.
Like the name suggests, protein-based vaccines are designed to expose the body's immune system to viral proteins. In the case of SARS-CoV-2, that's the spike protein which the virus uses to enter cells.
Protein-based vaccines are often paired with adjuvants, compounds that help boost the immune response to vaccination. Clover's trial is testing its candidate together with adjuvants developed by GlaxoSmithKline and Dynavax, potentially providing a proving ground for those companies' technologies in inoculating against SARS-CoV-2.
No detailed results are available yet, but Clover has reported data from 150 volunteers that showed the vaccine paired with either adjuvant was safe and capable of generating immune responses. A Phase 2/3 study testing the vaccine with GSK's adjuvant is expected to start in December, while one with Dyanvax's adjuvant is set to begin in the first half of 2021.
CEPI has provided Clover with additional financial muscle, pledging nearly $70 million in July to fund the Phase 1 study and prepare manufacturing capacity should the candidate succeed.
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 previously marked record speed but in the COVID-19 age appeared more deliberate.
The pharma sped up its plans, however, securing help from the U.S. government through Operation Warp Speed. An initial study began in late July and two months later, on Sept. 23, J&J kicked off a global Phase 3 study.
J&J had planned to recruit 60,000 volunteers, but reduced its enrollment target after cases of COVID-19 began to accelerate rapidly in the U.S. during the late fall. On Dec. 17, the drugmaker announced the study had been fully enrolled with approximately 45,000 participants.
Data should come by the end of January, J&J said, although that timeline could shorten if cases of COVID-19 in the trial occur faster than expected.
J&J is aiming to prove a one-shot regimen, a goal others have found challenging to achieve. Early study results published Jan. 13 in the New England Journal of Medicine showed that, by four weeks after one dose of the vaccine, nearly all trial participants had coronavirus antibodies circulating in their blood. A second, exploratory dose given to some volunteers did increase antibody levels, although it's not clear whether that would translate to greater rates of protection.
J&J did hit one speed bump, pausing vaccinations in mid-October across all ongoing studies, after a participant got sick with an unexplained illness. Less than two weeks later, an independent panel monitoring board recommended vaccinations resume, finding no evidence to connect J&J's vaccine with the volunteer's illness.
J&J expects to be able to supply 1 billion doses of its vaccine, beginning early next year, and figures to be an important partner for the U.S. and other governments.
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 used against influenza.
From the outset, it was clear that Sanofi and GSK wouldn't be among the first to complete testing. Their initial development timeline was months behind that of Moderna, Pfizer and even Novavax, which uses a similar technology.
The two companies hoped to make up for slower speed with a more potent vaccine than others, a view they attributed to their adjuvanted approach, which is meant to strengthen the body's immune response to vaccination.
In July, they locked in $2.1 billion in support from the U.S. government, more than any other developer besides Moderna, to back the effort.
But events have moved quickly since then. Pfizer and BioNTech, as well as Moderna, showed their vaccines to be about 95% effective against COVID-19, far better results than anticipated.
Sanofi and GSK's shot, by comparison, fell well short of expectations. Initial results from a Phase 1 study in December were so disappointing the two companies decided to advance an upgraded formulation of the vaccine, a major setback that could delay the program by as much as nine months.
A Phase 2b study of the new vaccine will start by February, with a late-stage trial following in the second half of 2021. Should those go well, initial availability could come by the fourth quarter.
Despite the delay, however, the companies' efforts could still be important, given the relative ease with which their vaccine can be shipped and stored and the number of countries depending on their progress. The U.S., U.K., Europe and Canada have pre-ordered hundreds of millions of doses.
Merck came late to the coronavirus vaccine race, having publicly announced its efforts near the end of May. Rather than bet on newer messenger RNA technologies, Merck homed in on approaches it believed would produce immunity quickly with one shot.
But Merck's delay, surprising for one of the world's top vaccine makers, wasn't entirely due to initial caution. The pharma initially sought to partner with the University of Oxford, developer of the vaccine candidate now licensed by AstraZeneca, but was turned down, The Wall Street Journal reported in October.
Left searching for partners, Merck in May instead opted to buy the privately held Austrian company Themis and its vaccine candidate, as well as license another from the nonprofit group IAVI.
A Phase 1/2 study of the Themis vaccine began in Belgium in early September, while a trial of the IAVI-developed shot got underway in November.
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, Daria Hazuda, its head of infectious disease discovery, told BioPharma Dive. The IAVI program is based on the same approach behind Ervebo, the company's approved Ebola vaccine.
The company had argued it could make up ground on its rivals later on, but the better-than-expected success from first Pfizer and then Moderna may now make that a tougher proposition.