Coronavirus vaccines are rolling out quickly. Here's where the pipeline stands.
Editor's note: BioPharma Dive tracked COVID-19 vaccine development via this tracker from June 2020 through fall 2021. This story was last updated Nov. 24 and is now out of date. Please consider this a history of COVID-19 vaccine development up through that point.
Scientists, drugmakers and governments have moved with unprecedented speed over the past 18 months to develop and manufacture vaccines for the coronavirus.
The fastest of them have proven their vaccines can strongly protect against COVID-19. A dozen shots from developers in the U.S., U.K., Germany, China, India and Russia are cleared by regulators around the world.
Estimates of vaccine efficacy from Phase 3 clinical trials, primary series
Their success is a scientific feat with few parallels. No vaccine has ever been developed so quickly before, never mind readied for widespread use and manufactured at scale.
With the health of their citizens at stake, governments invested enormous sums of money into vaccine research and development, and to prepare to make and distribute the billions of doses necessary to curb the pandemic.
The immunization campaigns that are now underway will help determine whether the virus becomes endemic, recurring year after year, or is ultimately checked. Doses of authorized vaccines remain in short supply worldwide, however, and access has largely been dictated by lucrative deals struck between drugmakers and wealthy countries.
Vaccine frontrunners have progressed quickly
Here's where things stand for 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 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 2020 to human study in just three months, making Moderna the first U.S. company to reach that point.
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.
The finding was a dramatic achievement. Taken together with a similarly positive readout from Pfizer and BioNTech, which in November said their shot was 95% effective in preventing COVID-19, researchers could be sure that mRNA vaccines worked.
The company 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 were limited, although the company and its partners quickly ramped up production. On June 16, the U.S. contracted to buy another 200 million doses from Moderna, bringing its total order to 500 million.
The company had expected to deliver between 800 million and 1 billion doses in 2021, but in early November scaled back its forecast due to shipment delays and production challenges.
Many of those doses have gone to the U.S. and other developed countries, a fact that's led to significant criticism of Moderna. In late October, the biotech announced plans to supply up to 116.5 million doses to low-income countries, nearly doubling the size of an earlier deal with the vaccine alliance Gavi.
Moderna aims to expand in Africa as well, with plans to invest $500 million in an mRNA plant there.
In the U.S. and Europe, the focus has shifted toward booster doses of Moderna's and others' vaccines.
On Aug. 12, the FDA expanded its authorization to allow people with weakened immune systems to receive a third dose of the Moderna or Pfizer vaccines. Moderna sought wider clearance of boosters in the fall, submitting in September results showing antibody levels waned “significantly” after six months and that a third shot elevated them much higher. On Oct. 14, advisers to the FDA unanimously recommended authorization of Moderna’s booster dose for the same groups already eligible to receive an additional Pfizer shot: adults over 65, as well as younger people at higher risk of COVID-19 due to medical conditions or their job. The regulator followed days later with an authorization.
The committee opposed the approval of Moderna’s booster for the general population over 18, however.
Moderna could soon expand the use of its vaccine into younger groups as well. The shot was shown to be strongly protective in a study in adolescents, and a trial in kids six months to 12 years old is underway. But in early November, the company said the FDA would need more time to assess the risk of a type of heart inflammation, likely delaying a potential authorization in younger teenagers until early next year.
On Nov. 19, the FDA authorized a third dose of Moderna's vaccine for all adults over 18, a decision made in conjunction with a similar authorization for Pfizer and BioNTech's shot.
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 faded as the company 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 last summer. 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, originally intended to study its shot in Canada, but an agreement there came undone.
A large late-stage study is recruited volunteers in South America, Mexico, Pakistan and Russia. On Feb. 24, 2021, Cansino reported its vaccine was 65% effective in preventing symptomatic cases and 90% efficacy in preventing severe disease 28 days after a single shot. One day later, China's drug regulatory issued a conditional market authorization. The results have not been published.
Mexico and Pakistan approved the vaccine in February, Hungary authorized it in March and Chile followed in April.
On March 23, the company announced it secured clearance to begin a clinical trial of an inhaled version of the vaccine in China. Reuters reported in June that the CanSino vaccine is also being tested as a booster shot.
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.
After quickly launching development efforts, Inovio fell behind in testing its coronavirus vaccine. Lacking a large pharma partners and with comparatively little financial backing, the company has struggled to move its candidate through clinical trial stages.
Summary data from a small Phase 1 trial were disclosed by the company in June 2020, 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 was reported for Pfizer's and Moderna's shots, however.
A partial clinical hold imposed by the FDA in late September last year kept the company from conducting further study of its vaccine candidate until mid-November, when the agency cleared a Phase 2 trial to begin.
Preliminary results from that study were released by the company in May 2021.
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.
Inovio planned to launch a Phase 3 trial in the U.S. once those questions were resolved. But in April, the company changed its plans for that study when the government, citing the availability of other vaccines, pulled funding for the project.
Two months later, Inovio announced it would work with partner Advaccine Biopharmaceuticals Suzhou to run a Phase 3 trial. After another delay, the company was finally cleared by Brazil’s health agency in late August to begin a late-stage study in Latin America, Asia and Africa.
In early November, Inovio finally won clearance from the FDA to proceed with recruiting participants in the U.S. into its Phase 3 trial, after the agency lifted its partial clinical hold. With three vaccines widely available, though, enrolling significant numbers of people in the U.S. is unlikely.
And even if the trial is successful, Inovio may face a longer regulatory path as the FDA shifts to considering vaccines for full approval, rather than emergency authorization.
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 had reported differing results.
The data was good enough for Sinovac to gain conditional approval in China on Feb. 8, though. China expanded its authorization to include children and adolescents on June 4. The vaccine also has been authorized for emergency use in 26 countries, including Indonesia, Brazil, Turkey and Chile. The WHO gave the vaccine emergency authorization on June 1.
Recent reports, however, have raised concerns about the vaccine’s efficacy against COVID-19, as countries that relied heavily on shots from Sinovac and other Chinese drugmakers report rising cases.
Researchers in July announced interim results from the trial in Turkey, in which over 10,000 participants aged 18 to 59 received two doses. Data published in The Lancet showed vaccination resulted in 83.5% efficacy against symptomatic COVID-19 cases. However, researchers conceded more testing is needed, pointing out “a short follow-up period, relatively young, low-risk participants.” The study also took place before the emergence of more worrying virus variants in the summer of 2021.
Earlier in 2021, the drugmaker claimed it had brought online enough production capacity to manufacture up to 2 billion doses a year, and said it had already delivered 200 million doses globally.
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 March 2020, 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. On Aug. 23, the vaccine became the first coronavirus shot to win a standard approval in the U.S.
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 showed a better-than-expected 95% efficacy in preventing COVID-19.
The shot was later shown to be strongly effective in a study of 12- to 15-year-olds too and, on May 10, the FDA authorized its use in that age group. On Nov. 22, Pfizer and BioNTech disclosed updated results that they intend to use to support a full approval.
Results in 5- to 11-year-olds came in September, showing that in children, too, the vaccine was safe and spurred virus-fighting antibodies. Pfizer submitted the study's data to the FDA and applied for an emergency use authorization in October.
The agency's advisory committee voted on Oct. 26 in support of broad authorization, and an OK from the FDA quickly followed three days later.
As with Moderna’s vaccine, the spread of virus variants, most notably the highly contagious delta variant, raised questions about whether the Pfizer and BioNTech vaccine would remain as strongly effective. On July 21, a study out of the U.K., published in the New England Journal of Medicine, found two doses of the Pfizer vaccine still offered 88% protection against symptomatic disease caused by delta.
Pfizer and BioNTech started pushing the U.S. government for a booster shot earlier in the summer, starting a Phase 3 study for a third shot in July and formally submitting an application to the agency based on Phase 1 data in late August. The company announced in October that study results showed a booster shot restored strong protection against COVID-19, marking the most substantial clinical evidence in support of the additional dose to date.
The FDA said on August 13 it would allow certain people with suppressed immune systems to receive a third dose of the Moderna or Pfizer vaccine. The Biden administration announced plans soon after to roll out booster shots broadly, but was forced to narrow those plans after the FDA on Sept. 22 authorized use only in older adults, those with underlying health conditions and those who work or live in high-risk settings.
On Nov. 19, the FDA authorized a booster dose of Pfizer and BioNTech's vaccine for all adults over 18 years old, while simultaneously granting a similar clearance to Moderna's shot.
Pfizer and BioNTech have contracted to supply the U.S. with 600 million doses, announcing on July 23 that the U.S. government purchased an additional 200 million doses to be delivered from October 2021 through April 2022. The government reached that number in late October with the final purchase of 50 million doses for children. With the EU, meanwhile, the companies recently agreed to supply up to 1.8 billion doses through 2023. The companies are on track to produce nearly 3 billion doses in 2021, according to the BioNTech CEO.
Lucrative supply deals like those with the U.S. and Europe have resulted in a sales windfall for both companies. Pfizer currently expects $36 billion in revenue from the shot this year, a historically large sum equivalent to about 80% of its expected 2021 sales across the rest of its business.
When Chinese scientists made the new coronavirus' genetic sequence available in January 2020, 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 last April, had started a large Phase 1 trial.
AstraZeneca signed on to help soon after, 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 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. Trials in other countries resumed quickly, but the U.S. trial didn't reopen until Oct. 23.
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.
Despite the confusion, the U.K. drugs regulator authorized the shot about a month late. The European Medicines Agency followed in late January with a conditional authorization. The agency's decision was shadowed, however, by a conflict between the two parties over supply, after AstraZeneca told the EU it would deliver fewer doses than originally planned.
In early 2021, more than 20 European nations temporarily paused immunizations over dozens of reports of abnormal blood clots and low platelet counts in younger vaccine recipients. On April 7, the EMA confirmed a possible link between vaccination and the events, recommending they be added to the shot's labeling as a very rare side effect. Some European countries later restricted the shot’s use to older age groups or advised younger recipients to get another vaccine. The U.K.’s vaccine safety committee, for instance, on May 7 advised people under 40 to get a different shot.
A U.K. study published in the New England Journal of Medicine showed two shots of the AstraZeneca vaccine were 67% effective against the delta variant and 74.5% effective against the alpha variant, which emerged in the U.K.
In the U.S., AstraZeneca initially said it would file for an emergency authorization, following positive results from a large trial there. However, the filing took longer than originally anticipated, reportedly because of the large amount of real-world data going into AstraZeneca's application. On July 29, the company confirmed the change in plans, announcing it would seek a standard U.S. approval by the end of the year.
The British drugmaker is also searching for a new manufacturing partner in the U.S. after the federal government directed a contractor to only make a vaccine from Johnson & Johnson's vaccine after a production mix-up at a key Baltimore factory.
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.
While the Western world focused on leading candidates from large multinational drugmakers, China's state-owned Sinopharm advanced two inactivated vaccines through late-stage trials and to approvals in more than a dozen countries worldwide.
Early-stage studies began last 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 2020.
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. On May 18, the country announced it would offer a third dose as a booster shot to people who received the first two doses, citing concerns of the vaccine’s efficacy. Bahrain made a similar announcement on June 3.
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 now authorized in more than 30 countries. The WHO is has also endorsed the shot.
Sinopharm's other shot was developed by another unit of the company, the Wuhan Institute of Biological Products, and was 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, can now claim success after winning authorization of its COVID-19 shot in Indonesia on Nov. 1. But the Maryland-based biotech is having difficulties mass producing its vaccine, and consequential regulatory reviews in the U.S., Europe and other countries remain ongoing.
In mid-June, the Maryland-based biotech reported results from a nearly 30,000-volunteer study run in the U.S. and Mexico, results from which had been anticipated for weeks. Data showed the company’s vaccine was 90% effective in preventing COVID-19, a strong result that confirmed findings from an earlier test in the U.K.
The results positioned Novavax to ask for regulatory approval. However, Novavax still needs to finish its manufacturing process and the company’s production scale-up has hit delays. The company disclosed in a quarterly filing that the U.S. federal government will no longer fund production of its vaccine until it resolves these manufacturing setbacks.
The vaccine’s protection against coronavirus variants first detected in South Africa and in India is also a question mark. A smaller, mid-stage study in the former country found the shot’s efficacy was much weaker, about 49%, and there were few cases of the latter variant in the large Phase 3 study run in the U.S. and Mexico.
Novavax's work has gained broad financial support. By the end of last May, the company had won a large grant from the nonprofit Coalition for Epidemic Preparedness Innovations and started an initial clinical trial, boosting its shares nearly 9-fold in the process. In July 2020, 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.
With a growing share of the U.S. adult population vaccinated, however, it’s unlikely many of those doses get used in the U.S., if the shot is authorized by the FDA. On August 5, Novavax announced it asked regulators in India, Indonesia and the Philippines to allow emergency use of its vaccine and, on Sept. 23, filed for emergency use listing with the World Health Organization, too. An application for U.K. clearance followed on Oct. 27.
The company said in September that it also planned to submit applications to the EU, Australia and Canada “within the next couple of months,” pushing back an earlier timeline.
Its application for emergency authorization in the U.S., however, now won’t be filed until the fourth quarter, rather than before the end of September as the company had previously expected.
The company is one of the largest suppliers for the international vaccine alliance COVAX having finalized a deal in May to begin delivering an expected 1.1 billion doses in the third quarter.
But Novavax has already faced manufacturing and regulatory setbacks, hindering its potential impact. In late July, for instance, The Guardian reported an order of 51 million doses for Australia and expected this year won’t arrive until 2022. An October report from POLITICO, meanwhile, indicated production problems involved difficulties in maintaining the purity of doses through manufacturing.
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 a significant example of how the race to develop a coronavirus vaccine came to be quickly 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.
With help from Russia's government and sovereign wealth fund, Gamaleya 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. Researchers calculated efficacy against COVID-19 as more than 91% and the data were published two months later in The Lancet.
Gamaleya also agreed to work 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. The trial began at the end of February.
More than 60 countries have authorized GRI's shot, although only some have begun vaccinations. A number have agreed to manufacture it as well, including the Serum Institute of India, which announced its cooperation with the Russian Direct Investment fund in mid-July. SII said they expect to start producing GRI’s vaccine in September with a goal of manufacturing over 300 million doses in India per year.
In late April, however, regulators in Brazil rejected importing the vaccine over concerns the virus used to deliver it was not appropriately inactivated. The backers of Gamaleya's vaccine criticized the decision, calling it "of a political nature."
Earlier in 2021, Gamaleya researchers had started a trial in which participants received only one dose of the vaccine. In May, Russia announced a single shot was 79.4% effective, but did not publish the results. The country granted authorization for use on the same day. A study in Argentina, which was released on June 2, found its effectiveness was between 78.6% and 83.7%.
In early March last year, 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.
But on June 16, the company announced interim results from a large, late-stage study of some 40,000 volunteers that showed its vaccine was only 47% effective at preventing COVID-19, much lower than other shots and below the bar for regulatory clearance. CureVac's final estimate, announced on June 30, hardly changed, coming in at 48%.
CureVac executives attributed the disappointing outcome to the "unprecedented" spread of coronavirus variants in the areas where it was testing the shot. But other factors, such as differences in the design of the vaccine, could have impacted efficacy, too.
After the results were announced, CureVac said it still planned to seek regulatory approval in Europe, arguing that its vaccine could play an important role as variants become more prevalent.
In mid-September, CureVac announced it was scaling back its manufacturing in Europe, attributing the downsizing to "reduced short-term peak demand for vaccines following the first wave of the pandemic vaccination efforts" and "corresponding changes in the demand of its first-generation COVID-19 vaccine candidate." On Oct. 12, the company terminated the development of its mRNA vaccine altogether, saying it withdrew its application in Europe and would instead focus its efforts on another coronavirus vaccine in development with partner GlaxoSmithKline. Recently announced data from animal testing suggest the new design could improve on the first version.
CureVac expects clinical development of its second-generation candidate to begin in early 2022.
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 chose to test its candidate together with adjuvants developed by GlaxoSmithKline and Dynavax, and planned to study both in mid- to late-stage studies.
On Feb. 1, however, Clover announced it would only proceed with a trial of its vaccine and Dynavax's adjuvant, which the companies started on March 24. The partnership with GSK, Clover said, was discontinued and the planned study dropped.
The decision was unexpected, particularly as Clover had said early testing results showed both adjuvants to be safe and capable of raising an immune response.
In September, data from a Phase 3 study of Clover’s vaccine with Dynavax’s adjuvant showed it was 67% effective at preventing symptomatic COVID-19. Against the delta variant, which has fueled much of COVID-19's resurgence in the U.S. and elsewhere, the vaccine was 79% effective against symptomatic disease.
The results could mean another vaccine option becomes available in the near future, potentially helping the many nations that have to obtain sufficient supplies of the shots currently available. The company previously agreed to sell more than 400 million doses to the vaccine alliance GAVI for global distribution.
CEPI has provided Clover with financial muscle, pledging nearly $70 million in July to fund the Phase 1 study and prepare manufacturing capacity should the candidate succeed. The group will fund the Phase 2/3 trial and, on Feb. 1, extended a roughly $100 million forgivable loan to begin "at-risk" manufacture of the vaccine.
In November, Clover completed the process of listing as a public company on the Hong Kong stock exchange, raising about $240 million.
Medicago and GlaxoSmithKline began working together on a vaccine candidate last July. The pair combined the plant-based technology of Quebec City-based Medicago with an immune-boosting adjuvant from GSK.
While the companies fell short of their original goal to complete development and make the vaccine available in the first half of 2021, the shot has advanced faster than a higher-profile candidate GSK is developing with Sanofi.
GSK and Medicago disclosed Phase 1 results in November 2020. All 180 subjects, male and female ages 18-55, had an immune response to vaccination after two doses.
Phase 2 data confirmed those early findings, showing vaccination increased neutralizing antibody levels to 10 times what researchers observed in blood samples from recovered COVID-19 patients.
Younger adults responded more strongly than older adults did after one dose, researchers said, but that difference narrowed after the second dose, given 21 days later.
In March, the companies received approval from Canadian and U.S. regulators to begin enrolling healthy adults in a Phase 3 trial. The study is currently underway with sites in Canada, the U.S., the U.K. and Brazil. The companies aim to enroll up to 30,000 subjects, making for a similarly sized trial as those conducted by Moderna, AstraZeneca and several others.
Medicago’s plant-derived vaccine candidate, which uses plants as bioreactors to produce a non-infectious particle mimicking the coronavirus’ spike, is one of only a handful of its type in clinical testing. The company used the same technology to develop an influenza vaccine, which is currently under review by Canadian health authorities.
Medicago has reached an agreement with the Canadian government to supply up to 76 million doses of its vaccine. The company also has a large-scale factory in Quebec currently under construction. Once completed in 2023, it will have the capacity to produce more than 1 billion doses of vaccines per year, according to Medicago. GSK, meanwhile, last May set a target to manufacture one billion doses of its adjuvant in 2021 to support various vaccine candidates.
Medicago’s vaccine is being funded, in part, by the Canadian government, which gave the company an unspecified amount of the $192 million available for projects as part of its COVID-19 Response Fund. The government of Quebec also awarded 7 million Canadian dollars, or about $5 million, to the company’s vaccine efforts.
J&J was first among larger drugmakers to pursue a coronavirus vaccine, announcing in January 2020 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 2020, 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.
In January 2021, data from that study showed a single dose of J&J's vaccine was 66% effective in preventing moderate or severe COVID-19. Efficacy was higher among participants recruited in the U.S., but lower in volunteers in Latin American and South Africa, where more virulent variants of SARS-CoV-2 were prevalent.
Still, the company's shot has advantages, as it can be given via one injection and shipped at normal refrigerator temperatures. On Feb. 27, the U.S. FDA granted it emergency authorization, making J&J's vaccine the third available in the country. European regulators followed with a conditional authorization on March 11.
Reports of cases involving dangerous blood clots near the brain combined with low platelet counts prompted the FDA and CDC to recommend pausing use of J&J’s shot on April 13. J&J said it will delay the vaccine's rollout in Europe as a result.
The cases were few — only a handful out of millions of doses given. But the symptoms were similar to a side effect linked to AstraZeneca’s vaccine, which uses a similar technology, adding to regulators' concerns.
Nonetheless, a CDC panel on April 23 voted that the benefit of protecting against COVID-19 outweighed the risk of the rare side effect, and didn't restrict the vaccine's use in any age group. The FDA quickly cleared vaccinations to continue with updated labeling to the shot's prescribing information.
In July, J&J released new data suggesting their single shot could hold up against the fast-spreading Delta variant. This new data also showed that immune responses to the vaccine lasted through at least eight months.
The same month, however, the FDA added a new warning over the very rare risk of Guillan-Barre, which had been reported in about 100 people of the roughly 12.5 million vaccinated with J&J’s shot by then.
As public health officials grew concerned about the risk of breakthrough infections over the summer, there was little guidance for recipients of J&J’s vaccine about whether they remained sufficiently protected. In late September, however, data from another large Phase 3 study showed a second shot, given two months after the first, could increase efficacy against COVID-19, potentially opening the door for an additional, or booster, dose to be given.
The company formally applied for FDA authorization of an additional dose in early October and received a green light from the agency on Oct. 20. A CDC panel affirmed the FDA’s decision a day later. The expanded authorization opened J&J recipients over 18 years to receive a booster dose at least two months after their first shot.
The clearance from both the agencies also allowed for mixing booster doses. Health officials believe an mRNA booster could be particularly beneficial, after a study from the National Institutes of Health indicated J&J recipients might have a stronger immune response if they receive an extra dose of an mRNA vaccine.
J&J expects to be able to supply 1 billion doses of its vaccine, with 200 million set to go to the U.S. Europe bought 200 million doses as well, an order Catalent is helping to fill by reserving two production lines at a plant in Italy for J&J's shot.
In the U.S., the Biden administration helped to broker a deal involving Merck & Co., which agreed to help J&J make its vaccine and fill vials for shipping.
But production hit a setback in March and April, when a costly take over oversight of the factory, run by Emergent Biosolutions.
In early June 2021, the FDA agreed some doses from the facility could be used, but recommended roughly 60 million more be thrown out due to possible contamination.
Sanofi and GlaxoSmithKline agreed to join forces last April, 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 used 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 to back the effort.
But Sanofi and GSK's shot 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 began in February, and read out positive results in mid-May. Sanofi and GSK said their redesigned shot resulted in immune responses equivalent to what researchers have observed following COVID-19 infections. Importantly, the vaccine's safety profile appeared to be better than the previous version.
The companies plan to start a Phase 3 study in the coming weeks and aim to have results 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. So has COVAX, an international alliance aiming to equitably distribute shots to poorer nations and economies.
In March, Sanofi began testing an mRNA vaccine it has been developing with Translate Bio, starting a Phase 1/2 trial that the companies expect to deliver results by the third quarter this year. In late September, the company announced it would suspend development of its mRNA coronavirus vaccine, citing the availability of Pfizer’s and Moderna’s despite what it claimed were positive results. Sanofi said it plans on using mRNA technology in an influenza vaccine instead and targeted clinical testing to begin in 2022.
GSK, meanwhile, has begun a Phase 3 study of a protein-based shot with its other vaccine development partner, Medicago.
Merck arrived late to the coronavirus vaccine race, publicly announcing 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 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.
The company had argued it could make up ground on its rivals, but weaker-than-expected results from early tests led Merck to scrap development of both candidates in late January — a surprising and significant setback. Immune responses generated by both vaccines were comparatively less than what's been observed following natural infections as well as in testing of other experimental shots.
Instead, Merck said it will focus its resources on developing COVID-19 treatments, including an antiviral pill being developed with Ridgeback Biotherapeutics. In October, the companies announced the drug, called molnupiravir, lowered the risk of hospitalization and death by roughly 50%. With these positive results, Merck said it plans to seek emergency authorization for the pill in the U.S. "as soon as possible" and will also apply for clearance in other countries.
In February, the company agreed to help make J&J's vaccine and fill vials for shipping, an unusual collaboration between large drugmakers that was brokered by the Biden administration.