The vaccines that could stop Covid-19
When we’ll know if it works: December at the earliest and by May the latest, judging by the Phase III trial protocol the company released in mid-September. But Moderna executives have said that they could seek an emergency authorization from the FDA in November.
Canada’s health agency and the UK’s drug regulator have started reviewing the company’s vaccine data on a rolling basis.
Supply: In a Sept. 18 SEC filing, Moderna said it could produce approximately 20 million doses of the vaccine by the end of the year and between 500 million and one billion doses during 2021.
The U.S. has agreed to purchase 100 million doses for $1.5 billion, with an option to acquire 400 million more. Moderna has also inked deals with Canada, the European Union, and Switzerland.
The backstory: It took just 63 days from the time the company started designing its vaccine to launch the first clinical trial, a rapid pace made possible in part by Moderna’s use of genetic material called messenger RNA. When that mRNA is injected into a patient, it directs
cells to make a protein found on the coronavirus — and stimulates the production of antibodies.
No mRNA vaccine for any disease has yet won approval. But the FDA has given Moderna’s shot fast-track designation, and the Biomedical Advanced Research and Development Authority has pledged more than $950 million to accelerate its development.
CanSino Biologics and Beijing Institute of Biotechnology
Status: Authorized for China’s military, and Phase III trials ongoing. Pakistan and several Latin American countries are also discussing the potential for emergency authorization of the vaccine, according to the Wall Street Journal. The company is planning late-stage trials in various countries, hoping to enroll about 40,000 participants in Russia, Brazil, Chile and Saudi Arabia. Mexico said in early November that it received the first doses of the vaccine candidate for a Phase III trial of between 10,000 and 15,000 volunteers.
Supply: The company has not said how many doses it will produce annually, but Russia’s Petrovax, which is running a late-stage trial of the vaccine, said it will be able to produce more than 4 million doses of CanSino’s vaccine per month this year, and 10 million doses per month in 2021. CanSino will also supply 35 million doses to Mexico starting at the end of 2020.
The backstory: This experimental vaccine, developed in China, was created to combat Ebola. It uses an inactivated version of a virus that causes the common cold to carry a gene that causes cells to make a protein found on the coronavirus — with the goal of sparking an immune response.
The vaccine was the first in the world to move into Phase I testing, in March. Results from a phase II trial showed the vaccine was generally safe, but older study participants showed significantly weaker immune responses than younger participants. The responses also varied based on a population’s pre-existing immunity to the common cold virus that forms the vaccine’s base.
China’s Central Military Commission said in June that it would allow the military to give the vaccine to soldiers for one year.
In August, CanSino raised about $750 million with an initial public offering on a Chinese stock market.
Johnson & Johnson
Status: Phase III trial ongoing. 60,000 participants in 28 U.S. states, Argentina, Brazil, Chile, Colombia, Mexico, Peru, Philippines, South Africa and Ukraine receive a single dose of the vaccine or placebo. The company is also planning another clinical trial in 30,000 participants across Europe, South Africa, Philippines and Florida to test two doses of the vaccine.
When we’ll know if it works: Sometime in early 2021.
Supply: J&J is providing 100 million doses of its vaccine to the U.S. for about $1 billion, with the option to provide 300 million more doses. J&J also inked deals to provide 200 million doses to the EU, as well as the possibility for an additional 200 million doses, and 30 million doses to the U.K. Canada agreed to purchase 38 million doses of the vaccine. J&J also pledged 500 million doses for low-income countries, with deliveries beginning in mid-2021.
The South African company Aspen Pharmacare announced a deal in early November to manufacture the vaccine at its facility in Port Elizabeth, South Africa, which it said has the capacity to produce more than 300 million doses per year.
The backstory: Johnson & Johnson is working with the Biomedical Advanced Research and Development Authority, which provided $456 million in funding, and Boston-based Beth Israel Deaconess Medical Center on a single dose vaccine that uses an inactivated version of the common-cold virus to carry genetic material into cells. That material prompts the body to pump out proteins found in the coronavirus in the hopes of drawing an immune response.
The trial was set to restart at the end of October, after being briefly paused due to an unexplained illness in a study participant.
Pfizer and BioNTech
Status: Phase III trial ongoing.
The European Medicines Agency and Health Canada have started a review of the vaccine data as it comes in.
When we’ll know if it works: Early data released November 9 show the vaccine could be about 90 percent effective after a review of the first 94 infections in the Phase III trial.
Pfizer CEO Albert Bourla said he won’t apply for an emergency authorization before the third week of November while the company waits for more safety data. The Phase III trial launched on July 27 and seeks to enroll 44,000 participants from the U.S., Argentina, Brazil and Germany. More than 43,000 participants have been enrolled so far, and more than 37,000 participants have received both shots of the vaccine, as of early November.
Supply: The companies said they can manufacture up to 100 million doses by the end of 2020 and potentially more than 1 billion doses by the end of 2021. Pfizer said the U.S. should expect to receive its 100 million doses by March.
The U.S. government placed an initial order of 100 million doses of the vaccine for $1.95 billion and can acquire up to 500 million additional doses, if it proves successful in late-stage trials.
The companies also signed a binding agreement with the U.K. government in July to sell 30 million doses of the vaccine if it proves effective and another one with Japan to provide it with 120 million doses in the first half of 2021. Pfizer and the Canadian government in August also agreed for an undisclosed number of doses to be provided in 2021. Pfizer is in talks with the EU to supply 200 million doses, with an option for 100 million more doses. Chile signed a purchase agreement with the two companies for 10 million doses.
The backstory: The two companies — one American, one German — are partnering on an mRNA coronavirus vaccine. Pfizer is paying BioNTech $185 million upfront as part of the collaboration.
Preliminary results from the Phase I/II trial, released in July ahead of peer review, showed the vaccine elicited a strong immune response — including the production of the immune cells known as T cells. But Pfizer selected a different formulation of the vaccine for its final round of testing. The formulation that was selected, known as BNT162b2, also elicited a strong immune response in a Phase I study, the company reported in a pre-print publication in August, and may have a better safety profile than the other formulation, known as BNT162b1.
The FDA has already granted “fast track” designation to both.
The German government provided BioNTech with a grant of more than $440 million in September.
Sanofi and GlaxoSmithKline
Status: Phase I/II trial ongoing, with 440 healthy adults at 11 sites in the U.S. A Phase III trial could begin before the end of the year, the companies said.
When we’ll know if it works: Sometime in the first half of 2021.
Supply: Sanofi and GlaxoSmithKline in July inked an up to $2.1 billion deal with the U.S. government to further develop their vaccine and provide Americans with 100 million doses. The U.S. has the option to purchase another 500 million doses of the vaccine if it proves safe and effective.
The companies also signed agreements to supply 60 million doses of the vaccine to the U.K. and up to 72 million doses to Canada, beginning in 2021. The European Commission also struck a deal with Sanofi for 300 million doses to be provided to the 27 EU member countries. The two companies will also supply 200 million doses of the vaccine to COVAX, a global facility meant to provide vaccine access to the most at-risk groups all over the world at the same time.
The backstory: This experimental vaccine combines Sanofi technology that produces a protein found in the coronavirus, which aims to trigger an immune response, with an adjuvant made by GlaxoSmithKline designed to heighten that immune response.
University of Oxford and AstraZeneca
Status: Phase III trials ongoing in the U.S., U.K., South Africa, Brazil, Chile and Peru.
Globally, the company said that 23,000 have been enrolled in its trials as of early November.
The European Medicines Agency, the U.K. drug regulator and Health Canada have begun reviewing the vaccine data as it becomes available.
When we’ll know if it works: Possibly by the end of the year.
Supply: AstraZeneca said it has the capacity to deliver over two billion doses of the vaccine. The company signed a deal with the U.S. in May to make available at least 300 million doses and to help carry out the Phase III trial with 30,000 participants in the U.S., for about $1.2 billion.
The company is also expected to supply Japan with 120 million doses. In September, the Australian government said the University of Oxford/AstraZeneca and the University of Queensland/CSL will provide more than 84.8 million vaccine doses for the Australian population, with early access to 3.8 million doses in January and February 2021.
AstraZeneca and the European Commission have also signed a deal to supply EU member countries with 300 million doses of the vaccine, with an option for 100 million doses more. The U.K. has signed up for 100 million doses, but Kate Bingham, the chair of the country’s Vaccine Taskforce, said in November that AstraZeneca will likely only deliver 4 million doses by the end of the year. The Chilean government has said it had reserved 14.4 million doses of the vaccine, Reuters reported.
The backstory: The British university and drug company are teaming up on a vaccine that — like the CanSino Biologics candidate — is based on a weakened version of the common cold that contains some genetic material from the coronavirus.
The Phase I/II results, published in July, showed the vaccine provoked a strong immune response, with participants producing antibodies and more T cells. Oxford and AstraZeneca were able to launch large-scale trials quickly based on data from earlier safety tests of similar vaccines, including one last year designed to target a different coronavirus.
All of the late-stage trials were halted on September 8 after participants in a U.K. study developed unexplained neurological symptoms. The U.S. trial restarted on October 23, several weeks after the other trials restarted.
Sinovac
Status: Approved on an emergency basis in China, and Phase III trials ongoing worldwide.
The vaccine, known as CoronaVac, was approved in July for emergency use as part of a program in China to vaccinate medical staff and other high-risk groups.
Brazil’s drug regulator halted a Phase III trial for about 9,000 health care professionals the trial in November after a serious adverse reaction in a participant, the New York Times reported. Indonesia’s president said in July that his country will run a Phase III trial, which is expected to last through December. A trial is also underway in Chile. Other countries potentially running late-stage trials include Turkey and Bangladesh.
The company plans to run an early-stage trial in about 550 children and adolescents aged 3 to 17 in China.
When we’ll know if it works: The company CEO Yin Weidong said in late September that the vaccine should be ready for worldwide distribution by early 2021, including in the U.S., the Associated Press reported.
Supply: Sinovac has said that it is building manufacturing capacity to produce as many of 100 million doses of its vaccine. Indonesian company PT Bio Farma said it will produce at least 40 million doses of the vaccine before March 2021.
The Chilean government and the Chinese company have agreed the country would purchase 20 million doses as part of the agreement regarding the vaccine clinical trial in Chile, Reuters reported.
The backstory: The vaccine from China-based Sinovac is made of a purified, inactivated coronavirus and it uses an adjuvant from Dynavax, which the California company uses in its own Hepatitis B vaccine.
Phase II trial results showed the vaccine prompted the development of neutralizing antibodies in more than 90 percent of participants. The company said in September that the vaccine shows good safety and immunogenicity in healthy adults ages 60 and older from its Phase I/II trials conducted in China, which is comparable to the results seen in younger healthy adults.
Brazilian President Jair Bolsonaro said in October that he rejected the announced purchase of 46 million doses of the potential vaccine which is being tested in a state governed by a political rival, prompting some to question if he was allowing politics to steer public health decisions.
Novavax
Status: Phase III ongoing.
About 9,000 participants have been enrolled in the U.K.-based trial as of early November, out of the 15,000 participants between the ages of 18 and 84 targeted.
Another Phase III trial with 30,000 participants in the U.S. and Mexico will begin by the end of November.
When we’ll know if it works: Sometime in early 2021.
Supply: The U.S. government awarded Novavax $1.6 billion in early July to conduct a late-stage trial and ramp up its manufacturing capability — enough to deliver up to 100 million doses by year’s end. Novavax gets $800 million of that award immediately. The government will determine before December whether the company, which has never brought a product to market, gets the other $800 million.
Similar to Pfizer’s vaccine, the FDA granted the Novavax vaccine fast-track designation.
Novavax is also slated to sell the U.K. 60 million doses of its vaccine, with some to be manufactured in the U.K. by Fujifilm Diosynth Biotechnologies. The Serum Institute of India said in September that it will manufacture about one billion doses of the vaccine in 2021. Canada agreed to purchase 76 million doses of the vaccine. The European Commission is also set to enter negotiations with the company for doses, according to a POLITICO Europe report. Takeda will manufacture over 250 million doses per year of the vaccine.
The backstory: The company’s vaccine consists of coronavirus proteins that are encased in nanoparticles, plus a chemical known as an adjuvant that helps enhance the body’s immune response to the shot.
The results from the Phase I safety study, which enrolled 131 people, showed that the vaccine provoked an immune response without major side effects. Those who received a version of the vaccine containing an adjuvant produced a high level of antibodies with relatively mild side effects, the company said in early findings released in August ahead of peer review.
The same month, Novavax announced the beginning of a Phase IIb clinical trial in South Africa to evaluate the efficacy of the vaccine candidate, which is supported in part by a $15 million grant from the Bill & Melinda Gates Foundation. The trial is ongoing and planned to enroll 2,665 healthy adults in one cohort, and about 240 medically stable, HIV-positive adults in another.
Novavax is also running a trial with up to 1,500 healthy volunteers, with approximately half of them older than 60, at up to 40 sites in Australia and the U.S. The trial is supported by funding from the Coalition for Epidemic Preparedness Innovations.
Inovio
Status: Phase II/III on hold until the company can answer some FDA questions that were not disclosed publicly. The company said it plans to respond to FDA this month, and the regulator will then have up to 30 days to notify Inovio of its decision. Inovio also said the partial clinical hold is not due to the occurrence of any adverse events in an earlier Phase I trial.
Supply: At peak capacity, contract manufacturer Thermo Fisher projects that it could produce at least 100 million doses of Inovio’s vaccine annually.
The backstory: The Pennsylvania biotech company’s vaccine uses DNA that prompts cells to produce the spike protein the coronavirus uses to attack the body. The idea is that those proteins — harmless when detached from the rest of the virus — will prompt a strong immune response.
Inovio reported in late June that its vaccine provoked an immune response in 94 percent of the 40 people enrolled in a Phase I trial. The vaccine is also in Phase I/II trials in South Korea and China. The company initially expected to launch a Phase II/III trial later this summer, but later said that it will begin in September. It has received funding from the Bill and Melinda Gates Foundation and the Coalition for Epidemic Preparedness Innovations, which has also backed vaccines from Moderna and others.
Operation Warp Speed — the U.S. government’s vaccine and drug accelerator — had selected Inovio’s experimental vaccine for a primate study comparing the shot to others in development. The company said its vaccine was effective in protecting monkeys from the virus 13 weeks after the last vaccination.
Sinopharm
Status: Authorized in China, the United Arab Emirates and Bahrain for front-line health workers. The company has two vaccines in ongoing Phase III trials.
A Phase III trial in Abu Dhabi completed enrollment with 15,000 volunteers in August and is expected to be done until the latest January. A late-stage trial in the UAE has enrolled 31,000 participants.
Peru, Morocco, Jordan, Bahrain and Brazil have also approved or are planning to run Phase III clinical trials for the vaccine candidates.
Supply: The company built a new vaccine manufacturing plant in July in Wuhan, China — where the coronavirus first emerged — and expects to produce more than 200 million doses per year there.
The backstory: The company is using an inactivated coronavirus in two of its vaccines, which have backing from the Chinese government.
Early data published in the Journal of the American Medical Association in August showed the one of the vaccine candidates, administered as two and three doses in the Phase I trial, provoked an immune response and was generally safe.
Vaxart
Status: Phase I trial ongoing.
The company said in October that it vaccinated the first people in Phase I, open-label, dose-ranging study that will be conducted in up to 48 healthy adults aged 18 to 54 years old. Enrollment is expected to be completed by early November. The study’s primary objective is to examine the safety and reactogenicity of two doses of the vaccine.
The backstory: The company is developing an oral tablet vaccine, and said in late June that it would be tested in monkeys in a trial organized and funded by the U.S. government’s Operation Warp Speed vaccine accelerator.
The company has since disclosed that it was served with a Grand Jury subpoena from the U.S. District Court for the Northern District of California, in connection with an investigation by the Office of the U.S. Attorney for the Northern District of California because of the way it disclosed its involvement with Operation Warp Speed.
Results from the company’s early-phase trial in hamsters exposed to the virus showed that all hamsters that received two oral doses of the vaccine candidate showed no systemic weight loss, which the company said is “a key indicator of protection against COVID-19 in this animal model.”
Vaxart has never brought a product to market, and its vaccine candidate has not been tested in people.
Merck
Status: Phase I/II trial ongoing for one of two different vaccines.
One of the vaccines in development, known as V591, which Merck is working on together with subsidiary Themis, is enrolling about 250 volunteers and began in mid-September in Belgium. Data from the trial is expected by the end of the year.
Merck’s other vaccine, developed with the nonprofit research organization IAVI, is expected to begin a Phase I trial in about 250 healthy participants in late October.
The backstory: V591 is a vaccine candidate that uses a measles virus vector platform.
The second one, based on the IAVI collaboration, uses a recombinant vesicular stomatitis virus technology, which was the basis for the company’s FDA-approved Ebola vaccine.
Merck and IAVI have received $38 million from BARDA to develop this vaccine.
Sputnik V
Status: Authorized in Russia, and Phase III trials ongoing. Russia submitted the vaccine candidate to the World Health Organization for prequalification in late October.
Russia’s drug regulator approved the vaccine developed by the state-owned Gamaleya Research Institute on August 11, after limited testing in humans. It has begun a local Phase III aiming to enroll 40,000 participants. Clinical trials also are expected or are ongoing in the United Arab Emirates, the Philippines, Belarus, Saudi Arabia, China, Mexico and Hungary.
Supply: Russia expects to be able to produce between 1.5 million and 2 million doses per month by the end of the year, according to RIA news agency.
Kirill Dmitriev, head of Russia’s sovereign wealth fund, said on August 11 that Russia had already received foreign requests for one billion doses, with agreements secured to produce 500 million doses annually.
Dmitriev said Vietnam’s Ministry of Health has applied to purchase 50 to 150 million doses of it. Indian drugmaker Dr. Reddy’s said in mid-September that it will cooperate with Russia’s sovereign wealth fund on clinical trials and distribution of the vaccine in India. Dr. Reddy’s will receive 100 million doses of it upon approval from the Indian regulators. Argentina agreed to buy 25 million doses of the vaccine if it proves successful in clinical trials.
The backstory: The vaccine is reportedly a mixture of two adenovirus vectors, but since it has not undergone Phase III trials, it’s unlikely to win approval from European or U.S. regulators yet.
Results published in the Lancet in September from two early-phase, non-randomized trials in a total of 76 people showed the vaccine appears to be safe and can elicit broad immune responses.
Russia plans to publish interim results based on the first 42 days of monitoring volunteers from its Phase III trial this month, according to Reuters.
The Russian drug regulator approved a second coronavirus vaccine in mid-October, known as EpiVacCorona, prior to the completion of late-stage trials.
CureVac
Status: Phase I/II trials ongoing.
The company in late September began a Phase IIa trial in Peru and Panama to confirm the dose of the vaccine in 690 healthy volunteers.
In early November, CureVac reported positive interim data from its ongoing Phase I study of 250 healthy individuals, showing the vaccine to be safe and that it can provoke an immune response.
CureVac is expected to proceed to a Phase IIb/III clinical trial before the end of the year and will enroll about 30,000 adults from Europe, Latin America, Africa, and Asia.
Supply: The EU is in talks to purchase 225 million doses of the vaccine.
The backstory: Similar to Pfizer and Moderna, Germany-based CureVac is developing an mRNA vaccine candidate. A Phase I safety trial for the candidate began in June in Germany and Belgium and tested a range of doses.
In June, the German government invested €300 million ($356 million) in the company, acquiring a 23 percent stake. In early September, CureVac said it would receive up to €252 million ($298 million) in support for the vaccine candidate from the German Federal Ministry of Education and Research. GlaxoSmithKline in July took an equity investment in CureVac of about $178 million, representing close to a 10 percent stake, in addition to an upfront cash payment of about $142 million.
CureVac in August raised another $210 million in a U.S. stock market listing, which is expected to help pay for the vaccine candidate’s later clinical trials.
