COVID-19 Vaccine Rollout Accelerates: A Panoramic Tracking of the R&D Pipeline

Editor's note: BioPharma Dive tracked COVID-19 vaccine development through this tracker from June 2020 to fall 2021. This article was last updated on November 24 and is now outdated; please consider it a historical record of COVID-19 vaccine development as of that time.

Over the past 18 months, scientists, pharmaceutical companies, and governments have advanced the development and production of COVID-19 vaccines at an unprecedented pace. The most advanced candidate vaccines have proven to provide strong protection against COVID-19. More than a dozen vaccines from the United States, the United Kingdom, Germany, China, India, and Russia have received regulatory approval from agencies worldwide.

This achievement is a scientific feat with few precedents. Never before has a vaccine been developed in such a short time, let alone been made ready for large-scale use and scaled up for production.

Given the threat to public health, governments have invested substantial funds in vaccine development and prepared for the production and distribution of the billions of doses needed to curb the pandemic. The ongoing immunization campaigns will help determine whether the virus will evolve into a recurring epidemic or eventually be brought under control. However, approved vaccines remain in short supply globally, and access largely depends on commercial agreements between pharmaceutical companies and wealthy nations.

Overview of leading vaccine candidates

The following is an overview of the most advanced, promising, or well-funded vaccine candidates as of November 24, 2021. Details for each developer are below.

Moderna

Vaccine type:Messenger RNA (mRNA) — delivers genetic instructions encoding the coronavirus spike protein encapsulated in lipid nanoparticles.

Target supply:700 million to 800 million doses in 2021, up to 3 billion doses in 2022, in partnership with Lonza.

External funding:Up to $5.96 billion (with undisclosed additional amounts).

A key advantage of mRNA technology is that, compared to traditional methods, pharmaceutical approaches that use genetic instructions to direct cells to produce proteins allow for simpler vaccine construction. Moderna's vaccine is an example: it went from computer design in January 2020 to human studies in just three months, making Moderna the first U.S. company to reach that milestone.

Phase 1 results were announced in late May, and mid-stage trials were initiated. The Phase 3 study began on July 27, and four months later yielded strongly positive results, showing the vaccine was94%effective at preventing COVID-19. Combined with the95%efficacy data reported by Pfizer and BioNTech in November, researchers were able to confirm the effectiveness of mRNA vaccines.

The company submitted a request for Emergency Use Authorization (EUA) to the U.S. Food and Drug Administration (FDA) on November 30, received advisory committee support on December 17, and the FDA authorized it the next day — a milestone for both the U.S. public health response and the decade-old biotechnology company. Initial supply was limited, but the company and its partners quickly ramped up production. On June 16, the U.S. government placed an additional order for 200 million doses, bringing total orders to 500 million doses. The company originally expected to deliver 800 million to 1 billion doses in 2021, but lowered its forecast in early November due to shipping delays and production challenges.

Large quantities of doses flowed to the United States and other developed countries, drawing criticism against Moderna. In late October, the company announced it would supply up to 116.5 million doses to low-income countries, nearly doubling its previous agreement with the vaccine alliance Gavi. Moderna also plans to invest $500 million to build an mRNA factory in Africa.

In the United States and Europe, the focus has shifted to booster shots. On August 12, the FDA expanded authorization to allow a third dose of the Moderna or Pfizer vaccine for people with weakened immune systems. Moderna submitted data in September showing antibody levels had "significantly" declined after six months, while a third dose could substantially boost antibodies. On October 14, an FDA advisory committee unanimously recommended authorizing a Moderna booster for the same groups as the Pfizer booster: adults aged 65 and older and younger people at high risk due to health conditions or occupation. The FDA approved days later. However, the committee voted against using the Moderna booster for the general population aged 18 and older.

Moderna is also seeking to expand use of the vaccine to younger age groups. A study in adolescents showed strong protection, and trials in children aged 6 months to 12 years are ongoing. However, in early November, the company said the FDA needed more time to assess a risk of heart inflammation, potentially delaying authorization for adolescents until early next year. On November 19, the FDA authorized a third dose of the Moderna vaccine for all adults aged 18 and older, in parallel with a similar authorization for the Pfizer/BioNTech vaccine.

CanSino Biologics

Vaccine type:Non-replicating viral vector — delivers the DNA sequence for the coronavirus spike protein via an adenovirus type 5 vector.

Target supply:Undisclosed.

External funding:Undisclosed.

CanSino was among the first to start human trials, report early data, and begin vaccinations outside of clinical studies. But these milestones have faded as the company struggled to complete large Phase 3 trials and obtain the evidence needed for regulatory approval outside China. Early and mid-stage trial results were sufficient to convince the Chinese military to authorize emergency use among soldiers last summer. The decline in cases in China prompted CanSino and other Chinese vaccine developers to seek trial sites overseas.

A large late-stage study enrolled volunteers in South America, Mexico, Pakistan, and Russia. On February 24, 2021, CanSino reported the single-dose vaccine was65%effective at preventing symptomatic cases 28 days after vaccination, and90%effective at preventing severe disease. The next day, Chinese regulators granted conditional approval. Results have not yet been published. Mexico and Pakistan approved it in February, Hungary in March, and Chile in April. On March 23, the company announced approval to conduct clinical trials of an inhaled version of the vaccine in China. Reuters reported in June that the vaccine was also being tested as a booster.

However, CanSino's chosen vaccine design may limit its potential. Early studies showed that pre-existing immunity to the adenovirus vector appeared to weaken the vaccine's effectiveness.

Inovio

Vaccine type:DNA — delivers a DNA plasmid encoding the coronavirus spike protein via electroporation.

Target supply:100 million doses in 2021.

External funding:$83 million (plus an additional $17 million).

Inovio fell behind in testing its COVID-19 vaccine after a rapid start. Due to the lack of a large pharmaceutical partner and relatively limited financial support, the company struggled to advance clinical trials of its candidate. Pooled data from a small Phase 1 trial were released in June 2020 and published in a medical journal on December 24. Vaccination was safe and elicited an antiviral immune response, but the response appeared weaker than that reported by Pfizer and Moderna.

The FDA placed a partial clinical hold in late September last year and did not allow the Phase 2 trial to begin until mid-November. Initial results from that study were released in May 2021. Inovio's candidate uses DNA to induce cells to produce the coronavirus protein, with electroporation (a process using tiny electrical pulses to open pores in cells) to allow the DNA molecules to enter cells. The device used was part of the FDA's concerns, and the company plans to address them through the Phase 2 trial.

Inovio originally planned to start a Phase 3 trial in the United States once the issues were resolved. But in April, the government withdrew funding for the program because other vaccines were available, and the company changed its plans. Two months later, Inovio announced a Phase 3 trial in partnership with Suzhou Abogen Biosciences. After another delay, Brazilian health authorities approved late-stage studies in Latin America, Asia, and Africa in late August. In early November, the FDA lifted the partial clinical hold, and Inovio was finally allowed to enroll participants in a Phase 3 trial in the United States. However, with three vaccines widely available, enrolling a large number of participants in the U.S. is unlikely. Even if the trial succeeds, Inovio may face a longer regulatory path as the FDA shifts its focus from emergency use authorization to full approval.

Sinovac

Vaccine type:Inactivated virus — SARS-CoV-2 is isolated, amplified, and then chemically treated to render it non-infectious.

Target supply:2 billion doses per year.

External funding:Undisclosed.

In the United States and Europe, vaccine developers bet on newer technologies such as mRNA or viral vectors. Sinovac, along with several companies and institutions in China and India, used the established inactivated virus vaccine approach and advanced almost as quickly. These vaccines (used for hepatitis A, influenza, and rabies) consist of viruses inactivated by heat or strong chemicals.

Sinovac was not the first to start, but it obtained late-stage trial results faster than several closely watched Western pharmaceutical companies. Preliminary reports from Brazilian study data showed strong efficacy, but subsequent announcements placed overall efficacy at just over50%— barely above the threshold set by global regulators. Brazilian researchers said the higher figure only counted COVID-19 cases requiring medical attention; when comparing protection against any severity, the number was lower. Incomplete disclosures added to confusion about Sinovac's vaccine, especially as researchers in Turkey and Indonesia reported different results.

The data were sufficient for Sinovac to receive conditional approval in China on February 8. On June 4, China extended authorization to children and adolescents. The vaccine has also been authorized for emergency use in 26 countries, including Indonesia, Brazil, Turkey, and Chile. The World Health Organization granted emergency authorization on June 1. However, recent reports have raised concerns about the vaccine's effectiveness, as countries heavily reliant on Sinovac and other Chinese vaccines report rising cases.

In July, researchers published interim results from a Turkish trial involving over 10,000 participants aged 18 to 59 who received two doses. Data published in The Lancet showed the vaccine was83.5%effective against symptomatic COVID-19. However, the researchers acknowledged the need for more testing, noting the "follow-up period was short, and participants were relatively young and low-risk." The study was also conducted before more concerning variants emerged in the summer of 2021. Earlier in 2021, the company claimed it had built capacity for up to 2 billion doses per year and had delivered 200 million doses globally. Sinovac is listed on Nasdaq, but trading in its stock has been suspended since February 2019 — due to a dispute with activist investors over control of the company.

BioNTech, Pfizer

Vaccine type:Messenger RNA (mRNA) — delivers genetic instructions encoding the coronavirus spike protein via lipid nanoparticles.

Target supply:3 billion doses in 2021, up to 4 billion doses in 2022.

External funding:$5.9 billion (plus an additional $445 million).

Moderna was not the only biotechnology company aggressively pursuing messenger RNA technology. In Mainz, Germany, BioNTech began work on an mRNA COVID-19 vaccine early and agreed to partner with Pfizer in March 2020, even joining forces before legal teams had finalized the contract. The partnership was historic: the two companies received approval from UK regulators just eight months later, followed by authorization in Canada on December 9 and FDA emergency use authorization on December 11. On August 23, the vaccine became the first COVID-19 vaccine in the United States to receive standard approval.

Unlike Moderna and other frontrunners, Pfizer and BioNTech initially advanced four slightly different prototypes before selecting one for late-stage trials. The Phase 2/3 trial began on July 28 and enrolled about 44,000 volunteers within three months. Data showed the vaccine was95%effective at preventing COVID-19, exceeding expectations. The vaccine then showed strong efficacy in a study of adolescents aged 12 to 15, and the FDA authorized its use in that age group on May 10. On November 22, the two companies disclosed updated results intended to support full approval.

Results in children aged 5 to 11 were released in September, showing the vaccine was safe and elicited antiviral antibodies in children. Pfizer submitted the data and applied for emergency use authorization in October. An FDA advisory committee voted on October 26 to recommend broad authorization, and the FDA approved three days later. As with the Moderna vaccine, the spread of viral variants, especially the highly contagious Delta variant, has raised questions about the durability of the vaccine's efficacy. On July 21, a UK study published in the New England Journal of Medicine found that two doses...