More than 180 different vaccine candidates based on a variety of technological approaches are in development, The Milliken Institute reported in June. At least four have now advanced candidates to Phase 3 efficacy trials, and about a dozen more have entered early stages of human testing.
The overarching goal: to respond to the raging COVID-19 pandemic by shrinking vaccine development from the traditional 5-7 years effort to less than 12 months.
Several international experts have named the vaccine created by Oxford University scientists and licensed to AstraZeneca as the current leader. AstraZeneca is conducting multiple large-scale Phase 3 trials of this candidate, AZD1222, which includes a protein from the SARS CoV-2 virus strain, with testing sites in the United Kingdom, United States, Brazil and South Africa. The company expects a preliminary data readout from at least one of these Phase 3 trials by September, with all trials to complete by year end. If the early results are positive, AstraZeneca expects to receive emergency authorization for its vaccine by fall, with more general availability of the product possible in the first half of 2021. The AstraZeneca/Oxford vaccine was shown in a Phase 1 trial to elicit both an antibody and a T-cell response, which some experts believe will be needed for lasting protection. AstraZeneca CEO Pascal Soriot says he expects this first vaccine to provide protection for a year, comparable to current influenza vaccines.
Moderna, which we cited as leading the pack in May, also advanced its mRNA vaccine into Phase 3 trials in late July with a similar goal of providing a vaccine for emergency use by fall. Results from a Phase 1 study reported the successful generation of high levels of neutralizing antibodies against the virus after two doses of the vaccine.
Vaccine candidates from the Chinese firms Sinovac and Sinopharm are also in Phase 3 testing. Both are based on inactivated whole viruses, an older technology that has been used to create influenza and other vaccines. A third Chinese vaccine, developed by CanSino, was granted limited authorization for use with the country’s military, although its reportedly limited efficacy and severe side effects have discouraged its commercial licensure and development for a broader market.
Nations have been racing with funding for development and manufacturing to secure vaccines for their populations. In the United States, Operation Warp Speed is a multi-agency effort that aims to make a coronavirus vaccine available by the end of 2020. Officials have declined to reveal the full list of development programs that have received funding to date, but AstraZeneca received $1.2 billion in May for AZD1222 and NovaVax received $1.6 billion in June for its vaccine, which uses a protein from the SARS-CoV2 viral antigen. Moderna has also received $955 million from other U.S. governmental granting institutions as of August 5. Other countries are also offering significant funding: France is financially supporting Sanofi’s vaccine efforts, including manufacturing; Germany and the European Bank have provided CureVac with hundreds of millions of Euros for development; the United Kingdom, Brazil and the Serum Institute in India have all provided funding to AstraZeneca; and the United Kingdom is expected to soon complete large financing agreements with GlaxoSmithKline and Sanofi for 60 million doses.
While several of the vaccine developers have said they expect to have a product for emergency use before the end of 2020, the EMA and many US experts estimate it will take until mid-2021 before a vaccine is approved and available for more widespread use. The task of manufacturing enough doses to meet general population needs will be a significant challenge, and several groups, including Medicago, are already engaged in manufacturing scale-up and building production facilities even before an actual vaccine is at hand.
Parallel Race to More Effective Treatments
Given the expected delays before a first-generation vaccine is available, a parallel race is underway to develop and secure access to new, potentially game-changing therapeutics that could help reduce the effects and prevent the worst outcomes of COVID-19 infection.
Gilead received U.S. emergency authorization for its antiviral remdesivir in May. Since then, Gilead’s drug has also received conditional approvals in Europe and Australia, while a generic version developed by Mylan has been conditionally approved for use in India. Gilead’s clinical studies with remdesivir initially showed the drug to reduce hospital stays by four days, and data presented in July suggests its ability to reduce the risk of dying by 62%. Researchers also presented new data in July clearly demonstrating the drug’s ability to halt replication of the SARS-CoV-2 virus in human and animal lung cells. Based on this new data, Gilead has begun clinical trials of an inhaled form of remdesivir, which – if safe and effective – could be used to treat patients at home, at an earlier stage of the disease.
Another important advance was the clinical discovery in June that dexamethasone, an inexpensive, widely used steroid, could reduce deaths by a third in severely ill COVID-19 patients on ventilation and by a fifth in those receiving supplemental oxygen in other ways.
Further studies are ongoing in the United States, Europe and elsewhere with a variety of repurposed and potential new therapeutics. Among the latter are several antibody-based drugs designed to halt the coronavirus. The National Institute of Allergy and Infectious Diseases (NIAID) and other NIH institutes have launched several clinical studies to evaluate monoclonal antibody therapeutics in outpatients, as well as in hospitalized adults. Monoclonal antibodies capable of treating COVID-19 patients are also the focus of development programs by Regeneron/ Vir and Eli Lilly/ AbCellera, with clinical studies evaluating their product candidates in both outpatient and hospital settings.
Regeneron has also teamed with NIAID on a Phase 3 prevention study in the United States, Brazil, Mexico and Chile, which aims to treat 2,000 uninfected people with close exposure to confirmed COVID-19 patients. Operation Warp Speed is helping to speed Regeneron’s efforts with $450 million in funding for large-scale manufacturing, with the goal of getting a drug onto the market in as little as two months should clinical trials be successful.