More than half a dozen prospective coronavirus vaccines are now in Phase 3 trials, the last stage of efficacy testing before a vaccine can be fully deployed in the wider population. Below we profile in brief the developers and platforms the candidate vaccines use. This updates our earlier archived post about the most promising candidate vaccines and the platforms — from RNA to inactivated COVID viruses — that they use.
- In pre-clinical/Phase 1 trials, vaccine candidates are tested in animals and then small numbers of people to test safety and dosage.
- In Phase 2 trials, vaccines are given to larger groups of people to check immune stimulation and whether different groups (e.g. defined by sex, ethnicity or age) show different responses.
- In Phase 3 trials, vaccines are given to tens of thousands of people in an epidemic situation, with one large group getting the real thing and another a placebo. If the vaccine works, those given the placebo will be the only ones getting infected.
Experts have emphasized that transparency is crucial in terms of how vaccines are developed and tested, especially given that the latest polls show declining public trust in potential COVID vaccines — an extremely worrying sign if we are to get wide enough uptake of a vaccine to halt the pandemic.
The upshot: it seems likely that at least preliminary Phase 3 trial data will be available in late October, meaning that large-scale manufacturing of the lead candidate vaccines can begin. Our guess is that the first doses could be administered before the end of 2020 — quite an extraordinary result if it pans out, given that vaccines traditionally take over a decade to develop.
Perhaps the furthest along of all the major vaccine candidates, AstraZeneca’s prospective COVID-19 vaccine uses a weakened form of a common cold virus that usually infects chimpanzees. It is genetically altered to carry some of the code for key proteins in the SARS-CoV-2 virus, thereby eliciting a protective immune response in humans.
This vaccine is now in Phase 3 trials in the United Kingdom, Brazil, South Africa and the United States. The trials hit a roadblock in early September when it was disclosed that a UK recipient of the test vaccine had suffered an adverse event, though it is unclear whether this was due to chance or a response to the vaccine. The UK trial was briefly halted but is now underway again, though the US trial remains on hold.
Regarding the timing of Phase 3 trial results, AstraZeneca says: “Results from the late-stage trials are anticipated later this year, depending on the rate of infection within the clinical trial communities.” The company has already reached an agreement with the EU to supply 400 million doses of the vaccine on a no-profit basis. It adds that: “Recent supply announcements with Russia, South Korea, Japan, China, Latin America and Brazil take the global supply capacity towards three billion doses of the vaccine.”
This Chinese company has also produced a vaccine based on the human variant of the same adenovirus approach. While it has passed Phase 1 and 2 safety and efficacy tests, some see the decision to deploy it in Chinese soldiers before Phase 3 results are in as too rushed. A Phase 3 trial involving 40,000 participants (20,000 each for a placebo and the real thing) is now underway in Pakistan. A second Phase 3 trial — though with just 500 participants, so with limited statistical power — is underway in Russia.
This rapid pace — and the fact that the AstraZeneca trial has had to be halted for a time — means that CanSino may be the first company to produce a proven vaccine. According to Reuters, a Chinese CDC official has told state TV that a vaccine could be ready for the general public as early as November or December, though he didn’t say which vaccine (several efforts are underway in China). As is often the case in China, news is sketchy — CanSino has not released any official information on its COVID vaccine since March.
Russia’s ‘Sputnik V’
Russia, of course, already claims to have won the vaccine race. Launched as always with an eye to Soviet-style propaganda, the so-called Sputnik V vaccine hadn’t yet completed standard Phase 1 and 2 testing and Russia’s regulator later walked back on the announcement. The test results have since been published in the Lancet and look reassuring — the safety profile was good and a strong immune response was seen. However, some researchers have since raised questions about apparent duplications in the data and other concerns.
The vaccine is another adenovirus vector approach and is being developed by the Gamaleya Research Institute, part of Russia’s ministry of health. A 40,000-person Phase 3 trial is now underway in Russia.
Also in Phase 3 trials — with 30,000 people enrolled from the US, Argentina, Brazil and Turkey — this vaccine employs an entirely new technology, which uses mRNA to get human cells to produce immunogenic proteins in the body rather than injecting them from outside. On Sept. 12 the companies announced that they would be expanding Phase 3 trials to include 44,000 people. Phase 1 and 2 trials produced promising data, with the subsequent results reported in Nature in August.
With the pandemic currently picking up pace again, timing is everything. The companies recently released a statement: “As stated previously, based on current infection rates, the companies continue to expect that a conclusive readout on efficacy is likely by the end of October.”
Another mRNA platform in Phase 3 trials is Moderna’s mRNA-1273 candidate. This trial also involves the standard 30,000 participants, with with over 100 locations across the US currently recruiting healthy adults to take the prospective vaccine. Moderna, too, has faced bumps along the road, not least getting embroiled in a patent battle in July over some of its vaccine technology.
Moderna has announced a supply agreement with the US government for 100 million doses of its vaccine — at a cost of US$1.5 billion — as part of America’s “Operation Warp Speed,” with the option to purchase another 400 million doses. It has provided no details on the timing of any Phase 3 readout, but the medical news service Endpoints News currently puts Moderna at number two, behind BioNTech/Pfizer, in its “Covid-19 vaccine race” tracker.
Sinovac and Sinopharm
The remaining Phase 3 candidates are Chinese efforts using the older tried-and-tested method of inactivated viruses as a vaccine. Sinopharm is currently running a Phase 3 trial among 15,000 people in Abu Dhabi, while Sinovac is running a trial in 9,000 health care professionals in Brazil.
Reuters has reported that Sinovac’s coronavirus vaccine candidate, CoronaVac, has already been approved in China for emergency use in high-risk groups such as medical staff. In late July Sinopharm said its vaccine could be ready for public use by the end of 2020, though no further details have been provided.