The race intensifies for a COVID-19 vaccine as hope builds for emergency approval by September

As the COVID-19 pandemic continues to disrupt life as we know it, it is becoming clearer than ever that a safe and effective vaccine will be the only way we can go back to "normal". Even then, once this pandemic ends, we might emerge with a new "normal" as we are forced to remain vigilant and prepared for future outbreaks to avoid a repeat of the catastrophic impact this pandemic has had on communities, healthcare systems, and the economy.

With the world now looking to vaccines to effectively end the ongoing COVID-19 pandemic, the race to the finish line could be swifter - although less straightforward - than initially anticipated. There are seven COVID-19 vaccine candidates already in clinical testing and nearly 70 in the pipeline; however, a select few are currently leading the race, and are consequently benefiting from sizeable contributions from international charities, and governments that have pledged billions of dollars to not only expedite the development of promising vaccine candidates but to also manufacture millions of doses before any clinical data demonstrating safety and efficacy. Funding contributions by the Coalition for Epidemic Preparedness Innovations (CEPI) and the US government's Biomedical Advanced Research and Development Authority (BARDA) - which have each contributed nearly USD1 billion to support COVID-19 vaccine research so far - will help support at-risk production of promising candidates, allowing millions of people to get immunized quickly if any vaccine-candidates prove to be successful in clinical testing. The US' BARDA has so far announced sizeable funding support for Moderna (US)'s, Janssen (US)'s and Sanofi (France)'s vaccine candidates. CEPI is supporting eight COVID-19 vaccine development programmes including Moderna's vaccine candidate, as well as those being developed by Curevac (Germany), Inovio Pharmaceuticals (US), Novavax (US), the University of Hong Kong, the University of Oxford, the University of Queensland and a consortium led by Institut Pasteur.

Millions of doses for Oxford's vaccine candidate in at-risk production

The Serum Institute of India, the world's largest vaccine manufacturer, has recently announced that it will mass-produce around 5 million units per month of The Oxford Vaccine Group's investigational COVID-19 vaccine (hAdOx1 nCoV-19) ahead of any clinical data results and can scale up production to 10 million units per month to potentially have up to 40 million doses by October. The Oxford vaccine candidate only recently started clinical testing with a Phase I/II trial set to enroll 1,112 participants in the UK. However, regulators have already green-lighted an unprecedented regulatory timeline, boosted by favourable data from animal and primate studies (yet to be published), as well as previously reported safety data from clinical trials of similar vaccines for Ebola and Middle East respiratory syndrome (MERS). According to the New York Times, a Phase II/III trial for The Oxford Group's vaccine candidate is set to begin by next month, and will enroll another 5,000 participants, potentially months ahead of other candidates that have yet to complete animal studies.

AstraZeneca (UK) has also recently announced a landmark collaboration with the University of Oxford aiming to produce 100 million doses of the ChAdOx1 nCoV-19 vaccine, according to the Financial Times. Although the financial terms of the agreement were not disclosed, both partners have agreed to operate on a not-for-profit basis during the course of the pandemic.

Emergency Access to Vaccines by September

Although seven vaccine candidates have already launched into early-stage clinical testing, and others will be launching very soon, many have not yet completed animal studies that could rule out the risk of antibody-dependent enhancement (ADE), also referred to as vaccine-enhanced disease, before much larger trials can be initiated. ADE is considered a major safety hurdle in vaccine development whereby a vaccine could lead to an exacerbated illness or a worse outcome than would otherwise have been the case. The Oxford Group appears to have already passed that hurdle, suggesting that the stockpiles already being produced could quickly make their way to at-risk populations, such as healthcare workers or the elderly, under emergency use protocols. If it proves to be effective, millions of doses could be made available by September, according to the group. Sarah Gilbert, the Oxford University professor leading the research efforts on hAdOx1 nCoV-19, is optimistic that the vaccine candidate has an 80% chance of success and could be "ready by September". It remains to be seen whether the UK government will grant emergency approval for use in at-risk populations.

Meanwhile, the director of the Chinese Center for Disease Control and Prevention, Gao Fu, has announced that an unnamed COVID-19 vaccine could be developed and ready for emergency use by special groups in September 2020, with the rest of the population gaining access in early 2021. There are at least three vaccine programmes in China under clinical development, including ones by Sinovac, CanSino (China), and the Wuhan Institute.

Pfizer (US) and BioNTech (Germany)'s BNT162 vaccine candidates are also under clinical development and potentially not too far behind. Pfizer's Chief Scientific Officer, Mikael Dolsten, announcing on a call with investors that following initial data release, anticipated in May/June, the company would launch expanded trials that could support "emergency use or accelerated approval" potentially by October. The two companies have started to ramp up manufacturing capacity at risk to provide global access to a successful vaccine as soon as regulatory approval is granted. Millions of vaccine doses could be available by the end of 2020, and then capacity could be rapidly expanded to produce hundreds of millions of doses in 2021, according to Pfizer.

It is also worth noting that emergency approval does not equate to full regulatory approval. IHS Markit does not anticipate full approval of a vaccine before early 2021, with forecasts for sufficient mass production that could meet entire population demand coming a little later in 2022.

Many factors could impact vaccine access, including protectionist policies

While the Oxford group's vaccine appears to be one of the leading candidates currently in development, several factors could affect the candidate's availability timeline. First, as the COVID-19 outbreak winds down slowly in the UK, it is unclear whether researchers will be able to extract sufficient information regarding the vaccine's safety and efficacy by September or will need to rely on other trials in other outbreak areas. Second, any of the candidates could encounter unexpected hurdles during testing that could result in termination of development, including potential safety signals such as ADE or lackluster efficacy, that may only become apparent in late-stage testing. Third, although manufacturing capacity has already started ramping up at risk, billions of units will be needed to vaccinate the entire population of the planet in a timely and equitable manner. This may take a while, unless more collaboration agreements and more pledges to share resources are made.

The World Health Organization (WHO), CEPI, the European Commission, and other partners including the Bill & Melinda Gates Foundation (BMGF) have recently launched the Access to COVID-19 Tools (ACT) Accelerator, "a landmark, global and time-limited collaboration to accelerate the development, production and equitable global access to new COVID-19 essential health technologies." The global initiative will likely support greater relaxation of patent exclusivity rights on innovative products including treatments and vaccines and calls for unprecedented levels of cooperation through licensed-manufacturing deals. The US and China are notably absent from this initiative. In parallel to this concerted effort, the European Union along with its partners will be working on raising EUR7.5 billion in initial funding through a global pledging marathon for COVID-19 diagnostics, treatments and vaccines. According to European Commission President, Ursula von der Leyen, "We need to bring the world, its leaders and people together against coronavirus", adding "We need to develop a vaccine, to produce it and deploy it to every corner of the world. And we need to make it available at affordable prices."

Millions of units of the Oxford group vaccine candidate are being produced across Europe and India, facilitated by collaborations with pharmaceutical companies AstraZeneca (UK) and Merck KGaA (Germany) as well as contract manufacturing firms Halix BV (Netherlands), Advent (Italy), and Cobra Bio AB (Sweden/UK). The group has yet to reach a manufacturing agreement in North America, according to the New York Times, potentially because pharmaceutical manufacturers in the US would not be granted exclusive rights for investing in the candidate, thereby providing little financial incentive for companies. The Oxford group has confirmed they are not patenting the vaccine.

During a pandemic, would it be wise to ignore the significant benefits of a coordinated global effort to solve the world's biggest problem?

Posted 29 April 2020 by Margaret Labban, Ph.D., Life Sciences Senior Analyst