The urgent international push to develop a vaccine for the novel coronavirus represents an unprecedented effort, said experts during the final summer Association for Value-Based Cancer Care webinar on COVID-19 and the Cancer Care Ecosystem, which was held August 27 and focused on the development of a vaccine.
“What we are trying to do has never been done before,” said Kevin Russell, MD, Executive Director of Clinical Research Vaccines for Merck Research Laboratories. “In the last 25 years, there have only been 7 truly new vaccines developed globally and approved for distribution. That is all manufacturers worldwide. It generally takes more than 10 years to develop a new vaccine, and only about 6% of vaccine efforts are ultimately successful.”
The fact that COVID-19 is a respiratory pathogen makes it an even more challenging target, Dr Russell said. “Think of the flu vaccine as an example; we know that respiratory viruses are more difficult to create lasting immunity. Nonetheless, I am optimistic about our ability to develop a preventive vaccine for COVID.”
He noted that some counts have as many as 230 companies involved in some level of vaccine development for COVID, employing a variety of strategies, including DNA- and mRNA-based vaccines, protein-based vaccines, and live attenuated vaccines. For all these vaccine candidates, at present the only results that have been publicly released are immunogenicity findings, Dr Russell said. “We need to get to efficacy data with the end points of infection or disease.”
Assuming that one or more of the vaccine candidates proves successful, what are the prospects for manufacture and distribution?
“If you look at the capacity commitments by most companies, the 5 leading players have committed to 1.7 billion doses by 2021, and have each talked about a billion-plus in capacity for the following years,” said Umer Raffat, Senior Managing Director for Evercore ISI, who is closely tracking all of the vaccines with publicly available clinical data, including top players Moderna and Pfizer (mRNA vaccines), AstraZeneca/Oxford (a recombinant viral vector vaccine using a weakened version of a chimpanzee common-cold virus), and Novavax (prefusion protein), all of which have begun, or are about to begin, phase 3 clinical trials.
But the gap between where manufacturers want to be and where they are now is quite large, Dr Russell said. “Manufacturing in vaccines is very challenging, and we don’t know what the immunogenicity, neutralizing antibodies, and T-cell data mean clinically without efficacy data. Every vaccine construct has its own challenges. And while we definitely need multiple vaccines, once the first vaccines start to be distributed, it will become more and more difficult to conduct trials of the others because of inability to enroll people who have taken those vaccines into subsequent trials.”
Distribution will represent a Herculean effort of global proportions, said Patrick Schmidt, CEO of FFF Enterprises, a leading supplier of critical care biopharmaceuticals, plasma products, and vaccines. “We can expect about 10 million to 20 million doses distributed in the first 2 months, with McKesson tapped for initial distribution by the federal government. There will be many challenges and we need to encourage patience.”
Dr Russell noted that the picture will become even more complicated as time goes on. “The FDA wants us to follow efficacy for up to 2 years, so the antibodies we see in the first few months are not what we’re going to see a year later, which is important in terms of determining whether boosters are needed.”
In addition, there is the question of public willingness to take a new vaccine. Mr Raffat reported that in a survey of industry investors and company executives—more than 1000 in total—virtually all said they would wait at least 6 months to get a novel vaccine. “Even these people in the biotech and pharmaceutical space don’t want to be first,” he said. “Part of the challenge is that among our lead candidates is an RNA vaccine, which is a platform that has never been dosed in humans, and a chimpanzee virus, which has not been used in humans in a commercial setting.”
Cold chain distribution poses yet another challenge. “If a vaccine needs to be cryofrozen at –20 Celsius and is only stable for a few hours after thawing, as we’re hearing with the mRNA candidate, that suggests issues such as shortages of refrigerated trailers,” said Mr Schmidt.
What is the realistic timeline for the first vaccine approval—or at least emergency use authorization—and early distribution? “I’m hearing feedback that AstraZeneca has shared in investor meetings regarding a 10,000-person ongoing phase 1 trial with accrued events, suggesting it’s not inconceivable that they will have early data to show by September,” Mr Raffat said. “Moderna/Pfizer seems to have a high level of confidence, but they haven’t yet entered into the window of measuring events. For Oxford/AstraZeneca, my sense is that they are already measuring events and their body language is positive.”