The urgent public health crisis created by the novel coronavirus has led to an unprecedented effort by researchers to create a vaccine, said experts at the Association for Value-Based Cancer Care’s final summer webinar on COVID-19 and cancer care, which was held August 27. “What we are trying to do has never been done before,” said Kevin Russell, MD, Executive Director, Clinical Research Vaccines, Merck Research Laboratories. “In the last 25 years, there have only been 7 truly new vaccines developed globally and approved for distribution. That includes 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.”
Because COVID-19 is a respiratory pathogen, it results in 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 added.
Challenges in Vaccine Manufacturing and Distribution
Dr Russell noted that there may be as many as 230 companies involved in some level of vaccine development for COVID-19, using a variety of strategies, including DNA- and mRNA-based vaccines, protein-based vaccines, and live attenuated vaccines. As of the time of the webinar, he said that for all of these vaccine candidates, the only results that have been publicly released are immunogenicity findings. “We need to get to efficacy data with the end points of infection or disease,” Dr Russell said. (In late September, new information was released by Johnson & Johnson about their vaccine, which introduced a different mechanism of action not addressed in this article.) If 1 or more of the vaccine candidates prove successful, what are the prospects for the manufacturing and distribution of the vaccine? “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 1 billion plus in capacity for the following years,” said Umer Raffat, MS, Senior Managing Director, Evercore ISI.
Mr Raffat is closely monitoring all of the vaccines with publicly available clinical data, including top players Moderna and Pfizer (mRNA vaccines), AstraZeneca and Oxford (a recombinant viral vector vaccine using a weakened virus), and Novavax (prefusion protein), all of which have begun phase 3 clinical trials.
However, the gap between where manufacturers want to be, and where they are now is quite large, Dr Russell noted.
“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 the inability to enroll people who have taken those vaccines into subsequent trials,” he explained.
“Distribution will represent a Herculean effort of global proportions,” said Patrick M. Schmidt, Chief Executive Officer and Founder, 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,” Mr Schmidt advised.
Dr Russell explained 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,” he said.
Public Concern Remains an Issue
There are also issues regarding public confidence in the vaccines currently being developed. Mr Raffat reported that in a survey of more than 1000 industry investors and company executives, virtually all said that they would wait at least 6 months to take a novel vaccine.
“Even these people in the biotech and pharmaceutical space don’t want to be first,” he pointed out. “Part of the challenge is that among our lead candidates include 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,” he said.
Cold chain distribution poses yet another challenge. “If a vaccine needs to be cryofrozen at –20°C, and is only stable for a few hours after thawing, as we’re hearing with the mRNA candidate, that suggests issues such as a shortage of refrigerated trailers,” said Mr Schmidt.
A realistic timeline for the first vaccine approval, or at least emergency use authorization, and early distribution, remains to be seen. Various public announcements have been made, but no reliable information has been released at the time of this publication.
“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,” Mr Raffat noted.