SARS-CoV-2 Vaccines Inch Towards Regulatory Approval
Over the past month or so, investigators have been amassing data on SARS-CoV-2 candidate vaccines as quickly as possible and some of that data is making its way — ever so much more slowly — through regulatory agencies for official scrutiny.
Quite possibly the fastest data review will be for AstraZeneca and the University of Oxford’s AZD1222 vaccine in Britain, where the Medicines and Healthcare Products Regulatory Agency is now conducting a “rolling review” of the vaccine in an effort to speed up the approval process. Canada launched its own rolling review of the same vaccine in October of this year.
In a rolling review, regulators are allowed to see data in “real time” and communicate with vaccine makers on issues such as manufacturing in order to accelerate the process. AstraZeneca was forced to halt its Phase III trial temporarily in September as one of the trial participants developed a rare, but serious, reaction following receipt of its vaccine. The trial has now resumed and the company has already pledged to supply some three billion doses of its vaccine to governments around the world in anticipation that it will gain speedy regulatory approval.
Meanwhile, Johnson & Johnson’s COVID-19 vaccine suffered a similar fate and it, too, had to temporarily halt its 60,000-patient trial due to an unexplained illness in a study participant. The trial was subsequently set to resume after the company’s review of the episode found no connection between the illness and its vaccine. Pfizer has also confirmed that it will be seeking emergency authorization of its vaccine against SARS-CoV-2 by the third week in November, provided it is found effective. Apparently, review of the safety data will take longer.
The US-based biotech company, Moderna, in turn, isn’t far behind everyone else, having hit its own enrolment target of 30,000 participants who are ready to receive the company’s candidate vaccine. Moderna has also announced that they should have sufficient safety data on their vaccine before Thanksgiving in the US. If a vaccine is authorized for use, the US will reportedly have enough doses to immunize 100 million people with at least one dose.
Regulators are actually not setting a very high bar to approve any vaccine, requiring only that it be at least 50 percent effective against the virus and that there are at least two months of follow-up on half of the study participants in any vaccine trial.
Even Canada is now getting into the SARS-CoV-2 vaccine act. The Canadian federal government recently announced that they now have a deal to manufacture some 76 million doses of a vaccine being developed by Medicago, a Quebec City-based biotechnology company to whom the feds have promised $173 million to help them get started on their own COVID-19 clinical trial. The company is planning to do its first round of clinical testing in Quebec, but it will undoubtedly have to go outside of the country to attract a bigger pool of volunteers as testing proceeds.
Canada is also planning to test an old vaccine against tuberculosis (TB), known as the Bacille Calmette-Guerin (BCG) vaccine. While no longer routinely used in Canada because the incidence of TB is too low in the country to justify its use, there is some evidence that widespread vaccination against TB in countries such as India may explain why the death rate from COVID-19 in India is low compared to European countries, where BCG immunization is not routine either.
The Canadian trial, which has already been launched, will evaluate whether volunteers who receive the BCG vaccine are less prone to infections in general, including infection with SARS-CoV-2. If the theory holds, the BCG vaccine represents a safe, inexpensive and, most importantly, already-approved vaccine for potential use against COVID-19.
Vaccine Nationalism and Vaccine Hesitancy Pose Threats to Public Health
No matter how close the front-runners appear to be getting to a viable SARS-CoV-2 vaccine, a report from Duke University’s Global Health Innovation Center predicted that there will not be enough vaccines (and yes, that is plural, as the world needs more than one vaccine against COVID-19 to cover the world’s population) until 2024.
This is in part because high-income countries have practiced a militant kind of “vaccine nationalism,” securing a large supply of multiple vaccines for their own citizens and leaving low- and middle-income countries to fend for themselves. The Duke University report also found that Canada has secured far more vaccine doses per person than any other country.
Ironically, Canada is the second-largest contributor to a global initiative known as the COVAX Facility whose aim is to ensure all countries — rich and poor — have equal access to a vaccine when one finally becomes available. Then there is the real specter of vaccine hesitancy. According to a recent poll, a growing number of Americans say they are not likely to get vaccinated against SARS-CoV-2 even if a vaccine does become available within the foreseeable future.
For example, the percentage of white Americans who indicated that they were likely to get a COVID-19 vaccine dropped from 70 percent to 59 percent between mid-August and early October, while the percentage of Black Americans who said they were likely to get a vaccine dropped from 65 percent to 43 percent. It could turn out that the true wild card in the race to protect the world against the coronavirus are people themselves.
Meanwhile, there is still power in social distancing measures when it comes to limiting the spread of this endless pandemic. According to a simulation model, the timing of the introduction of — and easing off from — social distancing measures had a pronounced effect on the burden of COVID-19 infections in the US.
For example, by bringing in social distancing measures one week earlier in New York City, researchers estimated the number of COVID-19 infections could have been reduced by 80 percent by the end of May 2020. In contrast, a week’s delay in the implementation of the same distancing measures was estimated to have increased the number of COVID-19 cases by almost seven-fold at the same point in May.
The social distancing measures included in the simulation model included population density, the number of daily contacts among residents in the absence of social distancing and different levels of adherence to these measures.
COVID-19 Treatment Advances Mixed
Over the same month, advances in treatments for patients at risk for, or who are already infected with, COVID-19 were small and had largely mixed results. British researchers have now forged ahead with plans for the first human challenge trials with the Imperial College London announcing they will start infecting young volunteers early next year in the hopes of speeding up the development of a SARS-CoV-2 vaccine. Human challenge trials involve infecting volunteers with the virus only a few weeks after they have been vaccinated, which shortens the time needed to determine if a vaccine is effective.
Chile announced they plan on testing the drug interferon β as a potential therapy for COVID-19. So far, the drug has had mixed results in the treatment of COVID-19. However, researchers in Chile, Canada and Australia are set to launch a trial in which interferon β will be given prophylactically to members of a household where one of the other members has tested positive for the virus.
Members of the household will receive a total of three doses of the drug, the first within 72 hours of a family member testing positive and two more doses to cover the interval during which infection would be expected to take hold. The goal is to reduce viral shedding and make the virus less infectious to others.
Another WHO-led study into the Gilead Sciences drug, Veklury (remdesivir), already approved for treatment of COVID-19 in the United Kingdom and Europe, did not support previous positive results where remdesivir was found to shorten recovery time by an average of five days.
In the WHO study, approximately 2,750 patients received treatment with remdesivir while others received either interferon, the anti-HIV drug combination lopinavir-ritonavir, hydroxychloroquine or just usual care. Although results have not yet been published, investigators reported on an online site that remdesivir had no meaningful impact on survival. The WHO study, however, has been criticized for being poorly designed, which makes any conclusions reached questionable.
And other somewhat conflicting findings were also released from several studies evaluating Roche’s interleukin-6 (IL-6) inhibitor, Actemra (tocilizumab) in the treatment of coronavirus infection. In a large observational trial involving approximately 4,000 patients, those who received the IL-6 inhibitor within 48 hours of being admitted to the ICU were less likely to die than those who did not receive tocilizumab, with mortality rates of 28 percent versus 37 percent, respectively.
However, in another randomized trial carried out in Italy, results from 60 patients who received the drug and 63 who did not found that the same treatment did not benefit patients who were receiving oxygen, although they did not require ICU care in that particular study. A second randomized trial carried out in France involved similar numbers of patients who had moderate-to-severe COVID-19, but they did not require mechanical ventilation. At day 28, there was no difference in mortality between those who received treatment with the IL-6 inhibitor and those who did not.
Investigators say mixed results may be explained by when the drug is given — ideally before irreversible organ damage has occurred — and disease severity.