Date: 17th November 2020
COVID-19 vaccines are likely to be the most effective weapon against SARS-CoV-2, and the world is eagerly awaiting the imminent results of several Phase 3 clinical trials. Yesterday, Moderna announced the first interim analysis for the Phase 3 study of its candidate COVID-19 vaccine, mRNA-1273, has met the statistical criteria pre-specified in the study protocol for efficacy, with a vaccine efficacy of 94.5%.
We reported the start of the Phase 3 COVE study for mRNA-1273 at the end of July, and it has now recruited more than 30,000 participants in the US in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), and the Biomedical Advanced Research and Development Authority (BARDA). Participants have received 2 doses of the vaccine, and now, an external and independent committee has evaluated 95 confirmed cases of COVID-19 in trial participants.
Vaccine efficacy rate of just under 95%
The primary endpoint of the study, assessed at 2 weeks following the second dose of the vaccine, consisted of 90 cases of COVID-19 in the placebo group versus 5 cases observed in the mRNA-1273 group, resulting in a point estimate of vaccine efficacy of 94.5%.
The committee reviewed the safety data for the study, and reported no significant safety concerns. The majority of adverse events were mild or moderate in severity, and were short-lived.
The study also contained a secondary endpoint which included severe cases of COVID-19. Eleven severe cases were included in this first interim analysis, all of which occurred in the placebo group.
Based on these encouraging, positive data, Moderna intends to apply for an Emergence Use of Authorisation (EUA) with the US Food and Drug Administration (FDA) in the coming weeks once the final safety and efficacy data is complete.
Moderna aim to deliver approximately 500 million doses per year, and hope to extend this to possibly 1 billion doses per year, beginning in 2021. Strategic collaboration with Lonza and Catalent in the US, and ROVI in Spain, is set to facilitate the large-scale, global commercial distribution of mRNA-1273.
We reported just last week that the rival mRNA vaccine, BNT162b2, from Pfizer and BioNTech also had a high efficacy of >90% for the prevention of COVID-19.
Both vaccines are mRNA-based, and if either is approved it would represent a first-in-class as currently no such type of vaccine has been approved for an infectious disease.
mRNA-1273, encodes a prefusion stabilised form of the SARS-CoV-2 spike (S) protein encapsulated in a lipid nanoparticle and directs the body’s cells to express the spike protein in order to elicit an immune response.
One surprise from the emerging data on these new mRNA types of COVID-19 vaccines has been just how high the efficacy has been. To be considered for EUA, the FDA requires only a point estimate for a placebo-controlled efficacy trial of at least 50%. Whilst, both trials have not been completed, thus final efficacies might slightly vary, both far exceed expectations.
Meeting the global demand for a COVID-19 vaccines will be a huge challenge, and the more successful vaccines to meet approval, the better chance of succeeding this mission.
Whilst, mRNA vaccines are potentially more potent and straightforward to produce than traditional vaccines, meaning scaling up production may be far easier, they have the added complication of requiring specialist ultra-cold storage. How different ethnic, age or vulnerable groups differ in their response to individual vaccines is also likely to vary, as may the longevity of protection that is elicited by these different vaccines. Therefore, it may be that certain types of vaccine may be better suited to particular patient groups – all questions currently unanswered.
Whilst there are now currently 48 candidate vaccines in clinical evaluation for COVID-19 there is much hope resting on the 11 that are in Phase 3 trials.
One of the other front runners is the University of Oxford and AstraZeneca’s ChAdOx1 nCoV-19 vaccine, which is based on a well-studied and safe vaccine type – adenovirus vector.
The Oxford vaccine trial was the first to commence, and the results of their Phase 3 study is due imminently. With the UK Government ordering 100 million doses of the vaccine, enough to inoculate the whole of the UK, it should be easier to store and roll out than the other mRNA vaccines.
In fact with roll out obviously on Pfizer’s mind, it has been reported today that they have launched a pilot delivery program for their COVID-19 vaccine in four US states, as they seek to address distribution challenges facing the ultra-cold storage requirements.
However this story unfolds, it is likely that by the end of the year, one if not several of these trials will result in an approved COVID-19 vaccine and that a roll out of these will have been initiated – at least in a limited manner. We will be hoping that this indeed will be the very early beginnings of a route back to some resemblance of normality, and that it will give the world a fighting chance against this virus.
For more information please see the press release from Moderna