NIAID and Moderna have explained positive Phase I safety and efficacy data for their Covid-19 mRNA-1273 vaccine, highlighting the first comprehensive and clear outline of evidence that consecutive strokes at the dose selected for Phase III routinely produced a Swarm of antibodies against the virus that exceeded the levels observed in convalescent patients, generally in multiples that indicate a protective response.
Moderna executives clearly say that this early stage of research produced exactly the kind of efficacy they expected to see in humans, with a manageable safety profile.
“These Phase I data demonstrate that vaccination with mRNA-1273 elicits a robust immune response at all dose levels and clearly supports the choice of 100 μg in a prime and boost regimen as the optimal dose for the Phase 3 study. “Tal Zaks, CMO of Moderna, said in a prepared statement. “We hope to begin our Phase 3 study of mRNA-1273 this month to demonstrate the ability of our vaccine to significantly reduce the risk of COVID-19 disease.”
What we won’t have until Phase III data is available is clear evidence that the biomarker is an accurate indicator of efficacy in fighting the coronavirus outbreak. And it will still be necessary to answer a variety of important questions, which extend beyond the results of Phase III.
Investors were not waiting. Moderna’s shares soared 14% after the bell, adding billions more to a market capitalization that has increased to $ 29 billion.
The researchers tested 3 doses of the vaccine, which encodes cells to produce a stabilized form of the Spike protein seen in SARS-CoV-2 to elicit an immune response, preparing a person if they are faced with the real virus. They chose this particular code based on the sequence of the virus, an approach that could provide a shortcut to designing a vaccine, testing it in Phase I-III studies, and passing it on to billions of people. That process generally takes years, but Moderna and others have set out to do it in a matter of months, hoping for quick approval in the fall.
But like its mRNA rivals at BioNTech, Moderna is still in its infancy and has yet to gain approval for a vaccine or drug using this technology, putting each step of the process under a global microscope as analysts and experts look for flaws or concerns. .
For Moderna in particular, that means built-in skepticism for every move, despite having proof-of-concept data available for other conditions. In this case, with governments around the world eager to be the first to get the first vaccines approved, as hundreds of thousands die and the economic cost is in the billions, the stakes are huge.
Not to be overlooked: Moderna $ MRNA has offered more proof-of-concept human data that it can induce cells to produce a therapy or vaccine. If they win here, they will validate a full portfolio of projects and a market capitalization that has increased by billions this year. A loss would be devastating.
The latest data was published in the New England Journal of Medicine Tuesday.
According to Moderna:
After two vaccines, mRNA-1273 produced robust neutralizing antibody titers. On day 43, neutralizing activity against SARS-CoV-2 (PRNT80) was observed in all evaluated participants. At the selected Phase 3 dose of 100 μg, the geometric mean titer levels were 4.1 times higher than those observed in convalescent reference sera (n = 3).
After the second vaccination, neutralizing antibody titers of PsVNA were detected in all participants in all dose cohorts. The geometric mean titers of day 57 at the 100 μg dose were 2.1 times higher than those observed in convalescent sera (n = 38).
Strong correlations were observed between the binding and neutralization assays, and between the live virus and pseudovirus neutralization assays. A clear dose response was observed in geometric mean titers between the 25 µg and 100 µg dose levels, with minimal minimal increases at the 250 µg dose.
There were a variety of adverse events, which the researchers said were typically mild and transient. None were listed as serious adverse events. However, there were several “serious” high-dose adverse events that attracted rapid attention.
As a Phase I study, there are clear limitations in the data, especially considering the relatively small number of people involved, as well as the age group, which reached 55. How well the vaccine works in high-risk older people ? How durable is the effect?
In a companion article in the NEJM, Penny Heaton, CEO of the Bill & Melinda Gates Institute for Medical Research, picked up on the inevitable uncertainties that continue to circulate around the Phase I data.
Will a high dose of the Covid-19 vaccine be needed for effective protection of older adults, as seen with influenza vaccines? It will be necessary to confirm the clinical importance of neutralizing and SARS-CoV-2 binding antibody titers and their ability to predict efficacy.
These measures are currently being used to guide dose selection before being verified; they are the best tools available and are backed by findings in non-human primates. Confirmation of the correlation between antibody titers and protection against Covid-19 will only be possible in a large clinical efficacy study. In the meantime, it will also be necessary to document the validity of the assays to measure antibodies.
Volunteers in this study are being followed to assess durability and a phase III of 30,000 patients is slated to begin on July 27, fitting just below the July deadline that Moderna had set.
In a surprisingly short period of time, we will obtain the first comprehensive data sketch of this vaccine. But the scrutiny will last for years, under the best of circumstances.
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