Moderna Publishes Early COVID-19 Vaccine Data, Preps for Phase 3 Test

Xconomy Boston — 

Moderna’s COVID-19 vaccine candidate stimulated production of antibodies to the novel coronavirus in all of the patients tested in an early-stage study, and the company says the data support the selection of which dose to test in a pivotal clinical trial slated to begin at the end of July.

When the Cambridge, MA-based company initially reported unpublished data from the Phase 1 study in May, it could point only to preliminary results showing eight patients produced neutralizing antibodies—the type that protect against infection and lead to immunity. A more complete analysis of the study published in the New England Journal of Medicine now shows that these neutralizing antibodies were detected in all 45 study participants across all three of the doses tested.

The levels of neutralizing antibodies produced in patients given the middle and high doses were comparable, so Moderna (NASDAQ: MRNA) has selected the middle dose—100 micrograms—as the one that will be tested in a Phase 3 study expected to enroll 30,000 volunteers.

“We are now days away from recruiting healthy subjects,” Moderna CEO Stephane Bancel said on a conference call Wednesday.

Moderna is one of several companies developing a new type of vaccine based on messenger RNA, a snippet of genetic material that gets cells to produce a piece of the novel coronavirus. The Moderna vaccine candidate, mRNA-1273, codes for the spike protein found on the outer shell of the virus. While that protein isn’t enough to cause COVID-19 infection, it’s hoped to be sufficient to generate an immune response that confers some level of immunity.

The newness of COVID-19 means that scientists don’t yet know what measureable signs will show that a person is immune to the virus. But the published study says that neutralizing antibodies are used to evaluate immunity to other respiratory viruses, such as influenza and respiratory syncytial virus, and they are a generally accepted biological indicator.

The 45 patients in the Phase 1 study were split into three groups of 15, each group evaluating one of the three doses of mRNA-1273. The volunteers, ranging in age from 18 to 55, each received two shots given 28 days apart. Neutralizing antibodies were evaluated using two different tests.

After the first shot neutralizing antibodies were detected in less than half of the study participants, the published data show. But after the second injection, these antibodies were found in all of the patients, with higher responses observed in the middle and high dose groups. The study also showed an increase in levels of T cells, immune cells that could offer another avenue of protection against the virus.

The preliminary analysis only extends to 57 days following the first shot, which makes the durability of the immune response an open question. The Phase 1 study will continue to follow patients for one year. The evaluation will include periodic blood draws to measure antibody levels. The paper says that’s important because studies suggest that other coronavirus infections, such as SARS and Middle East respiratory syndrome, may not elicit a long-term antibody response.

No serious safety problems were reported in the study. Side effects typical of vaccines, such as redness and pain at the injection site, were mild to moderate, according to Tal Zaks, Moderna’s chief medical officer. Systemic side effects—fatigue, fever, chills, and muscle pain—were more common after the second injection. The most severe adverse events were observed at the high dose, which will not be given to those who enroll in Phase 2 and 3 studies.

In a research note, SVB Leerink analysts Geoffrey Porges and Daina Graybosch wrote that the increasing levels of neutralizing antibodies were encouraging. But the differences in the tests used to measure antibody levels makes it hard to compare the Moderna vaccine candidate against the mRNA COVID-19 vaccine in development by partners BioNTech (NASDAQ: BNTX) and Pfizer (NYSE: PFE). At this point it’s too early to conclude one vaccine is better at conferring immunity than the other, they wrote.

The analysts do see a signal that the immune response from Moderna’s experimental vaccine may be short-lived. Antibody levels declined from day 43 to day 57 of the study. That reduction could indicate that immunity from vaccination wanes, meaning that people who receive would need periodic booster shots to maintain protection. Speaking on the conference call, Zaks acknowledged the decline in antibody levels but said the data are fresh and that it’s too early to talk about the vaccine’s durability. He added that he’s reassured by the achievement of neutralizing antibody levels higher than those found in patients who sickened by COVID-19.

Moderna is preparing for the Phase 3 clinical trial of mRNA-1273 even as Phases 1 and 2 are ongoing. The early-stage study is continuing with seven additional seven groups—six of them evaluating the vaccine in older adults,who are at higher risk of severe illness from COVID-19. Moderna says it has completed enrollment of 75 additional patients, and that the company plans to publish preliminary data from these groups when ready.

Enrollment for the 600-patient mid-stage study is also complete. The trial is evaluating volunteers ages 18 to 55 in one group and those 55 and older in another arm. The study will test the low and middle doses to continue to evaluate the safety of the vaccine and its ability to produce an immune response.

The Phase 3 clinical trial evaluating the 100 microgram dose is expected to enroll 30,000 US patients. The main goal of the study is the prevention of the symptoms of COVID-19 disease. Secondary goals include prevention of severe COVID-19 disease—defined as the need for hospitalization—and prevention of infection by the novel coronavirus.

Zaks said that Moderna is working with the federal government’s Operation Warp Speed and the National Institutes of Health to ensure diverse study enrollment that is reflective of the population. Bancel said Moderna will provide its next update in early August when it reports its financial results from the second quarter.

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