Two months ago, Moderna trumpeted “positive” early data for its COVID-19 vaccine but didn’t offer the results in a scientific presentation or in a peer-reviewed study. Now, it’s showing us the receipts.
The phase 1 study, being run by the National Institute of Allergy and Infectious Diseases, is testing three dose levels of the vaccine, mRNA-1273, given in two injections a month apart in 45 adults. At day 43, about two weeks after they got the second dose, all evaluated patients had “robust” levels of neutralizing antibodies against SARS-CoV-2, the virus that causes COVID-19, according to a study published Tuesday in The New England Journal of Medicine. Three patients did not get a second dose—one because of a skin reaction and two because they were isolated while waiting for COVID-19 test results.
Despite the "robust" responses, the investigators noted that "correlates of protection from SARS-CoV-2 infection have not been determined." But if the new coronavirus works the way other respiratory viruses do, it's reasonable to expect high levels of neutralizing antibodies to correspond with protection.
The investigators measured patients’ antibody levels using two different tests and compared them to results from 38 patients who had recovered from the disease. The bulk of those recovered patients had mild COVID-19, while 22% had moderate symptoms and 15% had severe disease and needed to be hospitalized or put on a ventilator.
One measure found that patients who took the middle dose, 100 micrograms, had four times the antibody level that the recovered patients had. The second measure found those patients had twice the antibody level of the recovered patients. Whichever way you slice it, it’s good news, wrote Jefferies analyst Michael Yee in an investor note.
“Rather than getting too analytical about the ratio, the level of neutralizing antibodies are high and well above convalescent sera, realizing that convalescent sera comparator antibody levels have a wide range for patients who resolve (e.g. we have seen levels between 50-200+). This is because severe patients could have more antibodies than milder patients,” Yee wrote.
There were no serious side effects through day 57, about two months after the second dose. Half of the patients on the lowest dose, 25 mcg, experienced systemic side effects including fatigue, headache, chills and muscle pain. All of the patients on the middle dose, 100 mcg, and the highest dose, 250 mcg, experienced these kinds of effects, but they were “transient and moderate or mild in severity.”
“Bottom line, the data affirms our positive thesis that early vaccine data continues to look very promising, and has a very reasonable likelihood of working and protecting against infection,” Yee wrote, adding that the vaccine should meet the bar for an emergency use authorization and become available for governments by the end of 2020 or in early 2021.
“These Phase 1 data demonstrate that vaccination with mRNA-1273 elicits a robust immune response across all dose levels and clearly support the choice of 100 µg in a prime and boost regimen as the optimal dose for the Phase 3 study,” Tal Zaks, M.D., Ph.D., chief medical officer of Moderna, said in a statement. “We look forward to beginning our Phase 3 study of mRNA-1273 this month to demonstrate our vaccine’s ability to significantly reduce the risk of COVID-19 disease.”
The published data come from 45 adults aged 18 to 55, but study is also looking at older adults aged 56 to 70 and aged 71 and older. A phase 2 study is evaluating two doses of the vaccine, 50 mcg and 100 mcg, in 300 adults split into two groups: those under 55 and those over 55.
As for the phase 3 trial, Moderna aims to recruit about 30,000 patients in the U.S. to test the middle dose of the vaccine. Dubbed the COVE study, it will look at whether the vaccine can ward off symptomatic COVID-19 infection as well as whether it can prevent patients from needing hospitalization. The company aims to kick off the study July 27, according to the statement.
Beyond making enough doses for the phase 3 program, Moderna expects to manufacture about 500 million doses a year and possibly scale that up to 1 billion doses per year starting in 2021, thanks to a partnership with Lonza. It’s also enlisted Catalent to help out on the finishing stages of the vaccine and Spain’s Laboratorios Farmacéuticos Rovi to help bring the vaccine to markets outside the U.S.
Shares in the biotech jumped 16% in premarket trading Wednesday morning on the data drop.