Early COVID-19 Vaccine Data Sets Up Moderna for Next Stages of Testing

Xconomy Boston — 

Moderna’s experimental COVID-19 vaccine is showing signs it can elicit antibodies at levels comparable to those found in the blood of dozens of patients who have recovered from the infectious disease, according to early results released Monday. The company is now preparing to quickly bring its vaccine candidate into the next stages of human testing.

The data for the Moderna vaccine, mRNA-1273, were reported from a small Phase 1 study enrolling 45 patients. Executives with Cambridge, MA-based Moderna (NASDAQ: MRNA) say the results inform the company about the safety of its vaccine and the best doses to evaluate going forward. A Phase 2 study enrolling hundreds of patients is expected to begin “shortly,” and a Phase 3 study enrolling thousands is planned to start in July, they said.

Moderna leads the pack of companies developing messenger RNA (mRNA) vaccines intended to coax cells into producing the protein that generates an immune response. The company’s vaccine candidate, mRNA-1273, delivers mRNA that codes for the “spike” protein of the novel coronavirus.

The Phase 1 study testing mRNA-1273 was conducted by the National Institute of Allergy and Infectious Diseases. The study enrolled 45 healthy volunteers between the ages of 18 and 55. Patients received an injection in the upper arm to start the study and a second dose after 29 days. Data are now available after two doses in the groups that received 25 microgram and 100 micrograms; and after one dose in the group that received 250 micrograms.

Moderna said Monday that antibodies were observed across all three doses by day 15. Two weeks after the second dose, the antibodies generated by the lowest dose reached levels seen in blood plasma from patients who have recovered from COVID-19, samples referred to as convalescent sera. At the middle dose, the antibody levels exceeded those in convalescent sera. Antibody data are not yet available for the high-dose group. Data about neutralizing antibodies, the type that would block infection and lead to immunity, were available for only eight patients—four each in the 25 microgram and 100 microgram groups.  The company said the neutralizing antibody levels were at or above levels seen in convalescent sera.

Side effects reported included fever, muscle pain, and headache, which Chief Medical Officer Tal Zaks said were typical for a vaccine. Most of those symptoms were gone the day after receiving the injection.

There was one report of a serious adverse event, which Zaks said was redness at the site of the injection in a patient who was in the group that received the high dose. Moderna won’t test that dose in the upcoming studies. The Phase 2 studies will evaluate two doses, 50 micrograms and 100 micrograms. Using a lower dose, assuming it is effective, means Moderna will be able to stretch its vaccine stock further to make more doses. “The lower the dose, the more people we expect to be able to protect,” Zaks said.

That’s also assuming mRNA-1273 is approved by the FDA. The Phase 2 study will help the company narrow down which dose to bring into Phase 3, Zaks said. The mid-stage study will also substantiate the safety information gathered from the Phase 1 study and better quantify the immune response observed. Moderna will launch the Phase 3 study even as it is still collecting and analyzing data from Phase 2, he said.

Developing and testing any vaccine typically takes years. CEO Stéphane Bancel acknowledged that Moderna is moving rapidly with its COVID-19 vaccine, but he noted that mRNA-1273 builds on previous research that the company had conducted in partnership with the National Institutes of Health in another coronavirus, Middle East respiratory syndrome (MERS). Also, the company has previous experience bringing mRNA vaccines into human testing. Before the pandemic, Moderna’s research focused on its clinical-stage cancer vaccines.

Bancel said that the COVID-19 research could inform Moderna’s approach to the clinical development of the rest of its pipeline. The planned Phase 3 study represents the largest clinical test of the Moderna technology—or any mRNA vaccine—to date. But first, the company needs to generate more data about mRNA-1273’s effects in humans. Asked whether a single dose will need to be followed by a booster shot later, Zaks responded that it’s too early to say.

“I don’t think we have any idea today what natural infection gives you in terms of long-term immunity let alone what a vaccine would do and how relevant waning immunity over the course of months and years is to a pandemic that may or may not circulate,” he said. “Great questions, but our entire history on the relevance of anything having to do with durability is no longer than four months since the start of following subjects, certainly in the US. Maybe five in China.”

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