Moderna’s COVID-19 Vaccine Gets Emergency Use Authorization From the FDA

Moderna’s COVID-19 Vaccine Gets Emergency Use Authorization From the FDA
Credit: Paul Biris/Getty Images

On Friday evening the FDA granted an emergency use authorization (EUA) to Moderna for its COVID-19 vaccine, the second vaccine EUA in a week, which will allow patients to be dosed with the company’s messenger RNA (mRNA)-based mRNA-1273.

The company said the first doses of mRNA-1273 will be injected into patients this week. Like Pfizer and BioNTech’s BNT162b2, which received an EUA on December 11, mRNA-1273 is a two-dose vaccine. But Moderna’s vaccine is indicated for the prevention of COVID-19 in individuals 18 years of age and older, rather than 16 and older as BNT162b2 is indicated.

“I am proud of what the Moderna team has achieved in collaboration with our partners,” Moderna CEO Stéphane Bancel said in a statement. “We were able to create and manufacture the Moderna COVID-19 vaccine in 11 months from sequence to authorization, while advancing clinical development with a Phase I, Phase II, and pivotal Phase III study of 30,000 participants.”

“It has been a 10-year scientific, entrepreneurial, and medical journey and I am thankful to all those who have helped us get here today,” Bancel added. “We remain focused on scaling up manufacturing to help us protect as many people as we can from this terrible disease.”

Washington plans to ship the initial 5.9 million doses of mRNA-1273 next week, U.S. Secretary of Health and Human Services Alex Azar II said Wednesday and again Thursday.

Tonight, Moderna repeated earlier statements that it plans to produce 20 million doses of mRNA-1273 by the end of this month, and between 100 million and 125 million doses during the first quarter, of which between 85 million to 100 million doses will be available in the United States. The company has said previously that it plans to produce between 500 million and 1 billion doses in 2021.

“We remain positive on the technology platform and strong outlook for mRNA-1273, and believe the co[mpany] is likely to hit their 500M dose base guidance in 2021 or likely exceed this,” Michael J. Yee, equity analyst with Jefferies, said Thursday in a research note.

Yee projected that 500 million doses “equates to around $10B in sales in our 2021 model, which is above consensus $8B+, though buyside expectation is $10B,” Yee added.

Jefferies recently downgraded Moderna from “Buy” to “Hold,” citing “elevated expectations in the wake of a 653% rally this year,” as well as data expected during the first quarter from rival COVID-19 vaccine developers—including Johnson & Johnson’s Janssen Pharmaceutical (JNJ-78436735); AstraZeneca (AZD1222  and AZD7442); and Novavax (NVX-CoV2373).

Unlike the Pfizer/BioNTech vaccine, which requires shipping and storage at -70º C, mRNA-1273 can be stored at 2º to 8º C, according to the protocol for Moderna’s approximately 30,400-patient Phase III COVE trial (NCT04470427). That is expected to widen the distribution of mRNA-1273, as is the vaccine’s availability in smaller batches than BNT162b2, which should extend the reach of Moderna’s vaccine into smaller hospitals like those in many rural and suburban areas.

“Highly effective”

The FDA set the stage for granting Moderna an EUA starting on Tuesday, when staff scientists issued a positive assessment of mRNA-1273 in a Briefing Document on the vaccine that was prepared for the agency’s Vaccines and Related Biologic Products Advisory Committee (VRBPAC).

The scientists reviewed data submitted by Moderna from the COVE trial. Moderna shared previously announced data showing mRNA-1273 to be 94.5% effective in an interim analysis based on 27,817 studied as of the data cutoff of November 7, and 94.1% effective in the trial’s final analysis.

“The two-dose vaccination regimen was highly effective in preventing PCR-confirmed COVID-19 occurring at least 14 days after receipt of the second dose,” the FDA researchers concluded.

The 21-member advisory committee recommended agency approval of mRNA-1273 by a 20-0 vote with one abstention: Michael G. Kurilla, M.D., Ph.D., who oversees the Clinical and Translational Science Awards (CTSA) Program as Director of the Division of Clinical Innovation at the NIH’s National Center for Advancing Translational Sciences, said VRBPAC should have recommended that patients access Moderna’s vaccine through an expanded access protocol rather than an EUA—and that mRNA-1273 be limited to high-risk patients.

“In the midst of a pandemic, and with limited vaccine supply available, a blanket statement for individuals 18 years and older is far too broad,” Kurilla said.

The margin of recommendation for mRNA-1273 was wider than the advisory committee’s 17-4-1 vote recommending approval of the Pfizer/BioNTech vaccine last week. Through its recommendation, the VRBPAC concluded that the benefits of Moderna’s vaccine outweighed its risks for use in individuals 18 years of age and older, based on the totality of scientific evidence available.

Moderna said last week it will evaluate mRNA-1273 in adolescents ages 12–17 through a separate clinical study, the Phase II/III TeenCove trial (NCT04649151), with data to be generated in the spring. Questions about the safety and effectiveness of the Pfizer/BioNTech vaccines in 16- and 17-year-olds led to the votes recommending against BNT162b2.

“With the availability of two vaccines now for the prevention of COVID-19, the FDA has taken another crucial step in the fight against this global pandemic that is causing vast numbers of hospitalizations and deaths in the United States each day,” FDA Commissioner Stephen M. Hahn, MD, stated.

He insisted the agency’s speedy review process not cut corners: “Through the FDA’s open and transparent scientific review process, two COVID-19 vaccines have been authorized in an expedited timeframe while adhering to the rigorous standards for safety, effectiveness, and manufacturing quality needed to support emergency use authorization that the American people have come to expect from the FDA.”

The FDA usually follows the recommendations of VRBPAC and other advisory committees.

mRNA-1273 is a novel lipid nanoparticle (LNP)-encapsulated mRNA vaccine encoding for a prefusion stabilized form of the Spike (S) protein. mRNA-1273 is among 20 “Front Runner” candidates among the more than 300 COVID-19 therapeutics under study in GEN’s “COVID-19 Drug & Vaccine Candidate Tracker.”

Going viral

During a discussion period before the vote, committee members discussed whether Moderna should be allowed to unblind patients randomized to placebo—something the company wants, saying it will increase the likelihood of retaining participants in the trial.

“ModernaTX expects that participants, including approximately 25% who are healthcare workers, may request unblinding to receive mRNA-1273 or another vaccine potentially available under EUA external to the trial,” according to the Briefing Document.

Committee members also discussed the possibility of mRNA-1273 preventing transmission of SARS-CoV-2 as well as protecting healthy adults from the virus; as well as the 11 participants who developed COVID-19 after being randomized to the vaccine, and what they might illustrate about the virus’ ability to mutate.

The 11 were among 196 cases of COVID-19 disclosed in the COVE trial’s final analysis—of which the other 185 were seen in patients randomized to placebo, and the other 11 in patients randomized to mRNA-1273.

There may be many more cases of vaccinated participants. Moderna is rechecking data on more than 450 cases of COVID-19 among COVE trial participants before it can pinpoint how many of the cases were in people who were vaccinated patients and how many in people who took placebo, Jacqueline Miller, MD, FAAP, Moderna’s senior vice president, infectious disease development, told VRBPAC members during the meeting. Miller joined Moderna on May 11 from GlaxoSmithKline.

“Additional severe cases and deaths are a question more of when than a question of if,” Miller said.

Moderna sponsors the COVE trial, which it is conducting in collaboration with the NIH’s National Institute of Allergy and Infectious Diseases and the Biomedical Advanced Research and Development Authority (BARDA).

Billions from Washington

BARDA is among federal agencies that have awarded up to $2.48 billion to Moderna toward R&D (up to $955 million), manufacturing, and delivery of 100 million doses of mRNA-1273 (up to $1.525 billion). Washington has also ordered an initial 100 million doses of BNT162 for $1.95 billion, with the option to purchase 500 million additional doses at an undisclosed price—an option that is now all but moot.

Scott Gottlieb, MD, President Trump’s first FDA commissioner and a Pfizer board member, told CNBC earlier this month that Washington passed up an offer by Pfizer in November to sell 100 million additional doses for delivery in the second quarter of 2021. The Department of Health and Human Services responded with a statement on Twitter that Washington’s COVID-19 vaccine development effort, dubbed “Operation Warp Speed,” never rejected “an offer from Pfizer for any number of millions of doses having a firm delivery date and quantity.” Not in dispute, however, is that most of the doses Pfizer has announced planned to produce have been purchased by other countries.

Gottlieb and Pfizer CEO Albert Bourla, DVM, PhD, have since said the company is in talks with the U.S. government to secure those 100 million doses. Both have expressed optimism that a deal will be worked out.

“We can provide a lot of that in the third quarter. The U.S. government wants it in the second quarter,” Bourla said on CNBC. “We are working very collaboratively to try to find a solution and be able to allocate those 100 million in the second quarter if possible or a lot of them.”

The first batch of mRNA-1273 was shipped on February 24, 42 days from sequence selection, to NIAID’s Dale and Betty Bumpers Vaccine Research Center (VRC), which partnered with Moderna in designing the vaccine. During a Synbiobeta “town hall” presentation in March, Moderna CEO Bancel said his company was able to develop its mRNA vaccine against COVID-19 quickly due to work it had done over the previous two years to develop a vaccine against MERS-CoV.

Moderna’s platform is based on injecting mRNA into cells to produce protein in human cells—an idea Bancel first viewed as crazy before realizing that making a human protein in a human cell is probably not going to be worse than making it in bacteria.

“We don’t guess the biology,” Bancel said, “we use the biology of nature.”