Moderna said today it will seek FDA emergency use authorization (EUA) and a European conditional approval of its COVID-19 vaccine candidate, after confirming the efficacy of mRNA-1273 with additional positive Phase III data released this morning.

The company cited a primary efficacy analysis by the study’s independent, NIH-appointed Data Safety Monitoring Board (DSMB) of data from the 30,000+ patient Phase III COVE trial (NCT04470427), an analysis based on 196 cases of COVID-19. Of those cases, 185 were seen in patients randomized to placebo, and the other 11 in patients randomized to mRNA-1273.

The 196 COVID-19 cases included 33 adults ages 65+, and 42 participants identifying as being from diverse communities—including 29 Hispanic or LatinX, six Black or African Americans, four Asian Americans, and three multiracial participants. Moderna said the efficacy of mRNA-1273 was consistent across age, race and ethnicity, and gender demographics.

“A very high bar”

“This sets a very high bar for other programs coming because the efficacy bar is high, efficacy is strong regardless of age,” and no severe COVID-19 attributable to the vaccine was reported Michael J. Yee, equity analyst with Jefferies, concluded this morning in a research note.

Yee contrasted Moderna’s results with those announced last week by AstraZeneca for AZD1222, the COVID-19 vaccine candidate it is co-developing with the University of Oxford and a university spinout. While AstraZeneca trumpeted a 90% vaccine efficacy when AZD1222 was given as a half dose, followed by a full dose at least one month apart, the half dose cohort included no older adult participants—something AstraZeneca is expected to address when it carries out a future global trial promised last week by the company to compare the effectiveness of the half-plus-whole dose regimen to the regimen of two whole doses.

Moderna and AstraZeneca are among developers of three leading COVID-19 vaccine candidates to report positive Phase III data in recent days. Pfizer and BioNTech on November 20 applied for an EUA for their mRNA-based vaccine BNT162b2.

The number of cases was more than double the total of 95 cases assessed in the first interim analysis based on the pre-specified success criterion on efficacy. The study’s primary endpoint is significantly fewer COVID-19 cases confirmed and adjudicated starting two weeks following the second dose of vaccine compared with patients randomized to placebo.

Moderna also said a secondary endpoint analyzing 30 severe cases of COVID-19 showed all of them to have occurred in the placebo group and none in the mRNA-1273 vaccinated group. The company acknowledged one COVID-19-related death in the study to date, but said the death occurred in the placebo group.

“This positive primary analysis confirms the ability of our vaccine to prevent COVID-19 disease with 94.1% efficacy and importantly, the ability to prevent severe COVID-19 disease,” Moderna CEO Stéphane Bancel said in a statement. “We will file today for an Emergency Use Authorization from the FDA and continue forging ahead with the rolling reviews that have already been initiated with several regulatory agencies around the globe.”

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 one of 20 “Front Runner” candidates among the more than 300 COVID-19 therapeutics included in GEN’s updated “COVID-19 Drug & Vaccine Candidate Tracker.”

December 17 advisory panel meeting

Moderna said the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) is expected to review the safety and efficacy data package for mRNA-1273 at a meeting scheduled for December 17. The FDA typically follows the recommendations of its advisory panels. Upon granting of an EUA, Moderna said, it anticipates that the shipping of mRNA-1273 to designated distribution points throughout the U.S. will occur.

Moderna said it is working with the U.S. Centers for Disease Control and Prevention, Operation Warp Speed—the Trump administration’s effort to accelerate development of COVID-19 vaccines and drugs—as well as McKesson, a COVID-19 vaccine distributor contracted by the U.S. government, and other global stakeholders assisting the company in distributing mRNA-1273, in the event that it receives an EUA and similar global authorizations and approvals.

In addition to the EUA, Moderna will also apply for a Conditional Marketing Authorization (CMA) with the European Medicines Agency. The company has already begun a rolling review process with the EMA, as well as Health Canada, SwissMedic, the United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA), Ministry of Health in Israel, and Health Sciences Authority in Singapore.

Moderna added that it also intends to seek Prequalification (PQ) and/or Emergency Use Listing (EUL) with the World Health Organization (WHO).

Moderna today restated earlier assurances that by the end of 2020, it expects to have approximately 20 million doses of mRNA-1273 available in the U.S. The Company remains on track to manufacture 500 million to 1 billion doses globally in 2021.

On November 10, the American Medical Association (AMA) issued a Current Procedural Terminology (CPT) code of 91301 to report vaccination with mRNA-1273.

“New and powerful tool”

“We believe that our vaccine will provide a new and powerful tool that may change the course of this pandemic and help prevent severe disease, hospitalizations and death,” Bancel added.

Yee of Jefferies added that the positive results shown by the mRNA platform being used for mRNA-1273 augur well as future mRNA-based vaccines of Moderna. These include mRNA-1647 (Cytomegalovirus (CMV) vaccine), mRNA-1893 (Zika), mRNA-1653 (hMPV/PIV3 vaccine), mRNA-1345 (Pediatric respiratory syncytial virus (RSV) vaccine and a possible future respiratory combination vaccine), mRNA-1851 (Influenza H7N9 vaccine), and mRNA-1189 (Epstein-Barr virus (EBV) vaccine). All but the EBV vaccine are in clinical phases of development.

“The additional vaccines in MRNA’s pipeline are even more likely to be best-in-class including CMV, flu vaccine, etc.,” Yee observed. “This is important for the pipeline and platform value at MRNA to support an ‘engine’ of mRNA programs coming in the future.”

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