The first interim analysis is based on 95 participants with confirmed COVID-19 in the 30,000-strong Phase 3 study.
Moderna will submit a request for Emergency Use Authorisation (EUA) in the ‘coming weeks’.
Last week Pfizer and BioNTech reported a similarly high efficacy (of ‘more than 90%') for their mRNA vaccine candidate.
Moderna, however, champions new stability data for its vaccine revealed this morning: the vaccine only requires standard freezer temperatures of -20°C for shipping and storage (compared to -70°C (-94 F) for Pfizer's vaccine candidate).
Primary efficacy endpoint met
The primary endpoint of Moderna's COVE study is based on the analysis of COVID-19 cases confirmed and adjudicated starting two weeks after the second dose of the 2-dose vaccine is administered.
Out of the 95 cases in the interim analysis, 90 were observed in the placebo group while five were in the vaccine group.
A secondary endpoint looked at severe cases of COVID-19. In this interim analysis, 11 cases occurred in the placebo group and none occured in the vaccinated group.
The 95 COVID-19 cases included 15 adults aged over 65 years old; and 20 participants identifying as being from diverse communities (including 12 Hispanic or LatinX, four Black or African Americans, three Asian Americans and one multiracial).
“This is a pivotal moment in the development of our COVID-19 vaccine candidate," said Stéphane Bancel, Chief Executive Officer of Moderna. "Since early January, we have chased this virus with the intent to protect as many people around the world as possible.
"This positive interim analysis from our Phase 3 study has given us the first clinical validation that our vaccine can prevent COVID-19 disease, including severe disease. This milestone is only possible because of the hard work and sacrifices of so many.
"I want to thank the thousands of participants in our Phase 1, Phase 2 and Phase 3 studies, and the staff at our clinical trial sites who have been on the front lines of the fight against the virus. They are an inspiration to us all.
"We look forward to the next milestones of submitting for an EUA in the US, and regulatory filings in countries around the world, while we continue to collect data on the safety and efficacy of the vaccine in the COVE study. We remain committed to and focused on doing our part to help end the COVID-19 pandemic.”
The interim analysis was initially set to take place when 53 cases had occured. A significant increase in the rate of COVID-19 cases, however, meant the first interim anaysis was carried out with 95 cases (This is similar to Pfizer's interim analysis, which evaluated 94 cases).
Moderna's primary analysis will be carried out at 151 cases, according to the company's study protocol.
No significant safety concerns
A concurrent review of Phase 3 safety data by the DSMB did not report any signficant safety concerns.
"A review of solicited adverse events indicated that the vaccine was generally safe and well tolerated," says a statement from Moderna.
"The majority of adverse events were mild or moderate in severity. Grade 3 (severe) events greater than or equal to 2% in frequency after the first dose included injection site pain (2.7%), and after the second dose included fatigue (9.7%), myalgia (8.9%), arthralgia (5.2%), headache (4.5%), pain (4.1%) and erythema/redness at the injection site (2.0%).
"These solicited adverse events were generally short-lived."
Shipping and storage requirements
Releasing new stability data this morning, Moderna says its vaccine candidate is now expected to remain stable at standard refrigerator temperatures of 2° to 8°C (36° to 46°F) for 30 days (initial estimates had put this at 7 days).
Shipping and long-term storage conditions would keep the vaccine at standard freezer temperatures of -20°C (-4°F) for 6 months. Moderna highlights that most pharmaceutical distribution companies already have the capabilities to store and ship vaccines worldwide at this temperature.
Juan Andres, Chief Technical Operations and Quality Officer at Moderna, said: “We believe that our investments in mRNA delivery technology and manufacturing process development will allow us to store and ship our COVID-19 vaccine candidate at temperatures commonly found in readily available pharmaceutical freezers and refrigerators.
“We are pleased to submit these extended stability conditions for mRNA-1273 to regulators for approval. The ability to store our vaccine for up to 6 months at -20° C including up to 30 days at normal refrigerator conditions after thawing is an important development and would enable simpler distribution and more flexibility to facilitate wider-scale vaccination in the US and other parts of the world.”
The vaccine will not require onsite dilution or any other special handling.
Moderna intends to submit for an Emergency Use Authorization (EUA) with the U.S. Food and Drug Administration (FDA) in the 'coming weeks' and anticipates having the EUA informed by the final safety and efficacy data (with a median duration of at least 2 months for safety data as required by the FDA).
Moderna says it also plans to submit applications for authorizations to global regulatory agencies (Switzerland's Swissmedic began a rolling review on Friday; the UK's MHRA and Health Canada both began a rolling review in October; and Europe's EMA has confirmed eligibility for the submission of a marketing authorization application).
By the end of 2020, Moderna expects to have approximately 20 million doses of mRNA-1273 ready to ship in the US. The company plans to manufacture 500 million to 1 billion doses globally in 2021.
The vaccine and Phase 3 COVE trial
Moderna's COVID-19 vaccine candidate (mRNA-1273) is an mRNA vaccine against COVID-19 encoding for a prefusion stabilized form of the spike (S) protein, which was co-developed by Moderna and investigators from NIAID’s Vaccine Research Center.
The vaccine is given in two doses, 28 days apart.
Moderna completed enrolment of 30,000 people for its US Phase 3 trial in October. This figure includes:
- more than 7,000 people over 65 years old;
- 5,000 people under the age of 65 but with high-risk chronic diseases that put them at increased risk of severe COVID-19 (for example, diabetes, severe obesity and cardiac disease)
- 11,000 participants from communities of color (ie, 37% of the study population and similar to the diversity of the US): including 6,000 Hispanic/LatinX; and 3,000 Black/African American.
Developing mRNA-1273: the timeline to date
Pre-2020: Moderna had eight mRNA vaccines in development against viruses such as Zika, RSV and influenza
January 23, 2020: Moderna receives funding award from CEPI to accelerate development of an mRNA vaccine candidate against COVID-19
March 16: First participant dosed in Phase 1 study for mRNA-1273 in the US
April 16: Moderna receives award of up to $483m from US government agency BARDA for its mRNA vaccine development
May 11: Moderna receives FDA Fast Track Designation for its vaccine candidate
July 27: Phase 3 trial begins
October 22: Phase 3 study completes enrolment of 30,000 people
November 13: Swissmedic (Switzerland) becomes the latest to begin its rolling review of the vaccine, following on from similar processes started in October by the UK’s MHRA and Health Canada.
November 16: Moderna releases interim analysis for its Phase 3 trial, reporting 94.5% efficacy and meeting primary efficacy endpoint.
‘in the coming weeks’: Request for EUA to be submitted to the US’ FDA
2022: End of Phase 3 trial (participants will be followed for 24 months after the second dose is administered).