More Good News for COVID-19Vaccines as Moderna Reports

Preliminary Results

Interview with Wayne Ko PhDPresident and CEO

Human Vaccines Project

An interim analysis released today indicates that Modernarsquos mRNA-based COVID-19vaccine candidate is nearly 95 eective making it the second candidate to show such ahigh-level of ecacy Last week Pzer and BioNTech reported their mRNA vaccinecandidate was more than 90 eective based on an interim analysis These results havespurred optimism among public health ocials who are struggling to control a surgingpandemic and have exceeded the expectations of many vaccine experts HVP Editor Kristen Jill Abboud discussed these latest results with Wayne Ko foundingPresident and CEO of the Human Vaccines Project (HVP) An edited version of theconversation appears below This special issue also includes reactions from severalexperts in the eld and a summary of Modernarsquos ongoing Phase III ecacy trial includingtrial demographics and their plans for submitting their vaccine for regulatoryauthorization

Moderna reported that of the 95 COVID-19 cases in the trial so far 90 wereamong placebo recipients and only ve were among vaccine recipients whichcorresponds to an ecacy of 945 What is your initial response to this news

The ecacy they are seeing is once again extraordinary It is as promising of aresult as anyone could have hoped for These results are a rearmation of mRNAas a vaccine platform It also arms the targeting of the Spike (S) protein of thevirus which is what most of the vaccine candidates are based on That said weawait data on the durability of the vaccine-induced responses Based on what weknow however this is very encouraging Now we eagerly await data being fullyreported in a peer-reviewed publication because it is dicult to fully analyze theresults until that happens

Among the 95 COVID cases analyzed so far in both vaccine and placebo groups15 of the volunteers were over 65 years old and 20 volunteers were from whatthe press release refers to as ldquodiverse communitiesrdquo The company also reportsthat the safety and ecacy prole is consistent across subgroups Does this giveyou condence that when the trial is complete we will have a reasonableunderstanding of how the vaccine works in these populations

This trial involves more than 30000 participants and they have enrolled a lot ofpeople over age 65 and in diverse communities so I think we will get the data onthe ecacy in these populations This information is going to be really importantbecause as wersquove seen individuals over the age of 65 and those in diverseracialethnic populations are more likely to die as a result of COVID-19 If there is aconsistent level of safety and ecacy among these sub-populations that would bereally great news

This mRNA vaccine seems to protect against cases of severe disease but thereisnrsquot yet any data on prevention of infection Is there any vaccine platform inparticular that stands out as being the most likely to protect against infection

The initial data on severe disease is fabulousmdashall 11 cases of severe disease thathave been observed so far have occurred among placebo recipients This ispreliminary and is based on a small number of severe cases but this is still a reallyimportant observation Its hard to know which vaccines will work better atpreventing infection because the vaccine platforms are quite dierentmdashmRNArecombinant protein viral vectors and live and killed vaccines Also they are allusing somewhat dierent assays to analyze the immune responses and have yet tobe compared head-to-head with standardized assays

Do these results as well as those from Pzer and BioNTech suggest that mRNAis going to deliver on all of its promise as a vaccine platform

This is really the only data that validates this platform but it is fabulous news forthis approach with the caveat that we donrsquot know about the durability of theprotection nor do we have long-term safety data What we have seen on the safetydata so far looks really promising Most of the other mRNA vaccine candidates haveonly progressed through early phase clinical trials Moderna has several othervaccine candidates in the clinic but they havenrsquot gone as far as the COVID vaccinecandidate and they certainly havenrsquot gone as fast

How important is the dierence in the temperature that is required for storagebetween the Moderna candidate and the PzerBioNTech candidate

The updated information Moderna released on stability is really important becauseit enables the use of the existing cold-chain apparatus to deliver the vaccine allover the world Instead of requiring ultra-cold temperatures this vaccine can bestored in a normal freezer for up to six months and remains stable for up to amonth in a refrigerator This is a really important observation

It is exciting to think that very soon there will be two vaccines being considered foreither Emergency Use Authorization or licensure by the FDA [US Food and DrugAdministration] What will really matter is getting this vaccine into the arms ofpeople particularly those in the groups at highest risk as soon as possibleHopefully the good news continues

Interview by Kristen Jill Abboud

Reactions from the Field

Richard Hatchett MD CEO Coalition for EpidemicPreparedness InnovationsldquoThe Moderna results are as good as we could have hopedfor and really terrically encouraging The fact that thevaccine shows stability when stored in a normalrefrigerator for up to 30 days is also terric news and willallow the vaccine to be distributed broadly We areaccumulating the tools we will need to end the pandemicIt is a great day for Moderna for mRNA vaccines and forthe worldrdquo

Michelle Williams ScD SM Dean of the FacultyHarvard TH Chan School of Public HealthldquoThe news about the Moderna vaccine coming on theheels of Pzerrsquos announcement a week ago is hearteningand a testament to the tireless work of our nationrsquosscientists and researchers These are still early days ofcourse and we need to be patient as we await morecomplete data to better assess the ecacy of thesevaccines Controlling this pandemic is ultimately aboutvaccinations not vaccines and we need to start planningnow in order to hit the ground running once thesevaccines are deemed safe for public distributionrdquo

Myron S Cohen MD Yeargan-Bate Professor ofMedicine Microbiology and Epidemiology DirectorInstitute for Global Health and Infectious DiseasesUniversity of North Carolina at Chapel HillldquoThe remarkable positive results from Moderna and Pzerprovide us our rst powerful biological tools to thepandemic Now the hard work of vaccination whileretaining essential safe behaviors beginsrdquo

Glenda Gray MBBCH FCPaed(SA) DSc (honoriscausa) President and CEO South African MedicalResearch Council Research Professor of PediatricsUniversity of the Witwatersrand Director Perinatal HIVResearch Unit SowetoldquoThe nding that this vaccine was highly eective againstsevere disease will make a huge contribution in reducingmortality from COVID-19 Also knowing that these resultsconcur with Pzerrsquos mRNA COVID-19 vaccine is reassuringfor the eld We remain hopeful that the other vaccineplatforms will be as eective giving the world amplevaccines to increase accessrdquo

Jaap Goudsmit MD PhD Chief Scientic Ocer of theHuman Immunomics Initiative Adjunct Professor ofEpidemiology and Immunology Harvard TH ChanSchool of Public HealthldquoTo me the surprise is not that the ecacy looks great butthat the stability is better which makes vaccinationcampaigns signicantly easierrdquo

John Moore PhD Professor of Microbiology andImmunology Weill Cornell Medical CollegeldquoThe Moderna ecacy rate is consistent with what Pzerreported last week which is a very good indicator thatmost and perhaps all of the Operation Warp Speedvaccines will turn out to be valuable for curtailing thepandemic during the rst half of 2021 We also now havean insight from the Moderna data that these vaccines canalso prevent severe disease another strong positive It wasalso good to see additional data on vaccine stability undertemperature conditions that will surely help with rolloutpost approvalrdquo

Marie-Paule Kieny PhD Director of Research InsermBoard MemberThe Human Vaccines Project ldquoTogether these two announcements show that aneective vaccine against COVID-19 is feasible thatextremely high ecacy is reachable and that we will mostlikely have vaccines available for deployment in thecoming weeks or months Of course information is stilllacking on long-term safety duration of protection ecacyin the elderly and reduction of viral transmission butwhat we know is already great newsrdquo

Barton Haynes MD Frederic M Hanes DistinguishedProfessor of Medicine Immunology and Global HealthDirector Duke Human Vaccine Institute and the Centerfor HIV-AIDS Vaccine ImmunologyldquoThese results are very encouraging not only because ofthe high degree of protection but also because people ofcolor and older individuals with predisposing conditionswere included in the trial It will be of great interest to seethe durability of the antibody responses as they arefollowed over timerdquo

James E Crowe Jr MD Director Vanderbilt VaccineCenterldquoThe preliminary results announced by Moderna areexciting for several reasons First we appear to haveanother COVID vaccine with better-than-hoped-for ecacywhich will help us combat the current epidemic Secondthe success of this trial points the way to the use of thisand other mRNA platforms in other programs forinfectious diseases possibly enabling a whole new era ofvaccine successesrdquo

Galit Alter PhD Professor of Medicine Harvard MedicalSchool Director Ragon Institute Imaging Core andHarvard Institute for AIDS Research Immunology CoreldquoThe results from Pzer and now Moderna mark thedawning of a new day for vaccine development as bothrapid mRNA platforms have shown impressive ecacyagainst the development of COVID-19 disease invaccinated individuals The exibility with which mRNAvaccines can be designed gives us the speed we need toprevent future epidemicsrdquo

Adrian Hill Professor of Human Genetics Director of theJenner Institute Co-Director Oxford Martin Programmeon Vaccines University of Oxford Wellcome Trust SeniorInvestigatorldquoThis is welcome news indicating ecacy from anothercandidate vaccine showing that it is clearly possible tocreate eective vaccines within a year in response to aglobal pandemic Hopefully this will lead to a major re-think on development timelines for vaccines against otherinfectious diseases that kill large numbers of peoplerdquo

Peter Piot KCMG MD PhD DTM FRCP FFPHFMedSci Director and Handa Professor of Global PublicHealth London School of Hygiene and Tropical Medicine ldquoAnother remarkable vaccine result There is nally hopefor getting out of this crisis It is now key to do everythingwe can to limit the spread of the virus and save lives bysafe behavior in the coming monthsrdquo

Trial Summary

Protocol title A Phase III Randomized Stratied Observer-Blind Placebo-Controlled Study to Evaluate the Ecacy Safety and Immunogenicity ofmRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 18 Years and Older

Study Sponsor ModernaTX Inc Collaborators US National Institute of Allergy and Infectious Diseases (NIAID)part of the US National Institutes of Health and the Biomedical AdvancedResearch and Development Authority (BARDA) Vaccine candidate tested mRNA-1273 Protocol summary On October 22 the Phase III COVE study of mRNA-1273completed enrollment of 30000 participants in the US The randomized 11placebo-controlled Phase III trial is studying mRNA-1273 at the 100 microg doseThe primary endpoint is the prevention of symptomatic COVID-19 disease Keysecondary endpoints include prevention of severe COVID-19 disease andprevention of infection by SARS-CoV-2 The ClinicalTrialsgov identieris NCT04470427 Number of volunteers 30000 participants in the US were enrolled in theCOVE Phase III Study as of Thursday October 22 2020 and 25654 participantshave received their second vaccination Age groups Adults ages 18 and up (stratied by ages 18-24 25-44 45-64 65 orabove) More than 7000 volunteers are over 65 years old Demographics 63 White 20 HispanicLatinX 10 BlackAfrican American4 Asian 3 All Others More than 5000 volunteers are under the age of 65but have high-risk chronic diseases that put them at increased risk of severeCOVID-19 disease such as diabetes severe obesity and cardiac diseaseThese high-risk groups represent 42 of the total participants in the Phase IIICOVE study Results summary The primary endpoint of the Phase III COVE study is basedon the analysis of COVID-19 cases conrmed and judged starting two weeksfollowing the second dose of vaccine This rst interim analysis was based on95 cases of which 90 cases of COVID-19 were observed in the placebo groupversus 5 cases observed in the mRNA-1273 group resulting in a pointestimate of vaccine ecacy of 945 (p lt00001) A secondary endpointanalyzed severe cases of COVID-19 and included 11 severe cases (as denedin the study protocol) in this rst interim analysis All 11 cases occurred in theplacebo group with none occurring in the mRNA-1273 vaccinated group The95 COVID-19 cases included 15 older adults (ages 65+) and 20 participantsidentifying as being from diverse communities (including 12 Hispanic orLatinX 4 Black or African Americans 3 Asian Americans and 1 multiracial)The side eects of the two-dose vaccine were mostly mild or moderateincluding pain at the injection site fatigue headache and muscle pain Allinformation was provided in Modernarsquos press release Next steps As more cases accrue leading up to the nal analysis Modernaexpects the point estimate for vaccine ecacy may change Moderna plans tosubmit data from the full Phase III COVE study to a peer-reviewed publicationBased on these interim safety and ecacy data Moderna intends to submitfor an Emergency Use Authorization (EUA) with the US Food and DrugAdministration (FDA) in the coming weeks and anticipates having the EUAinformed by the nal safety and ecacy data (with a median duration of atleast 2 months) Moderna also plans to submit applications for authorizationsto global regulatory agencies Previous data published in The New England Journal of Medicine Safety andImmunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults Evaluationof the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates AnmRNA Vaccine against SARS-CoV-2 mdash Preliminary Report

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