Medical Innovation Exchange

Moderna’s early vaccine pipeline underpinned by Epstein–Barr, norovirus and shingles prospects

Moderna’s COVID-19 vaccine was a blockbuster. Highly anticipated shots protecting against respiratory syncytial virus and cytomegalovirus are on deck. 

Now the company’s third wave of potential products is building, with a trio of phase 1 candidates serving as the clinical backbone. 

Moderna illuminated the early progress in its vaccines day Wednesday, touching on roughly a third of the vaccines in its pipeline. The vaccine developer used the event to unveil data on several clinical-stage shots, including vaccines targeting the Epstein-Barr virus (EBV), norovirus and shingles.

More detailed data on a next-generation COVID vaccine were also disclosed, a day after Moderna said the prospect spurred a stronger immune response than its licensed shot, passing a phase 3 benchmark. 

An interim look at EBV vaccine mRNA-1189 found that it was generally well-tolerated and elicited a stronger immune response than the observed responses in those who were positive for the virus.

Though most infections from the virus are asymptomatic, being positive for the virus can increase the risk of some cancers, multiple sclerosis and infectious mononucleosis. 

The trial tested three doses and a placebo across four cohorts, recruiting a total of 272 seropositive and seronegative adults. Binding antibody titer levels were higher after a single shot of either three vaccine doses across three key proteins compared to baseline levels in seropositive patients who received a placebo. The vaccine also produced a strong B cell response, though it was higher in patients who were seropositive versus seronegative, Moderna said.

A pooled analysis of all three dose groups in patients who were seropositive found that vaccinated patients had less viral load in their saliva than patients given placebo. Moderna says it’s advancing mRNA-1189 toward pivotal development, while a second-generation vaccine focused on MS prevention continues to advance in a trial in healthy volunteers. 

“Clearly the questions of what we’re going to do on the MS endpoints and outcomes will take a little bit longer but obviously are much more valuable from a public health perspective,” Moderna president Stephen Hoge, M.D, said at the event.

Moderna’s shingles contender mRNA-1468 was also featured Wednesday, with the company showing that two doses elicited higher levels of T cells targeting CD4 and CD8 than GSK’s Shingrix, namely in the medium and higher dose groups. The trial randomized 500 patients across five cohorts, including 100 patients who received Shingrix. Systemic reactogenicity was comparable between Shingrix and the low and medium doses of mRNA-1468, with the higher dose posting elevated systemic side effects. Shingrix had the lowest levels of local reactions post-vaccination. 

Moderna’s head of infectious diseases, Jackie Miller, Ph.D., said the company is plotting future clinical development plans now and expects to need proof of vaccine efficacy for future approval. Whether that will need to be compared to Shingrix in a head-to-head trial remains to be seen. 

“We think that there’s a path forward since [Shingrix] isn’t universally available to potentially look at placebo-controlled,” she said. “However, we recognize that additional work against Shingrix is going to be important because that really is the benchmark and so we’re including that in our plans as well.” 

A norovirus vaccine was the third early candidate to get the interim readout treatment. The trial tested two investigational vaccines across 11 total arms, enrolling 664 people. The second dose of the vaccine was administered a month after the first.

Moderna’s presentation centered on one of the two, MRNA-1403, finding that the vaccine elicited a stronger immune response than placebo against two common norovirus genotypes. No safety concerns were identified through the data cutoff.  

The three batches of phase 1 data reinforce Moderna’s vaccine pipeline as it evolves beyond COVID-19. That doesn’t mean the event was devoid of data tied to the coronavirus, with Moderna expanding on phase 3 data from next-generation candidate mRNA-1283.222. The shot showed improved antibody response levels in trial participants 12 years and older, though the response was most muted in children 12 to 18.

“We believe this is really going to help enable combination vaccines because we found that with an adapted antigen we’re able to reduce interference,” Miller said. 

https://www.fiercebiotech.com/biotech/modernas-early-vaccine-pipeline-underpinned-three-sets-phase-1-data

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