A key question for investors going forward will be whether Moderna’s other latent virus vaccines for Epstein-Barr and shingles can succeed after the failure of the CMV program.
Moderna will no longer invest in its congenital cytomegalovirus program after the investigational vaccine mRNA-1647 failed to elicit strong protection in a late stage trial.
The company did not provide a specific readout in a news release on Wednesday, revealing only that mRNA-1647 achieved between 6% and 23% efficacy in preventing cytomegalovirus (CMV) infection in female study participants aged 16 through 40 years. CEO Stéphane Bancel in a statement called this outcome “disappointing,” nevertheless promising that Moderna will share “forthcoming” data with the broader scientific community “in hopes that our learnings can contribute to the continued pursuit of a CMV vaccine.”
Trouble for the CMV program has been brewing for several months. Moderna was supposed to provide an interim readout for the program after reaching 81 cases of CMV, so long as efficacy met the bar for statistical significance, William Blair wrote on Thursday morning. But the study’s safety monitoring board declared that this marker had not been met in January. The readout was delayed again last quarter as Moderna changed up the analysis protocol for some of the secondary endpoints.
“Ultimately, we view failure of the CMVictory trial as an incremental setback for Moderna given low investor expectations after it missed the prior interim analysis,” William Blair said.
Moderna’s shares fell just under 4% to $25.84 in pre-market trading on Thursday morning.
CMV is a common infection that affects people of all ages—so much so that almost 1 in 3 children will have been infected with the virus when they reach 5 years. Symptoms include fever, sore throat, fatigue and swollen glands.
Though CMV is often mild, a particularly at-risk population is pregnant women, who run the risk of passing the virus on to their kids.
CDC data indicate that around one in 200 newborns have congenital CMV; of these, approximately 20% will suffer from birth defects and long-term health problems. Of all infectious diseases, CMV is responsible for the most cases of birth defects in the U.S., the agency said.
Moderna’s answer to CMV is mRNA-1647, an mRNA vaccine that encodes for two key CMV proteins: glycoprotein B and pentametric complex, both of which help the virus attach to and infiltrate target host cells. The asset is one of Moderna’s longest-running programs, with Phase I development beginning as early as 2017.
Moderna’s mRNA platform is still performing well enough in preventing infections from acute-phase viruses, William Blair noted. However, the CMVictory miss suggests the technology might not work as well for latent viruses, which lie dormant in the body. This miss and whether it has read through to other Moderna programs will be a “key question for investors moving forward,” the analysts wrote. Moderna is developing multiple vaccines for latent viruses Epstein-Barr and shingles.
Despite ending the congenital CMV program, Moderna plans to continue testing mRNA-1647 in bone marrow transplant patients, for which the company has an ongoing mid-stage trial, according to the Wednesday release. The Phase III fail is also unlikely to affect Moderna’s full-year guidance or its goal of breaking even in 2028, the company said.
Moderna is in the midst of an aggressive cost-cutting campaign. In September 2024, the company announced plans to slash its R&D budget by $4 billion through 2028, with the goal of reaching a breakeven point, on an operating cash basis, that same year. In May this year, Moderna tacked $1.5 billion more onto this savings target. In line with these cuts, Moderna laid off 10% of its workforce in July, bringing its global headcount to just under 5,000.
