Copyright The Boston Globe
“It’s obviously disappointing,” said Stephen Hoge, Moderna’s president, in an interview. Besides its Covid shot, the Cambridge-based company’s only other approved product, a vaccine for the respiratory syncytial virus, has significantly lagged entrants from Pfizer and GSK that were both earlier to market and appeared to have a more durable effect. It earned only $25 million last year. Sales of its Covid shots have slumped and it’s found itself in the crosshairs of a health secretary hostile to vaccines. CMV infections are lifelong and generally innocuous in healthy adults, but can be harmful when passed on from mother to child or in individuals with compromised immune systems. Infants can experience hearing or vision loss, as well as delays in developing movement skills. For people with compromised immune systems, such as organ transplant recipients, CMV infections can cause a host of problems and, in some cases, be fatal. In the study, more than 7,000 women of child-bearing age were randomized to receive either Moderna’s experimental vaccine or a placebo and then tracked to see whether they became infected with CMV. The vaccine was between 6% and 23% effective in blocking infection, depending on the criteria used, “well below the company’s target,” Moderna said in a statement. “There’s a huge burden of disease in congenital CMV,” Hoge said. “CMV is a silent virus, but one that causes a lot of damage, and the only way we could imagine running the study to try and see whether we could help in congenital CMV was prevention of infection.” That is a high bar, one that had not been met for CMV or other viruses in its family, herpes viruses. “Nobody succeeded ever, yet,” Hoge said. “And now you can add our name to that long list of companies and academics that haven’t been able to show benefit in CMV and infection.” The company had made big claims about the vaccine, and the failure of the study to meet its primary endpoint is likely to be interpreted as a miss for either Moderna’s mRNA technology, its clinical development prowess, or both. In 2020, Moderna CEO Stéphane Bancel gushed about the vaccine’s potential. It required the company to design a vaccine with six different individual components of the virus at once, something that’s incredibly difficult to pull off with more traditional technologies. “The pharma industry has strived for 20 years to develop a CMV vaccine. They have all failed,” Bancel told investors at a health care conference in November 2020. “I think this really shows the power of mRNA technology.” He boasted about Moderna’s ability to “do the right biology,” saying “we just mimic a natural infection without giving the virus.” In the wake of the success of its Covid vaccine, Moderna positioned CMV as the leading program in a larger portfolio of “complex viruses” where its mRNA technology could be used. But most of those programs have now been paused as Moderna tries to conserve costs. And lately some financial analysts had soured on the CMV vaccine’s potential. In August, analysts at Leerink, an investment bank, wrote that outside of Covid the CMV vaccine was the main focus but that odds of trial success were “dwindling.” “Even if some secondary endpoints suggest a benefit, a maternal mRNA vaccine is likely to face sharp scrutiny under current FDA leadership,” the Leerink analysts wrote. Moderna is still developing the CMV vaccine for patients undergoing a bone marrow transplant. In these patients, the removal of part of the immune system allows previous CMV infections to reassert themselves. In those studies, the vaccine would not need to prevent infection but to reduce hospitalization or meet other clinical endpoints — generally an easier hurdle for a vaccine to clear. Testing in that indication is only in Phase 2, and it is not clear what measures would be used in a Phase 3 trial. Hoge advised caution in drawing conclusions about Moderna’s other efforts based on the CMV data, noting that several of its lead programs already have proof-of-concept or clear efficacy data and none of its other vaccines are targeted to fully prevent infection. Moderna is also developing experimental medicines against melanoma and norovirus, as well as other vaccines. “We knew it was risky — it is unique in our pipeline,” Hoge said. “It’s not like we’re doing a lot of that everywhere. It’s the only one where we’re going after prevention of infection. And I do hope that anybody armchair quarterbacking where we are recognizes the other places that have been successful.” Under pressure from Wall Street to rein in a soaring research and development budget, Moderna had already spent the last two years cutting costs. Hoge said the failure would not impact the company’s guidance that it would break even in 2028, as Moderna expected the CMV vaccine, even if approved, would not earn significant revenue for several years. He also pointed out that the company would now not pay to build manufacturing or staff up a sales force for the vaccine. “It is disappointing for the long term, and that would be well beyond [2028],” he said. “But the Street and and, frankly, investors are calling for us to get the company on firm footing over the short term.”
