Moderna announced today that its Phase 3 pivotal trial evaluating mRNA-1647, an investigational cytomegalovirus (CMV) vaccine, failed to meet its primary efficacy endpoint of preventing CMV infection in seronegative female participants of childbearing age. The disappointing results have prompted the company to discontinue its congenital CMV clinical development program entirely.
Trial Design and Results
The Phase 3 trial (NCT05085366) was a randomized, observer-blind, placebo-controlled study that enrolled approximately 7,500 women aged 16-40 years from approximately 300 sites across 13 countries, representing the largest trial assessing the efficacy of a CMV vaccine to date. Vaccine efficacy against primary CMV infection in healthy women was well below the company's target, ranging from 6% to 23% depending on the case definition used.
"Today's announcement is disappointing for families and healthcare professionals who have been eagerly awaiting a CMV vaccine to prevent congenital CMV, a leading infectious cause of birth defects," said Stéphane Bancel, Chief Executive Officer of Moderna.
Clinical Significance and Unmet Need
Congenital CMV represents a significant unmet medical need as a leading cause of infectious birth defects. Despite decades of effort across multiple vaccine technologies, no effective CMV vaccine has been successfully developed. The unique challenge of this trial was its aim to prevent primary infection from a latent virus, rather than preventing symptomatic disease, making it distinct from other vaccine approaches.
"We are clearly disappointed by the failure to prevent primary infection because it means there is still no vaccine for the prevention of congenital CMV despite the many decades of work by the field," said Stephen Hoge, MD, President of Moderna.
Continued Development in Alternative Indication
While discontinuing the congenital CMV program, Moderna will continue to explore the potential of mRNA-1647 to suppress disease associated with CMV reactivation in high-risk patients. The company is proceeding with an ongoing Phase 2 study evaluating the vaccine in bone marrow transplant patients, where CMV reactivation poses significant clinical risks.
Portfolio Impact and Financial Outlook
The CMV vaccine failure represents a setback in Moderna's diversification strategy beyond COVID-19 vaccines. The company had prioritized development of 10 additional investigational products following the pandemic, with eight of the 11 prioritized products having already achieved proof of concept or approval. The CMV vaccine would have been the ninth successful candidate.
Moderna emphasized that it does not anticipate any impact to its 2025 financial guidance or expectation of achieving breakeven in 2028. The company had anticipated minimal initial revenue contribution from mRNA-1647 given necessary investments in market building and launch, expecting the product to be cash-flow negative in 2028.
Scientific Contribution and Future Outlook
Despite the clinical failure, Moderna plans to share the complete trial results with the scientific community. The majority of data from the trial remains forthcoming, and the company hopes its learnings will contribute to continued pursuit of an effective CMV vaccine by the broader research community.
The company maintains that there is minimal read-through to its broader mRNA platform, including other latent virus programs, as this trial was unique in having prevention of primary infection as a primary endpoint. Moderna continues to await results from other pipeline candidates, including mRNA-4359 for cancer immunotherapy and mRNA-1403 for norovirus prevention.
