Moderna has announced it will discontinue its congenital cytomegalovirus (cCMV) vaccine clinical development program.
Mr Stephane Bancel, Moderna CEO, said the study did not meet its primary efficacy endpoint of preventing CMV infection in seronegative female participants of childbearing age (16-40 years).
CMV is a leading cause of birth defects, hearing loss, and neurodevelopmental disability.
“Of course, this outcome is disappointing for families and healthcare professionals who have been eagerly awaiting a vaccine to prevent congenital CMV, a leading cause of infectious birth defects,” Bancel said.
“The majority of the data from this trial is still forthcoming, and we will share our full results with the scientific community in hopes that our learnings can contribute to the continued pursuit of a congenital CMV vaccine.”
He said CMV had long been one of the most difficult vaccine targets. Despite decades of effort across multiple vaccine technologies, no one had yet developed an effective vaccine.
“This study for mRNA-1647 was particularly challenging in that it was aiming to prevent primary infection from a latent virus, rather than preventing symptomatic disease,” he said.
“This makes this trial unique in our pipeline; it was the only clinical trial in which the prevention of primary infection was a primary endpoint. We believe there is minimal read-through to the broader platform, including other latent viruses
Bancel said Moderna was disappointed by the failure to prevent primary infection because it meant there is still no vaccine for the prevention of congenital CMV despite the many decades of work by the field.
“CMV does cause significant disease in other contexts, including reactivation of the latent virus in those undergoing bone marrow transplantation, and we will continue to explore the potential of mRNA-1647 to suppress disease associated with reactivation in those high-risk patients through our ongoing phase two study,” he said.
“I am tremendously grateful for our dedicated team, our partners at clinical trial sites, and all the trial participants who made this research possible. We are proud to have tried to develop a vaccine for congenital CMV given the unmet medical need.
“Our work on mRNA-1647 has deepened scientific understanding of this complex virus and advanced what’s possible with mRNA science.”
Advanced understanding of virus
The National CMV Foundation in the US said it was a disappointment for the field of CMV vaccine research and prevention.
“We extend our deep gratitude to Moderna for its vision, commitment, and courage in taking on this challenge,” the foundation said. “Their leadership in advancing CMV vaccine development and their ongoing partnership in advocacy have brought much-needed attention to a virus that affects tens of thousands of infants and families each year.
“Their efforts have moved the field forward in meaningful ways, even as we await detailed data from this trial to inform the next generation of vaccine candidates.”
Dr Mark Schleiss, Professor of Paediatric Infectious Diseases at the University of Minnesota and director of the foundation’s scientific advisory committee, said Moderna deserved credit for its transparency in sharing the results of a successfully completed phase three study, a substantial accomplishment.
“Additional data analysis will inform and direct future vaccine studies, which are needed,” he said. “In the meantime, we must remember that we have many tools that can help prevent cCMV infection. Women of childbearing age can talk to their doctors, learn about prevention, recognise risk factors, and ask about screening.
“Promoting education about the risks of CMV in pregnancy, all of these approaches will help reduce cCMV, even as vaccine research continues.”
Dr Sallie Permar, chair of the Department of Paediatrics at Weill Cornell Medical School, said while the outcome was a setback, it further informed understanding of immune protection against the virus
“Science moves forward through both success and failure, and this is why continued investment in research, and in building the pipeline of scientists committed to understanding and preventing CMV, is essential,” she said.
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