Cytomegalovirus Vaccine Candidate Heads to Phase 2 Study

A Massacutists based biotech company announced positive data from the 3-month interim analysis of safety and immunogenicity of the Phase 1 clinical study of its investigational vaccine mRNA-1647, which treats cytomegalovirus (CMV).

Moderna Inc.’s mRNA-1647 is a 2-antigen vaccine designed to protect against CMV infection. It combines 6 mRNAs in a proprietary lipid nanoparticle (LNP) in a single vial and encodes for 2 immuno-dominant proteins of CMV.

This phase 1 study reported:

In seronegative participants

A dose-related increase in neutralizing antibody titers was observed in both epithelial cell and fibroblast assays.

In epithelial cells, after the second vaccination, neutralizing antibody titers were 3 to 5 times higher than CMV-seropositive baseline titers at the 90 and 180 µg dose levels.

In fibroblasts, after the second vaccination, neutralizing antibody titers were equivalent to CMV-seropositive baseline titers at the 90 and 180 µg dose levels.

For the 12 sentinel participants who received mRNA-1647 under an earlier arm of the protocol (Phase A) and who received three doses (at 0, 2 and 6 months), neutralizing antibody titers were further boosted at 7 months and were sustained at or above CMV-seropositive baseline levels for at least 12 months.

In seropositive participants

A dose-related increase in neutralizing antibody titers was observed in both epithelial cell and fibroblast assays.

In epithelial cells, the second vaccination boosted neutralizing antibody titers to a level of 10-fold to 19-fold baseline titers in all dose groups.

In fibroblasts, the second vaccination boosted neutralizing antibody titers to a level of 2-fold to 4-fold baseline titers in all dose groups.

Based on this new data, Moderna Inc., said in a September 12, 2019, press release, ‘it is advancing mRNA-1647 to a dose-confirmation Phase 2 study in the near term.’

And, ‘preparation has also begun for a pivotal Phase 3 study designed to evaluate the efficacy of mRNA-1647 against primary CMV infection.’

This is good news since CMV is the most common infectious cause of birth defects in the USA, and there is not a preventive vaccine available today.

“The Moderna research, development and manufacturing teams have been working to ensure this program can transition in the near term to a dose-confirmation Phase 2 study, while also preparing for a pivotal Phase 3 study with the goal of ensuring commercial readiness,” said Stéphane Bancel, Moderna’s chief executive officer.

The Phase 2 study will test the intended Phase 3 formulation, which contains the same proprietary LNP used in this Phase 1 study.

“I am very encouraged by the ability of mRNA-1647 to induce high levels of durable immune responses that can reach or exceed the levels generated by natural CMV infection,” said Tal Zaks, M.D., Ph.D., chief medical officer at Moderna. 

“We recognize there is an urgent need for a preventative vaccine against congenital CMV and will be advancing mRNA-1647 into a Phase 2 study in the near term to confirm the appropriate dose, while we plan for a pivotal Phase 3 study.”

“Cytomegalovirus is the leading infectious cause of birth defects, and there is a great need for a vaccine that blocks transmission of the virus from the mother to the fetus,” said Sallie Permar, M.D., Ph.D., associate dean of physician-scientist development and professor of pediatrics, immunology, and molecular genetics and microbiology at Duke Medical School. 

“These interim data are exciting because mRNA-1647 has shown the ability to induce immune responses in seronegative individuals that are greater than what is seen in those naturally infected with CMV, which is important in that natural immunity is not completely protective against congenital CMV transmission.”

CMV is a common pathogen and member of the herpesvirus family. CMV is a common virus that infects people of all ages. Over half of adults by age 40 have been infected with CMV, says the Centers for Disease Control and Prevention (CDC).

Most people infected with CMV show no signs or symptoms. 

But, when a baby is born with a CMV infection, it is called congenital CMV. 

About 1 out of every 200 babies is born with congenital CMV infection. About 20 percent of babies with congenital CMV infection will have long-term health problems.

Congenital CMV infection results when infected mothers transmit the virus to their unborn child.

CMV is spread through saliva, mucus, and urine and is common in healthy babies and toddlers; as a result, young children can be a major source of infection for pregnant women, particularly mothers, daycare workers, preschool teachers, therapists, and nurses, said the Company.

Moderna, Inc. is advancing messenger RNA (mRNA) science to create a new class of transformative medicines for patients. mRNA medicines are designed to direct the body’s cells to produce intracellular, membrane or secreted proteins that can have a therapeutic or preventive benefit and have the potential to address a broad spectrum of diseases. 

Published by Precision Vaccinations