Massachusetts-based biotechnology company Moderna, Inc. (Nasdaq: MRNA) has announced the completion of enrollment for its Phase 2 clinical trial evaluating the immunogenicity and safety of cytomegalovirus (CMV) vaccine mRNA-1647. This follows the announcement of positive Phase 1 clinical trial results in January, which provided data for three participant dose cohorts after a third and final vaccination. According to the press release, an interim analysis for the Phase 2 trial is expected to be available in the third quarter of 2020.
Chief Executive Officer Stéphane Bancel stated, “I would like to thank the dedicated Moderna CMV team and our partners at clinical trial sites for their support in completing enrollment of the Phase 2 study ahead of plan. We recognize the urgent need for a preventative vaccine against CMV in women of childbearing age, which we believe positions our wholly owned mRNA-1647 program as a potential blockbuster commercial and clinical opportunity. We believe our CMV vaccine will build Moderna’s future and embodies our mission of creating a new generation of transformative medicines for patients. The Moderna team is working diligently to start the Phase 3 study in 2021.”
The mRNA-1647 vaccine, which is designed to promote an immune response against components of the virus essential for infecting human cells, consists of six mRNAs that encode two virus-associated antigens. One of the mRNAs encodes the envelope protein glycoprotein B (gB), which is expressed on the surface of the virus. gB is involved in mediating the entry of the virus into cells and in the spread of the virus from cell-to-cell. Five of the six mRNAs encode CMV pentamer complex subunits, which are also important for the entry of the virus into cells and targeted by the majority of neutralizing antibody during the anti-viral immune response.
Both glycoprotein B and the pentamer complex subunits are highly immunogenic, meaning that the immune system can generate a powerful response against these components and therefore protect against CMV infection. Currently, there is no approved CMV vaccine.
The Phase 2 clinical trial will involve the administration of vaccine to 252 healthy adults in the United States, including both CMV-seronegative and CMV-seropositive individuals, at three dose levels (50, 100, and 150 micrograms) at three time points over the course of six months (0, 2, and 6 months).
At three months (one month after the administration of the second dose), the company will provide an interim analysis of the trial which will support preparation for a Phase 3 trial that is expected to be initiated in 2021. According to the press release, the Phase 3 clinical trial “will evaluate prevention of primary CMV infection in a population that includes women of childbearing age.”
Moderna provided insight into plans for its Phase 3 study in the recent press release. “The Company is actively preparing for a global randomized, observer-blind, placebo-controlled Phase 3 pivotal study to evaluate the efficacy of mRNA-1647 against primary CMV infection. Moderna has solicited and received Type C meeting feedback from the FDA on the preliminary design of the pivotal trial, which will evaluate prevention of primary CMV infection in a population that includes women of childbearing age.”
“The Company believes this can be achieved with a trial with no more than 8,000 participants and feasibility assessments of study sites has already begun across North America and Europe. After the Phase 2 three-month data are analyzed, which is expected in the third quarter of 2020, these data will inform the dose selection for the Phase 3 pivotal study. The pivotal trial design will be finalized after discussion with the FDA and other global health authorities. Manufacturing and planning are already underway for this pivotal study, which is expected to start in 2021.”
In addition to the CMV vaccine, Moderna is developing vaccine candidates against other prevalent infectious agents including the Epstein-Barr virus (EBV), Zika virus, respiratory syncytial virus (RSV), influenza H7N9, and the novel coronavirus (SARS-CoV-2). The US Food and Drug Administration (FDA) granted Fast Track designation to the Zika vaccine, which is currently being evaluated in a Phase 1 clinical trial.
According to Moderna, “The potential advantages of an mRNA approach to prophylactic vaccines include the ability to mimic natural infection to stimulate a more potent immune response, combining multiple mRNAs into a single vaccine, rapid discovery to respond to emerging pandemic threats and manufacturing agility derived from the platform nature of mRNA vaccine design and production.”
The herpesvirus CMV naturally infects humans and moneys and has the characteristic ability to persist latently within the body for extended periods of time. The virus, which is normally transmitted through contact, saliva, and urine, and can be transmitted from infected mothers to their unborn children, impacts 25,000 newborns in the United States each year and is the leading infectious cause of birth defects in the country, resulting in a variety of neurodevelopmental abnormalities from vision problems to hearing loss.
In March 2013, Moderna signed a contract with AstraZeneca for the discovery, development, and commercialization of mRNA therapeutics for the treatment of diseases associated with metabolism, kidneys, the cardiovascular system, and cancer. In January 2020, the National Institute of Allergy and Infectious Disease (NIAID) partnered with Moderna to develop a vaccine against the virus that causes COVID-19.