Trial Updates from Moderna’s mRNA, RSV Vaccine Candidates

Moderna recently announced Phase 1 data updates for its RSV vaccine candidate and new seven-month interim Phase 2 data regarding its cytomegalovirus (CMV) vaccine candidate. 

Researchers stated that in a Phase 1 study of its RSV vaccine, mRNA-1345, a single dose vaccination of 50 micrograms or 100 micrograms of the vaccine was generally well-tolerated in younger adults.

Additionally, mRNA-1345 increased RSV neutralizing antibodies in seropositive younger adults.

The most common adverse events were minor, such as injection site pain, headache, fatigue, and myalgia. These adverse events generally occurred one to three days post-vaccination and resolved in one to four days. 

Notably, there were no deaths. The study is ongoing and all four cohorts are fully enrolled. 

mRNA-1345 is an RSV vaccine for a prefusion F glycoprotein, which elicits antibody responses compared to the postfusion state, a Moderna spokesperson said. 

Moderna will invest resources and continue to leverage its mRNA platform to accelerate the development of its mRNA vaccine pipeline. 

“We will continue to pursue RSV vaccines to protect the most vulnerable populations – young children and older adults – where reducing RSV infection is also a significant unmet need. We will also be evaluating possible combinations of mRNA-1345 with other respiratory virus vaccines,” Jacqueline Miller, MD, senior vice president of infectious diseases at Moderna, said in the announcement.

Moderna’s mRNA-1647 vaccine combines six mRNAs in a single vial.

Additionally, a Phase 2 study found that mRNA-1647 at 50 micrograms, 100 micrograms, and 150 micrograms was generally well-tolerated in the study population. The most common solicited adverse reaction was injection site pain, headache, fatigue, myalgia, arthralgia, and chills. 

Neutralizing antibody geometric mean titers (GMTs) against epithelial cell infection were about 20-fold higher in CMV-seronegative participants after the third vaccination compared to the baseline GMT of the CMV-seropositive group, a Moderna spokesperson said.

Meanwhile, neutralizing antibodies GMTs against epithelial cell infection increased to at least 6.8 fold over baseline among CMV-positive participants after the third vaccination. 

And neutralizing antibody GMTs against fibroblast infection increased to approximately 2-fold over baseline. 

Based on results from the trial, the 100-microgram dose has been chosen for the Phase 3 pivotal study, which will evaluate the prevention of primary CMV infection in seronegative women aged 16 to 40 years. 

Moderna’s mRNA-1644 is a novel approach to HIV vaccine strategy in humans that is designed to elicit neutralizing HIV-1 antibodies (bNAbs). Currently, the strategy is being developed in collaboration with the International AIDS Vaccine Initiative (IAVI) and the Bill and Melinda Gates Foundation (BMGF). 

A Phase 1 study for mRNA-1644 will use human testing to validate the approach and antigens, and multiple novel antigens will be used for germline-targeting and immuno-focusing. 

A second approach for mRNA-1547 is being evaluated in collaboration with the National Institutes of Health (NIH) and includes various native-like trimer antigens. Moderna stated that it expects to begin Phase 1 clinical trials for both mRNA-1644 and mRNA-1574 in 2021.

To date, Moderna has entered 14 different mRNA vaccine candidates into clinical trials. Most notable is its mRNA-based vaccine for COVID-19.

Clinical data demonstrate that the company’s proprietary vaccine technology has been generally well-tolerated and can elicit durable immune responses to viral antigens.

In the near future, Moderna said it will explore potential combination vaccines against the flu, SARS-CoV-2, RSV, and human metapneumovirus. 

The company’s first-generation flu program will evaluate multiple candidates comprising multiple antigen combinations against various viruses. The Phase 1 clinical trial for the program will begin this year. 

“We believe we have a unique opportunity to develop new vaccines against viruses hurting people around the world, at a pace that is radically different from what the industry has previously done,” said Stéphane Bancel, chief executive officer of Moderna. 

“We are working to further increase our vaccine pipeline and accelerate these important programs. With our mRNA vaccines, we believe we have an opportunity to have a profound impact on human health,” Bancel continued.