Research & Development
Moderna Touts Additional Positive Phase 1 Data from Cytomegalovirus Vaccine (mRNA-1647) and First Participant Dosed in Phase 2 Study
14 January 2020 - - US-based biotechnology company Moderna, Inc., (NASDAQ: MRNA) has received positive seven-month interim safety and immunogenicity data after the third and final vaccination in the Phase 1 study of its investigational cytomegalovirus vaccine (mRNA-1647), the company said.

The findings build on the previously reported three-month interim analysis, after two vaccinations, announced at the company's R and D Day in September 2019.

Additionally, the company announced that the first participant was dosed in the Phase 2 dose-confirmation study. mRNA-1647 is a wholly owned program in Moderna's prophylactic vaccines portfolio.

mRNA-1647 comprises six mRNAs encoding two antigens in one vaccine, and is designed to protect against CMV infection.

Of the 6m RNAs, five encode the subunits of the CMV pentamer complex and one mRNA encodes the glycoprotein B protein, both of which are highly immunogenic.

Both pentamer and gB proteins are essential for CMV to enter epithelial cells, which is the first step in CMV infection. mRNA-1647 is designed to produce an immune response to both pentamer and gB antigens to prevent CMV infection.

The second interim analysis of the Phase 1 trial reports safety and immunogenicity of the first three dose levels (30, 90 and 180 µg) through seven months (one month after the third vaccination) and the highest dose level (300 µg) through three months (one month after the second vaccination).

Neutralizing antibody titers were assessed in two assays utilizing epithelial cells and fibroblasts, which measure immune response to pentamer and gB antigens, respectively.

Safety data were consistent with those reported at the three-month interim analysis. The vaccine was generally well-tolerated and there were no vaccine-related serious adverse events.

The most common solicited local adverse reaction across all vaccinations was injection site pain (54-100% of a given treatment group). The most common solicited systemic ARs reported overall were headache, fatigue, myalgia and chills.

Fever was reported in 0-55% of CMV-seronegative treatment groups and in 8-67% of CMV-seropositive treatment groups. The most common Grade 3 solicited ARs were in CMV-seropositive participants, and were fatigue (0-27% of a given treatment group), chills (0-27% of a given treatment group) and fever (0-33% of a given treatment group).

In general, the highest solicited systemic AR rates were reported after the second vaccination, were more frequent in the CMV-seropositive compared to the CMV-seronegative group, and tended to correlate to dose.

As reported in the previous interim analysis, one related Grade 4 adverse event has been observed, which was an isolated lab finding of elevated partial thromboplastin time, which was elevated at baseline (Grade 1) and self-resolved on the next lab test with no associated clinical findings.

CMV is spread through saliva, breastmilk, 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.

Efforts to create a vaccine began in the 1970s, and in 1999 the Institute of Medicine (now National Academy of Medicine) designated CMV as a "highest priority" category for vaccine development.

Prior studies of investigational vaccines that did not protect against the CMV pentamer antigen demonstrated limited efficacy against CMV infection and limited durability of immune response.

Moderna scientists designed the company's prophylactic vaccines modality to prevent or control infectious diseases. This modality now includes seven programmes, all of which are vaccines against viruses.

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.

Moderna currently has five development candidates for potential commercial uses in this modality, including: respiratory syncytial virus vaccine (mRNA-1777 and mRNA-1172 or V172 with Merck (NYSE: MRK)), cytomegalovirus vaccine (mRNA-1647), human metapneumovirus and parainfluenza virus type 3 (hMPV+PIV3) vaccine (mRNA-1653) and Zika vaccine (mRNA-1893) with the Biomedical Advanced Research and Development Authority (BARDA).

Three development candidates in this modality are available for potential global health uses including: influenza H10N8 vaccine (mRNA-1440), influenza H7N9 vaccine (mRNA-1851) and chikungunya vaccine (mRNA-1388) with the Defense Advanced Research Projects Agency (DARPA).

To date, Moderna has demonstrated positive Phase 1 data readouts for six prophylactic vaccines (H10N8, H7N9, RSV, chikungunya virus, hMPV+PIV3 and CMV). Moderna's investigational Zika vaccine (mRNA-1893), currently in a Phase 1 study, was recently granted FDA Fast Track designation.
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