Following the success of messenger RNA (mRNA) vaccines in Covid-19, there has been a surge of investment in new trials. Recent positive clinical studies in melanoma and respiratory syncytial virus (RSV) have now shown that mRNA vaccines could prove effective beyond treating Covid-19, and the pharma world has taken note.
In 2023, four major trials in influenza, genital herpes, and melanoma will show just how far-reaching mRNA vaccine technology could be. These include Moderna’s mRNA-1010 and Pfizer’s modRNA vaccine in seasonal influenza, Roche/BioNTech’s RO7198457 in advanced melanoma, and BioNTech’s BNT-163 for lesions in genital herpes.
Although most early clinical research into mRNA vaccines was dominated by institutions and government agencies, the tables have quickly turned. “mRNA technology is new and successful, and it looks like it’s going to be the next big breakthrough,” says Dr. Harvey Friedman, University of Pennsylvania, who is researching mRNA vaccines for herpes. “The major pharma companies don't want to be left out of this technology.”
In 2023, 85% of planned mRNA vaccine trials are sponsored by industry, up from just 34% of mRNA trials initiated in 2021, according to GlobalData’s clinical trials database. Meanwhile, overall investment in mRNA vaccine trials has surged in the last decade. GlobalData is the parent company of Clinical Trials Arena.
mRNA vaccines work by providing cells with instructions to encode specific proteins, which can then prevent infections by eliciting an immune response or treating other disease states. As industry accelerates its shift into mRNA vaccines, all eyes are focused on these four trial readouts expected in 2023.
Pfizer and Moderna eye seasonal influenza
The two largest mRNA vaccine trials with readouts in 2023 are for seasonal influenza. First up, Moderna’s 6,102-patient, Phase III trial of mRNA-1010 (NCT05415462) has immunogenicity data expected in Q1 2023. The trial is testing mRNA-1010 against an active comparator vaccine, with primary endpoints focused on antibody titer levels and adverse events (AEs).
Next up, Pfizer’s 36,200-patient, Phase III trial of its quadrivalent modRNA influenza vaccine (NCT05540522) has results expected in 2023. The primary endpoints measure incidence of laboratory-confirmed influenza cases, levels of antibody titers, and AEs—all compared to an active vaccine comparator.
These two vaccine trials come after recent influenza seasons have proven to be uncharacteristically long. Meanwhile, some clinicians are still holding out hope for widespread influenza and Covid-19 combination vaccines.
mRNA vaccine trials for cancer
In the melanoma space, two major players have mRNA vaccine candidates at the Phase II stage: Moderna/Merck & Co’s mRNA-4157 and Roche/BioNTech’s RO7198457 (autogene cevumeran). In December 2022, Moderna and Merck & Co announced positive topline for the Phase IIb KEYNOTE-942 trial (NCT03897881), which tested mRNA-45157/V940 alongside Keytruda (pembrolizumab) as an adjuvant therapy following complete tumor resection in advanced-stage melanoma. The two companies have said they plan to initiate a Phase III trial in 2023.
Meanwhile, Roche and BioNTech are looking to follow suit with their own study in melanoma. The 131-patient, Phase II IMCODE101 trial (NCT03815058), which tests RO7198457 and Keytruda against Keytruda alone, has results expected in 2023. As a primary endpoint, the open-label study measures progression free survival (PFS) over 24 months for patients with previously untreated advanced melanoma.
BioNTech targets herpes
BioNTech is also testing the mRNA approach with a vaccine to prevent genital herpes lesions. The 108-participant, Phase I study of BNT163 (NCT05432583), which tests the vaccine’s safety and immunogenicity, has data expected in H2 2023.
The herpes virus has more than 70 proteins, which can make it challenging to choose the right mRNA targets, explains Friedman, who works on BNT163 development. “So far, our choice of targets looks great in mice and it looks great in guinea pigs,” he says. “Now let's see if it looks great in humans.”
Meanwhile, Moderna has joined the race to develop an mRNA vaccine for herpes, expanding its own mRNA pipeline with a vaccine against herpes complex virus 2 (HSV-2).
The next generation of mRNA vaccines
As pharma looks toward these four major mRNA vaccine trial readouts in 2023, the overall field remains largely focused on infectious diseases. Among all ongoing mRNA vaccine trials, 70% are in the infectious disease space, according to GlobalData’s clinical trials database. Oncology is the next most common therapy area, representing 12% of all ongoing mRNA vaccine studies.
With more key mRNA trial results in melanoma around the corner, time will tell whether mRNA vaccine technology will take a strong hold in the cancer drug development space. In the meantime, mRNA vaccines will likely continue to make strides in combating infectious diseases.
Cell & Gene Therapy coverage on Clinical Trials Arena is supported by Cytiva.
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