The mRNA technology behind the COVID-19 vaccines has made strides in the field of medicine, showcasing the enormous potential of mRNA as an innovative and versatile platform for developing vaccines and other therapeutic applications.
by Dr Jane Leong
In the wake of the COVID-19 outbreak, experts raced to find ways to combat the highly contagious SARS-CoV-2 virus. When the US Food and Drug Administration (FDA) first authorised the emergency use of two innovative messenger ribonucleic acid (mRNA) vaccines for the prevention of COVID-19 at the end of 2020, mRNA technology quickly emerged from obscurity to become a beacon of hope in the fight against a deadly enemy that was causing a significant number of deaths and morbidity around the world. 1,2
Two years later, Moderna continues to explore the immense potential of mRNA technology. Significant progress has been made in multiple disease areas beyond COVID-19, with a range of mRNA-based therapeutics currently undergoing various stages of clinical trials. Notably, mRNA therapeutics may be the new frontier in the management of other non-COVID-19 respiratory diseases and cancer, among other things. 3,4
mRNA Technology – A Breakthrough in Modern Medicine
The flexibility of mRNA technology is revolutionising the landscape of medicine as we know it. This cutting-edge technology harnesses the information code in mRNA molecules to make proteins encoded in the mRNA vaccine or therapeutic agent, using the cell’s own natural machinery for this process, offering a promising approach for preventing infectious diseases and treating a range of diseases.5
The development of mRNA-based therapeutics has accelerated over the past decade, culminating in the recent success of the widely used mRNA COVID-19 vaccines. These vaccines have demonstrated efficacy in preventing severe COVID-19 disease and hospitalisations and have made a major contribution to the fight against the global pandemic. With its rapid development and impressive results, mRNA technology has attracted global attention and significant interest from researchers and clinicians alike.5
More Than Just a Weapon Against COVID-19
mRNA technology has allowed mRNA COVID-19 vaccines to be rapidly adapted to address emerging viral strains. Bivalent mRNA COVID-19 boosters containing antigens from Omicron variants already offer enhanced immune responses against a broad range of SARS-CoV-2 strains compared to vaccines that contain only the original strain.6 In the future, it can be expected that mRNA vaccines will continue to be updated with emerging strains as the disease evolves.7 This flexibility will be crucial in the face of the ongoing challenges of COVID-19 and potentially other respiratory viruses.8
The use of mRNA vaccines can also be considered for other respiratory infections, particularly those that may cause considerable morbidity and mortality among the young, immunocompromised, and elderly populations. Once we have vaccines available that can target three of the most important seasonal respiratory viruses, the next challenge will be ensuring these vaccines reach the people who need them. Current awareness of vaccination is high following the pandemic; however, the influence of vaccine hesitancy and fatigue cannot be underestimated. The development of combination mRNA vaccines that target multiple respiratory pathogens, such as Moderna’s combined investigational COVID-19/influenza/respiratory syncytial virus (RSV) candidate (mRNA-1230), can help to streamline vaccination efforts and reduce the need for multiple injections, making it more convenient for individuals and healthcare providers and increasing vaccine uptake among the public.9,10
Specific to RSV, vulnerable individuals are particularly at risk of infection owing to the lack of approved vaccines against the virus. On this front, Moderna’s mRNA-based vaccine candidate (mRNA-1345) was granted Breakthrough Therapy Designation (BTD) in early 2023 by the US FDA to prevent RSV-associated lower respiratory tract disease in adults aged 60 years or older.3 This is an important milestone, as RSV vaccine development is a long-term public health objective.11
Changing the Game for Cancer Care
Unlike vaccines for infectious diseases, mRNA-based therapeutics for cancer, also known as individualised neoantigen therapy (INT), are focused on the treatment of the disease rather than prevention.12 mRNA-based cancer therapies have shown encouraging results when used in conjunction with the current standard of care for melanoma.12,13 In an ongoing randomised, open-label, phase 2b trial for Moderna’s investigational INT, mRNA-4157 (V940), used in combination with Merck’s pembrolizumab (an anti-programmed death receptor-1 therapy), significantly improved recurrence-free survival and reduced the risk of recurrence or death by 44% compared with pembrolizumab alone.14
Based on the study, the US FDA and European Medicines Agency have granted BTD and Priority Medicines Scheme designations, respectively, for mRNA-4157 (V940) in combination with pembrolizumab for the adjuvant treatment of patients with high-risk stage III/IV melanoma following complete resection.4,15 Phase 3 of the study is expected to commence within 2023 and include additional tumour types, such as non-small cell lung cancer.15
Moderna’s Pipeline of mRNA Vaccines
As of January 2023, Moderna has 48 programmes in development, including 36 currently in active clinical trials, and investment in research and development is expected to hit US$4.5 billion in 2023.16
In addition to developing mRNA vaccines for respiratory infections and cancer therapies, Moderna is also investigating mRNA-based vaccines for latent viruses.17 After an initial infection, latent viruses are not eliminated from the body; they stay present in a resting state and do not cause noticeable symptoms. However, they can reactivate and cause clinical symptoms, for example, when triggered by factors like stress or compromised immunity.
Of Moderna’s seven latent virus vaccine candidates, five are currently undergoing clinical trials, including vaccines for the human immunodeficiency virus (HIV) as well as viruses of the Herpesviridae family, such as Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Varicella-Zoster virus (VZV), and herpes simplex virus (HSV).17
Moderna’s commitment to improving health outcomes extends to diseases with a significant global burden. One notable vaccine candidate already undergoing a phase 1b clinical study is an mRNA vaccine for the treatment of heart failure. Additionally, vaccines against the Nipah and Zika viruses are currently in phase 1 and phase 2 studies, respectively.18 Determined not to leave anyone behind, Moderna is also studying mRNA vaccines against several rare diseases, with a potential vaccine candidate against propionic acidemia currently undergoing phase 1/2 trials.16
In April 2023, Moderna announced several exciting new developments during its 4th Vaccine Day, including the development of pentavalent and trivalent vaccines for norovirus, a highly contagious enteric virus and the leading cause of diarrheal disease globally. Furthermore, a candidate for treating Lyme disease was also a key highlight, as it represents the first application of Moderna’s mRNA technology against bacterial pathogens.19
Taking mRNA Technology Forward
Recent advances in mRNA technology have optimised the stability, structure, and delivery methods of mRNA-based vaccines.12 Moderna remains dedicated to exploring the potential of mRNA-based therapeutics through the innovative application of mRNA technology to push beyond the boundaries of modern medicine. We look forward to delivering exciting breakthroughs in this field that will improve health outcomes for patients worldwide. [APBN]
This article was first published in the June 2023 print version of Asia-Pacific Biotech News.
About the Author
Dr Jane Leong, Vice President, Medical Affairs Asia Pacific for Moderna
As Vice President, Medical Affairs for Moderna in Asia Pacific, Dr Leong is responsible for the development and implementation of medical strategies and activities for Moderna products in the region.
Dr Leong’s career of over 30 years spans clinical practice and the pharmaceutical industry in both vaccines and pharmaceuticals. Dr Leong has played a key role in launching several vaccines on the Australian National Immunization Program, including the roll out of the A/H1N1 pandemic vaccine in Australia and other countries and implementing global medical strategies for seasonal and pandemic influenza vaccines. Prior to joining the industry, Dr Leong practiced clinical medicine in family medicine clinics and hospitals.