Issue:March 2024

DRUG DEVELOPMENT EXECUTIVE - Thermo Fisher Scientific: What to Expect From the Next Wave of RNA-Based Therapeutics

The emergence of mRNA vaccines during the COVID-19 pandemic propelled this innovative technology to the forefront of medical advancement. As we usher in the next era of RNA-based therapeutics, RNA’s potential extends far beyond COVID-19, promising groundbreaking treatments for cancer, metabolic diseases, and a range of other infectious diseases. To meet growing demand and to bring new RNA treatments successfully to market at scale, developers and manufacturers must embrace best practices to overcome potential obstacles.

Drug Development & Delivery recently had a discussion with Dr. Dale Patterson, Vice President and General Manager, Molecular Biology at Thermo Fisher Scientific, to delve into the world of RNA therapies and understand their next act beyond COVID-19.

Q: While mRNA garnered significant public attention during the COVID-19 pandemic, researchers have been exploring the clinical use of RNA for years. What does the current landscape for RNA-based vaccines and therapeutics look like?

A: mRNA (messenger ribonucleic acid) became a household name during the COVID-19 pandemic, and for good reason. Innovative mRNA-based vaccines developed with unprecedented speed played a key role in curbing the spread of the virus and protecting individuals from severe infection. However, these vaccines are only the tip of the iceberg when it comes to the many clinical possibilities for mRNA and other categories of RNA therapeutics, including RNA interference (RNAi), RNA aptamers, and other therapies, such as antisense oligonucleotides (ASOs), which have the highest number of currently approved treatments. RNA-based therapeutics are unique in they address disease at the source, opening the door for improved, safer, and more effective treatment options for diseases ranging from cancer to chronic conditions like diabetes.

Drug developers are rapidly taking notice of the many clinical possibilities for RNA-based therapies and vaccines. According to GlobalData, the market for mRNA-based oncology therapies is expected to reach $2 billion by 2029. Today, there are 90+ mRNA-based drug candidates in clinical trials with at least a dozen drugs in development using other types of RNA. What’s exciting is how quickly we are seeing mRNA and other RNA-based therapeutics make it into the clinical phase compared to the timeline we’ve seen for other biotherapeutics.

Q: Can you explain how mRNA vaccine development differs from the approach taken with traditional vaccines?

A: Given the eradication of diseases like smallpox and polio, the impact of traditional vaccines on human health cannot be minimized. Still, mRNA-based vaccines hold significant promise and have been shown to have greater specificity and efficacy than traditional vaccines. The world saw one of the most obvious differences between mRNA and traditional vaccines firsthand during the COVID-19 pandemic. As they do not contain a weakened or inactivated virus and can be developed with a platform process that does not require the use of cells, mRNA-based vaccines can be developed and manufactured much more quickly. This makes them an ideal defense against new infectious diseases or variants. In addition to speed, the process to develop mRNA vaccines is overall much simpler and more cost-effective with fewer steps required. Furthermore, the footprint required to scale production and make a significant amount of mRNA vaccines is far less than what would be required with traditional vaccines.

Q: What should developers keep in mind during the early stages of mRNA vaccine or therapeutic development?

A: Regardless of how new they are to the mRNA space, there are some best practices developers should keep in mind as they set out to develop new mRNA vaccines or therapeutics. First, developers should be mindful about choosing high-quality raw materials optimized for the needs of their project. This is one of the earliest steps in the mRNA development process, and choosing right can pay dividends down the line. Selecting materials solely based on cost without being mindful of future quality and regulatory requirements could impact your long-term success and limit the scalability of your product later. The raw materials you select should meet your project’s needs for quality and documentation, regulatory support, and scalability as you move closer to commercialization.

Q: How can developers work to ensure the scalability of their mRNA-based vaccines and therapeutics?

A: As previously discussed, choosing the right raw materials at the start is a key factor in ensuring the scalability of your mRNA products. Additionally, developers should do their due diligence when selecting suppliers. When it comes to scalability, it’s important to select an experienced supplier that can scale with your project. Remember to ask key questions, such as whether they have an established track record of partnering with developers who have commercialized new therapies or if they have a contingency plan in case of shortages.

For this next wave of mRNA-based vaccines and therapeutics, it’s important to not just be able to scale up but to be able to scale down. For example, personalized cancer vaccines using mRNA are in development now for incredibly small patient populations. That means manufacturing these vaccines won’t need to be scaled nearly to the extent that the COVID-19 vaccines were. In fact, being able to scale down manufacturing and potentially make these vaccines on-demand will be most cost-effective. At Thermo Fisher, one of our offerings is technology that essentially allows these therapeutics to be manufactured at the same quality as they would be in a large bioreactor but at a smaller scale. Overall, when it comes to scalability, developers should think about what will be needed to manufacture these new drugs for smaller populations to ensure they are accessible.

Q: Now that the spotlight is on mRNA, what are your predictions for the future of this field?

A: With so many mRNA therapeutics currently in development, the next 3 to 5 years will likely see an explosion in the number of mRNA drugs approved, including therapeutics and vaccines for some of the most difficult-to-treat or intractable diseases and conditions. mRNA has capabilities that other types of therapeutics lack and can target and attack disease at the cellular level, unlocking new potential strategies for treating diseases like cancer or rare, genetic conditions. Additionally, as mRNA therapeutics and vaccines are approved throughout the next few years, this may help speed up the approval process for other drugs in the pipeline by offering new pathways and precedents for regulators, such as the US FDA. We are at a turning point for the use of mRNA as a new, flexible way to treat so many different diseases. It will be exciting to see other developers join the mRNA wave and explore new and broader applications.

Q: Thermo Fisher and Moderna announced a 15-year mRNA manufacturing deal in February 2022. What can you tell us about Thermo Fisher’s approach to collaborating with companies in this space?

A: As we saw during the COVID-19 pandemic, the speed at which mRNA vaccines were brought to the public was due in part to strong collaborations between developers and manufacturers. BioNTech, a leading player in the mRNA market, partnered with Pfizer – a large pharmaceutical company with plenty of experience bringing vaccines to market at scale. Moderna, on the other hand, worked with various CDMOs, including Thermo Fisher, to scale its manufacturing process to ensure its vaccine could reach the global community.

At Thermo Fisher, we have a unique approach to collaboration and offer developers pathways to build or buy. We have a complete end-to-end product portfolio, and developers can choose to collaborate with us at just one stage of the development or manufacturing process or from beginning to end. Additionally, we offer services to support developers from early stage emerging startups to large pharmaceutical companies. When it comes to this new era for RNA-based therapeutics, we are committed to working closely with developers and sharing knowledge to bring these innovative treatments to patients more quickly.