8 perces olvasási idő 10 szept. 2021
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How mRNA medicines might change the drug landscape

8 perces olvasási idő 10 szept. 2021

The COVID-19 pandemic has put mRNA medicines on a fast track, creating significant opportunities as well as some challenges.

In brief
  • Cell and gene, and nucleic acid therapies, which target our genetic machinery, are having a renaissance.
  • As the rising star of nucleic acid therapies, the messenger RNA (mRNA) technology offers a multitude of opportunities to develop therapies beyond vaccines.
  • Still a novelty, mRNA technology will need to prove its mettle, either through scalable, ready-to-treat therapies, or highly personalized niche drugs.

More than a half-century after the theoretical discovery of genetic material manipulation, cell and gene and nucleic acid programs are in the midst of a therapeutic renaissance. Propelled by major science-technology-medicine advancements, the rise of these therapies that target our genetic machinery — such as gene replacement, correction or modulation — is affecting all the steps in the life sciences value chain.

The need for personalized medicines, specific requirements in product formulation and fill-and-finish, are currently creating infrastructure challenges for pharmaceutical manufacturing and supply chains. Furthermore, given the high cost of these new therapies, societal and economic impacts are demanding new approaches to market access, pricing and purchasing.

The class of nucleic acid-based therapies is diverse and can be grouped into four major clusters

Conventional small molecules and monoclonal antibodies continue to play a major role in modern pharmacotherapy. However, certain limitations remain, including adherence issues, challenges with personalization, lower curative potential, as well as a lack of universal applicability.

Nucleic acid-based platforms have the potential to unlock several therapeutic strategies with significant curative potential. Based on the primary therapeutic target and the mechanism of action, these nucleic acid-based therapies can be grouped into four clusters.

  1. Gene-modifying therapies: Gene-modifying therapies include chemical and cell-based guide RNA (gRNA), as well as cell-based plasmids. They can either alter or correct the native target gene, or introduce a missing gene, thereby cutting off the root of the disease.
  2. Gene expression modifiers: These therapies include antisense nucleotides, micro RNA (miRNA) and small interfering RNA (siRNA), which together are referred to as RNAi; and DNAzymes. Antisense nucleotides and RNAi gene therapeutics alter the upstream elements of our gene translation machinery. Whether binding directly to the target RNA or interacting first with RNA-induced silencing complexes, these therapies are designed to impede specific steps in the readout of active genes, turning off the “faucet” of the downstream undesired protein production. Meanwhile, by cleaving target nucleic acids, DNAzymes can down-regulate gene expression.
  3. Protein expression therapies: The messenger RNA (mRNA) technology transfers the encoded route for protein synthesis into the patient’s cells.
  4. Protein interaction modifiers: These are represented by nucleic acid aptamers. These intermediate-weight products (usually single-stranded oligonucleotides) have a predictable folding architecture and bind with high affinity and specificity to target proteins, altering their biological functions.

Based on the EY-Parthenon pipeline scan in early 2021, apart from the boiling gene therapy market, which already has six “ex vivo” and four “in vivo” approved therapies, ASO and RNAi form the most crowded phase three cluster. Hot on the heels of these modalities, however, are mRNA-based therapies.

Figure 1: Types of nucleic acid-based therapies
Nucleic acid therapy types -molecular species on nucleic acid therapies

mRNA becomes the rising star of nucleic acid therapy

After decades of research and the accumulation of theoretical knowledge, the COVID-19 pandemic has brought mRNA to the forefront as a new modality, and finally reached the tipping point in demonstrating its utility in infectious diseases.

Although complex, the technology is based on a relatively simple principle: mRNA vaccines, upon delivery, tell our cells to synthetize proteins, e.g., resembling those from the coronavirus (the SARS-Cov-2 spike proteins). This cellular generation of proteins then elicits an immune response in which the body produces virus-neutralizing antibodies even before infection with the real pathogen.

There is little question that the mRNA presents an attractive opportunity for creating a preventive vaccine. Relative to traditional approaches, mRNA therapeutics can offer a quick development-manufacturing-scaling-up cycle.

However, the mRNA delivery itself poses multiple challenges. Designing the right vehicle is crucial for proper tissue targeting, cellular uptake and ultimately the product’s pharmacokinetic and pharmacodynamic performance. Therefore, the mRNA component of a vaccine must be “packed” properly, typically into stable small lipid spheres, so-called lipid nanoparticles (LNPs).

Still, recent advances in LNP, decades of research, successful launches of other RNA therapies and, undoubtably, the COVID-19 urgency accelerated the recent developments of the mRNA platforms to the benefit of this modality.

This acceleration has had significant implications for the whole mRNA market. The requirements for light-speed research has connected global scientific hubs and increased the available knowledge in disease mechanisms and the development of potential mRNA-based therapies, which has led to fast-track mRNA drug authorizations. Meanwhile, fast scaling of the manufacturing process has fueled cooperation between biotechnology and pharmaceutical giants, as well as multiple contract development and manufacturing organizations (CDMOs) and technology providers. While uncommon handling requirements for mRNA therapies have created additional challenges in the supply chain, this has strengthened interactions among pharmaceutical companies, logistics service providers and governments.

Opportunities beyond COVID-19 vaccines for mRNA therapies

While mRNA technologies carry a broad theoretical and some empirical applicability in specific scenarios where an immune-related response is required, such as infectious disorders and cancer, they also could be designed to directly encode functional versions of missing or altered proteins, including immune-silent approaches.

There is a promising subset of early clinical mRNA assets. In addition to oncology therapies for solid tumors, which represent 60% of the pipeline, there are other infectious disease-modifying drugs, such as antivirals, as well as metabolic, cardiovascular and respiratory therapies.

There are great breakthroughs… and there are challenges

Although there has been a huge buzz around mRNA therapies recently, only few companies have been able to move their ideas forward, converting science into clinical practice. For example, COVID-19 vaccination trials were accelerated to get patients immunized as quickly as possible.

At the same time, it remains to be seen whether lessons learned from the COVID-19 vaccination program may translate, either directly or indirectly, into other therapy areas. For example, although there has been success igniting an immune reaction, it remains unclear whether this success can be replicated for other mechanisms of action, such as direct expression of metabolic enzymes, the production of hormones, or any other proteins.

Also, given the molecular variability and genetic instability, most cancer therapies might have to embark on a personalized approach, limiting large-scale production opportunities. Long-term effects on patients related to packing mRNA therapies into lipid spheres need to be further investigated.

What does the future hold for mRNA?

Although the COVID-19 vaccine landscape remains fluid, mRNA platforms will likely continue to solidify as a therapeutic concept and capture a tangible share of the preventive vaccines market. Beyond the near-term COVID-19 opportunity, the mRNA market is expected to grow significantly, reaching almost $5b by 2025.Riding current mRNA successes, numerous mRNA startups, spread mainly across the US and Europe, have secured approximately $4.6b in investment flows.2

There are several great ideas for the application of mRNA therapies beyond the use in preventive medicine (though infectious diseases remain the second-largest group by numbers of trials based on our pipeline scan, with approximately 30%). As the potential for using mRNA in eliciting an immune response has been also seen as an interesting option in the treatment of cancer, the largest number of current research projects is focused on that therapy area — often in trials on personalized therapies. But mRNA is also emerging in other disease areas and with other mechanisms of action, including the production of hormones or cytokines in areas such as metabolic diseases, cardiovascular diseases, or respiratory illnesses.

Figure 2: mRNA clinical pipeline assets
mRNA clinical pipeline assets

However, for mRNA therapies to become a common practice, they may need further medical understanding, experience, and scientific claims. Nevertheless, we believe the mRNA space is poised to benefit from ongoing innovation.3

Specifically, EY-Parthenon sees two potential paths for future success in the mRNA market:

  1. Mass ready-to-treat therapies: Other therapies have already launched successfully in common indications, such as diabetes and cardiovascular, with strong growth in volume demand. Given the nature of mRNA manufacturing, drug makers will not only need to scale-up their internal capabilities, but also cooperate with external manufacturers and other large pharmaceutical players. Updated infrastructure stemming from COVID-19 programs could support a future mRNA pipeline.
  2. Niche therapies: Here the focus would be on small-scale, high-personalized mRNA therapies, such as rare diseases or specific cancer indications. Under this scenario, pharmaceutical companies may have an option for innovative medicines.

First approved drugs set the scene for future mRNA therapies

As RNA therapeutics continue to come of age, they are receiving significant attention from investors, regulators and payers alike.The first approved mRNA drugs set the scene for upcoming therapies. Companies deciding to embark on this journey should track the competition, identify industry standards and potential differentiating points and start shaping their mRNA portfolio early.

Given the relative novelty of the mRNA technology, companies will want to build the case at the intersection of the three S’s: science, system and society. They will need to demonstrate their products hold their promises, show value for the society and project a positive social message.

EY teams believe there will be an abundance of opportunities for sustained benefits in a post-pandemic world. While it’s still too early to tell with certainty, mRNA technology appears well-positioned to become a new rising star of the pharmaceutical industry.

This article has been authored by Dr. Isabelle Heiber, Dr. Elias Eckert, Miroslav Iacovlev MD, and Joey Wilson, all of EY-Parthenon.

The views expressed by the authors are not necessarily those of EY-Parthenon or other members of the global EY organization.

  • Show article references#Hide article references

    1. Global mRNA vaccines & therapeutics sales market report 2020, 360 Research Reports, https://www.360researchreports.com/global-mrna-vaccines-therapeutics-sales-market-16690529, accessed February 2021.

    2. Top 18 mRNA startups, medicalstartups.org, https://www.medicalstartups.org/top/mrna/, accessed February 2021.

    3. EY-Parthenon analysis; Biomedtracker (Informa Business Intelligence, Inc.); U.S. National Library of Medicine, clinicaltrials.gov, February 2021.

    4. EY-Parthenon analysis, February 2021.


The COVID-19 pandemic has created a lot of headlines for mRNA therapies. With a host of uses beyond vaccines, and with investment pouring in, biotech and pharmaceutical companies are looking at mRNA technology to help treat everything from cancer to cardiovascular and respiratory disease — if they can make it scalable and it can provide value for money.

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