#27 Deeptech Insights - The Potential of RNA Therapies: Exploring the Future of Innovative Treatments
DeepTech Innovations Unlocked: This Week Our Expert News Analysis for Smarter Business and Investment Decisions
By Sarah Brunet Amouyal, Deeptech Expert
What is going on?
RNA therapy belongs to cell and gene therapies. It refers to a class of therapeutic iapproaches that utilize RNA (RiboNucleic Acid) molecules to prevent or treat various diseases.
The recent advent of a series of effective messenger RNA-based vaccines in response to the COVID-19 pandemic has reignited research interest in RNA Therapy. The aim of this therapy is to target diseases that cannot be treated by other conventional drug groups. Currently, a large panel of clinical studies are underway for a variety of RNA-base therapeutics against incurable diseases, or to bring some therapeutic alternative for current diseases.
What does it mean?
RNA, a new therapy ?
Yes and no. Messenger RNA (mRNA) was discovered back in 1962. It involves the use of synthetic or modified RNA molecules to target specific genes or gene products in order to modulate their expression and activity. But it’s in the last decade that research and development in RNA therapy have gained significant momentum. The emergence of Covid-19 vaccines has further spotlighted the potential of 1RNA therapy, paving the way for a future with extensive disease prevention and treatment options.
What are the different types and theirs therapeutic potentials ?
RNA therapy encompasses various types each with its own therapeutic potential:
(1) RNA interference (RNAi) utilizes small molecules like siRNA and miRNA to bind to complementary mRNA, preventing protein translation and offering treatment possibilities for genetic disorders, viral infections, and cancers.
(2) Antisense oligonucleotides (ASOs), short sequences of RNA or DNA, that modulate gene expression by binding to target mRNA, showing promise in treating genetic disorders such as spinal muscular atrophy and Duchenne muscular dystrophy.
(3) Messenger RNA-based vaccines, like those developed for Covid-19, provide instructions to cells to produce specific antigens, stimulating immune responses and building immunity against targeted viruses or cancer tumors.
(4) Additionally, RNA-based gene therapy introduces therapeutic genes into cells or modifies the expression of existing genes, offering potential solutions for genetic disorders through gene replacement or defective gene repair.
Revolutionising therapies ?
RNA therapeutics offer significant advantages:
They are highly target-specific, allowing for specific modulation of gene expression which enables easy switching and customization for different therapeutic purposes. Predictability in terms of pharmacokinetics and pharmacodynamics facilitates better understanding and control of their effects. Furthermore, RNA therapeutics are economical compared to antibodies or protein drugs. And most importantly, they are relatively safe, as most do not alter the genome.
However, there are challenges to overcome. Efficacy and safety testing is necessary, and delivering RNA into cells can be challenging due to its easily degradation. Successful delivery requires penetration of the cell membrane and escape from endosomal entrapment. Additionally, despite their specific targets, therapeutic RNAs may have off-target effects, which can limit their utility as drugs.
Why should I care?
💸For markets: an exponential sales growth is estimated to happen in the near future.
Based on cellandgene market report, Cell and gene therapies (CGT), including RNA therapies, are considered to be a transformative force in the pharmaceutical industry, driving significant sales growth. Even though CGT accounted for just over 1% of global drug sales in 2022, it is expected to reach a growing Compound Annual Growth Rate (CAGR) of 46% from 2022 to 2028, resulting in an estimated $86 billion in sales. Compared to conventional drugs and non-CGT biologics which are expected to achieve only a CAGR of 5% during the same period, the immense potential of CGT to shape the next generation of drugs and become a major revenue driver for pharmaceutical companies is just about to explode.
In the RNA therapy market, start-ups often take the lead, forming partnerships with big pharmaceutical companies to facilitate market entry during the final stages of development. Here are the top pharmaceutical companies ranked by the number of RNA therapeutics and vaccine agents in their R&D pipelines, showcasing their commitment to advancing RNA-based treatments and prevention methods. These collaborations only reflect the growing significance of RNA therapies and their potential impact on healthcare:
1. Moderna, mRNA, 47 RNA therapeutic, and vaccines agents in the development pipeline.
2. Ionis Pharmaceuticals, ASO, 43
3. BioNTech, mRNA, 21
4. Alnylam Pharmaceuticals, SiRNA, 19
5. Sirnaomics, SiRNA, 19
6. Dicerna, SiRNA, 14
7. NOXXON Pharma, Aptamer, 14
8. Arrowhead Pharmaceuticals, SiRNA, 13
9. CureVac, MRNA, 13
10. Sarepta Therapeutics, ASO, 11
11. Stemirna Therapeutics, mRNA, 11
12. Astrazeneca, mRNA,SiRNA, ASO, miRNA, 10
13. Beam, CRISPR, 10
14. Cartesian Therapeutics, mRNA, 9
15. Silence Therapeutics, siRNA, 9
🧑🏿🤝🧑🏻For society: RNA therapies are revolutionising the therapeutic landscape.
RNA therapies have transformed significantly the therapeutic landscape by bringing innovative solutions to patients. Some RNA therapies have already made their way to the market showcasing their effectiveness:
Leqvio®, a siRNA therapy developed by Alnylam/Novartis received FDA approval in 2021 to treat familial hypercholesterolemia, a cardiovascular disease.
Waylivra®, an ASO therapy created by Ionis Pharmaceuticals, gained approval in the EU in 2019 for familial chylomicronemia syndrome, a metabolic disorder.
Oxlumo®, an siRNA therapy developed by Alnylam, obtained FDA approval in 2020 for kidney diseases.
Numerous ASO treatments for Duchenne disease received FDA approval between 2016 and 2020.
Notably, the mRNA-based Covid-19 vaccines developed by Pfizer-Moderna were approved by the FDA in December 2021.
The pipeline for RNA therapy is highly promising with significant research and development efforts underway. There has been a relevant increase in publications related to all types of RNA therapies over the past decade, indicating the active R&D landscape. Clinical studies are being conducted across various therapeutic areas.
Cancer research has attracted the highest number of therapeutics and vaccines in the research phase, followed by infectious diseases due to the discoveries made in Covid-19 vaccine development. Approved treatments are most prevalent in neurological and neuromuscular diseases, followed by cardiovascular and infectious diseases. The potential for RNA therapy development holds great hope for advancing patient care and addressing a wide range of medical conditions.
🔮What’s next?
RNA therapy2 has gained significant attention in recent years thanks to the active investments and developments in R&D to treat various diseases. It could offer new hope for patients to have innovative treatment and to fill a gap in certain therapeutic areas.
However, there are many challenges to overcome:
Carry of RNA molecules : researchers have been working on developing
various delivery systems to improve the stability, targeting and effective delivery of RNA molecules.
Clinical trials : play a crucial role in the development of new molecules but not all candidates will ultimately reach the market carrying a degree of risk in the pharmaceutical industry. Despite progressing through the rigorous testing phases, including Phase 3 trials, some molecule developments may unexpectedly stopped at the final stage.
Regulatory approval : numerous clinical trials are needed to evaluate safety
and efficacy of RNA therapies in order to compile the data and obtain the regulatory approval (FDA, EU etc) making the process longer than expected.
Startups Support : the majority of RNA Therapy is being developed by small
companies whose success relies on the launch of these therapies. Their success depends on external investors and the support of larger pharmaceutical partnerships. Such support enables them to navigate the complexities of clinical trials, regulatory approvals, and market entry, ensuring that innovative RNA therapies can reach patients in need.
In my next article I will delve into the exciting innovations in the fight against Covid-19 infection and explore the groundbreaking developments in mRNA vacciones, cutting-edge treatments and the latest guidelines to combat the virus.
Subscribe & Stay tuned to learn the advancements on the horizon!
Check this publication published in Experimental & Molecular Medicine in 2022 from Young-Kook Kim to learn more about the history of RNA therapies.
Check this publication published in Sciences China Life Sciences in January 2023 from Zhang, C.& al. on the pipeline of RNA therapies.