DDW’s Diana Spencer takes a closer look at three companies hoping to be the first to bring new mRNA therapeutics to the market.
Although the concept of using mRNA to make therapeutics or vaccines has been around for decades, it took the urgency of a global pandemic for it to become a reality. Now, there are many mRNA-based therapeutics in clinical development and mRNA cancer vaccines have been promised by 2030.
So which companies are taking the lead in this market?
Since the successful development of its mRNA-based Covid-19 vaccine mRNA-1273 (Spikevax) in 2021, Moderna has set out to be a leader in this sector and has the most and most advanced candidate therapies in development.
Most significant was the recent announcement of positive findings in the company’s Phase IIb KEYNOTE-942 clinical trial, which proved that the personalised cancer vaccine mRNA-4157/V940, created in collaboration with Merck, improved recurrence-free survival (RFS) in patients with high-risk melanoma.
mRNA-4157/V940 has received Priority Medicines (PRIME) scheme designation by the European Medicines Agency (EMA) and Breakthrough Therapy Designation by the US Food and Drug Administration (FDA) in this indication, so it is hoped that it will be the first mRNA cancer vaccine available on the market.
Moderna also has two other mRNA cancer vaccines in Phase I studies; mRNA-5671, which is being investigated in patients with KRAS mutant advanced or metastatic non-small cell lung cancer, colorectal cancer or pancreatic adenocarcinoma, and checkpoint vaccine mRNA-4359, which is being trialled in advanced solid tumours.
The company also has investigations ongoing into vaccines for Cytomegalovirus, Epstein-Barr virus, Zika and Nipah virus, and its mRNA-1345 vaccine for RSV could be close to regulatory approval, having recently met its primary endpoints in a Phase III trial in older adults.
In rare diseases, Moderna has several mRNA therapeutics in clinical development, including one in Phase II, a treatment for Propionic acidemia (PA), for which the company recently announced encouraging trial results.
Another major player in the mRNA field is German company BioNTech, which has vaccines for solid tumours melanoma, prostate cancer, head and neck cancer, breast cancer, lung cancer and colorectal cancer currently in Phase I or II trials.
Pfizer and BioNTech’s mRNA Covid-19 vaccine Comirnaty was the first to receive regulatory approval and reported the highest vaccine sales in 2021 at $41.3bn, much higher than Spikevax.
Continuing their collaboration in this field, Pfizer and BioNTech initiated a Phase I trial and received FDA Fast Track designation at the end of 2022 for their investigational combined vaccine for Covid-19 and influenza. In early 2023, the partners initiated a Phase I/II study of the first mRNA-based shingles vaccine, and are currently in Phase III trials for their Influenza vaccine BNT161.
A partnership between the UK government and BioNTech aims to accelerate clinical trials of personalised immunotherapies for cancer and infectious disease vaccines. Access to the trials will be through the Cancer Vaccine Launch Pad, which is being developed by NHS England and Genomics England.
Close behind these two heavyweights, American company Arcturus Therapeutics is also very active in the mRNA field, thanks to development of its STARR vaccine technology and LUNAR delivery platform.
Arcturus’ self-amplifying Covid-19 vaccine met its primary endpoint in Phase III trials in 2022. Following this, the company entered into a collaboration agreement with CSL to develop vaccines using this technology for Covid-19, influenza, pandemic preparedness, as well as three other globally prevalent respiratory infectious diseases.
Much like Moderna, Arcturus has recognised the potential for mRNA in the rare diseases market. ARCT-810, the company’s mRNA therapeutic candidate for ornithine transcarbamylase (OTC) deficiency, is currently enrolling patients for a Phase II study, and was granted US Food and Drug Administration (FDA) Fast Track Designation in June 2023.
In early 2023, the company received approval to take its cystic fibrosis candidate ARCT-032 to Phase I trials in humans and is currently involved in other partnered development programmes for diseases including glycogen storage disease type III, and hepatitis B virus.
Find out more about this fascinating technology and the future for mRNA in the DDW webinar ‘Where are the breakthroughs in mRNA drug discovery and development?’ on July 19.