Increasing oligonucleotide production capacity to support the future
After decades of research, the oligonucleotide field has reached a tipping point and is generating huge interest and momentum. Fuelling this field is the pursuit of new technologies, from gene therapies to the surge in oligonucleotide affinity ligands, such as aptamers. Key players across the industry are rapidly expanding oligonucleotide production capacity and developing new, more efficient processes to support this rise in demand.
The rise of oligonucleotides
Oligonucleotides are being employed across the life sciences to enable new strategies, develop new therapeutics and pursue new targets that are not possible with traditional protein-based affinity ligands, such as antibodies and antibody alternatives.
Since 2018, the industry has seen the approval of nine new oligonucleotide therapeutic modalities, bringing the total approved oligonucleotide therapeutics to 13. The COVID-19 pandemic in 2020 spurred the rapid development and approval of two mRNA vaccines, which are among the most important and profitable vaccines in history. Equally, aptamer-based technologies, such as Optimers, are increasingly being used to identify new biomarkers and open up new therapeutic and diagnostic avenues and applications.
A step-change in oligonucleotide production
As scientists have embraced the power of oligonucleotide molecules the pipeline for oligonucleotide products continues to expand meaning that oligonucleotide manufacturers across the globe are racing to keep pace with the industry. Improvements are being made to oligonucleotide manufacturing processes to support an increase in the global production capacity and improve production efficiencies.
Aptamer Group recently conducted a survey of the current manufacturers offering large-scale oligonucleotide production; all of the manufacturers questioned stated their intention to expand existing oligonucleotide production facilities. Similarly, new manufacturers have observed the growth in the oligonucleotide field and are now developing production services and facilities within this area. Such expansions reflect the rise in demand for commercial-scale manufacture of oligonucleotides and the reduction in perceived risk associated with the development of oligonucleotide-based products. The increase in capacity resulting from expansion of current suppliers and the entrance of new players in oligonucleotide production into the market are expected to increase capacity and competition across the industry.
At the start of 2021, a UK-based collaboration between key industrial partners (Medicines Manufacturing Innovation Centre, AstraZeneca, Exactmer, Novartis and UK Research & Innovation), was launched to develop scalable, sustainable, and more cost-effective oligonucleotide production processes.
Breakthrough medicines building new production processes
This collaborative project was developed in response to the launch of the new ground-breaking cholesterol-lowering siRNA treatment, inclisiran. Intended for use by people with primary hypercholesterolaemia or mixed dyslipidaemia who have already had a cardiovascular event such as a heart attack or stroke, inclisiran can be given in primary care settings as a twice-yearly injection to people with high levels of LDL-cholesterol to reduce the chances of a second event. Cardiovascular disease is a leading cause of death across the developed world, thus the potential patient population requiring inclisiran therapy could be vast.
To enable sufficient production of this oligonucleotide therapeutic to serve the global market and remain economically competitive and improve cost efficiencies on any future oligonucleotide products, the collaboration with the Medicines Manufacturing Innovation Centre will deliver methods to enhance the production capacity and viability of large-scale oligonucleotide production.
Expected to be complete within three years, critical elements that will be addressed include improvements to the yield and efficiency of the oligonucleotide production process and reductions in the consumption of critical raw materials in the oligonucleotide production process, such as acetonitrile, to remove global supply challenges in the feasibility of large-scale manufacturing of oligonucleotides. Upon success this collaboration will transform the oligonucleotide supply chain, increasing capacity, reducing cost and improving oligonucleotide production processes for all forthcoming oligonucleotide products in the pipeline.
To understand more about oligonucleotide development and manufacturing and how this compares to standard antibody products, download our whitepaper below.