What’s Next in Oligo Manufacturing: A Future Shift In Scale For Therapeutic Oligos

Written by Kimo Sanderson

From the “first wave” highs of the early 2000’s, to the clinical failure lows of the late 2000’s, and onward to the “second wave” surge of the 2010’s, the oligonucleotide therapeutics industry continues its upward trajectory in a more robust manner than ever.

This trajectory has been led by the flurry of FDA approvals in recent years, expanding from a mere handful of commercial products to more than fifteen today. What’s to come is even more interesting, as over 75% of oligos in the late phase trials and awaiting approvals are targeting broader disease areas, rather than the ultra-rare genetic disorders that have historically been targeted in the second wave. Therefore, patient demand for upcoming oligos is projected to be ten- to one-hundred-fold higher than the oligos for current rare disease indications. This increase is already foreshadowed by Novartis’ inclisiran (Leqvio^®), an siRNA drug to lower cholesterol which is now produced in the hundreds of kilograms two years since its launch, compared to less than ten kilograms required for Alnylam’s patisiran (ONPATTRO^®) an siRNA drug to treat hereditary amyloidosis.

Over 75% of oligos in the late phase trials and awaiting approvals are targeting broader disease areas rather than ultra-rare genetic disorders…patient demand is projected to be 10- to 100-fold higher…

The oncoming scale shift will fundamentally change the oligonucleotide manufacturing landscape 5-10 years from now. In this series of articles, we will explore implications of the scale shift towards future oligo manufacturing trends, not to be ignored by oligo equipment and consumable vendors, CDMOs and CROs presently serving this growing and exciting market segment.

For our first exploration, read “From Lyophilization Bottleneck to Liquid API.”