In August 2018, the FDA & European Commission announced the approval of Alnylam Pharmaceutical’s ONPATTRO, a first-of-its-kind RNA interference (RNAi) therapeutic. Evolution Executive’s latest timeline visualisation outlines the key events in the development and commercialisation of RNAi therapeutics, from Andrew Fire & Craig Mello’s initial discovery in 1998 through to Arrowhead and Johnson & Johnson’s $3.7B deal in October 2018.
What is RNAi?
RNA interference (RNAi) can be defined as a biological process in which double-stranded RNA molecules prevent the expression of disease-causing genes by enabling the destruction of their messenger RNAs (mRNAs), a consequence of which is the loss of protein expression. The concept offers an elegant mechanism of action to treat rare diseases, chronic liver diseases, cancer, cardiovascular disease and viral infectious diseases.
A Rocky Road to First Approval
The road to the first ever approval, Alnylam‘s ONPATTRO for the treatment of polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults, has been a rocky one. This is due to a combination of foreseen and unforeseen development challenges largely centred around targeting, off-target effects, toxicology, delivery and formulation. Additional commercial challenges have arisen with litigation being a significant complicating factor along with the loss of big pharma interest at key stages.
The following timeline provides an overview of the last 30 years of RNAi research, development and commercialisation, including Alnylam and other key developers: