Are we there yet?
An update on oligonucleotide drug development
Oligonucleotide therapeutics are a new class of drugs with only three commercialized drugs to date. In spite of this limited commercial success, the oligonucleotide field continues to grow rapidly. Many drugs have advanced to late clinical phases. A variety of drug delivery strategies have proven effective, and improvements continue to be made in the manufacturing technologies used to produce oligonucleotides. Growth in the oligonucleotide field is fueled by the renewed interest of large pharmaceutical companies and the emergence of startup companies with new intellectual property. The oligonucleotide field appears to be poised for success.
Oligonucleotide therapeutics have tantalized drug developers with the promise of rational drug design, lower drug development costs, and the ability to reach targets that conventional small molecule drugs cannot. Three oligonucleotide drugs have been approved by regulators, but oligonucleotides have not yet fully delivered upon their elusive promise. Large pharmaceutical companies have entered, exited, and then re-entered the oligonucleotide field in dramatic fashion. In 2012, Dr. Art Krieg, co-founder of Coley Pharmaceutical Group and now CEO of Checkmate Pharmaceuticals, summarized the evolving perspective of pharmaceutical companies towards oligonucleotides. Dr. Krieg stated that the first phase is an irrational exuberance that is followed by excessive skepticism when problems arise. Excessive skepticism is then followed by resurging enthusiasm and reinvestment as products are developed (1). Unfortunately, the period of excessive skepticism towards oligonucleotides also coincided with the economic turmoil of the Great Recession resulting in several very bleak years for the field. Venture capital was difficult to obtain, and frequently small biote ...