News & Press
Chemistry Today Oligo Peptide Supplement, April 2018
Advances in drug delivery, new technology, and a deeper understanding of oligonucleotides have led to escalating interest in developing these promising compounds. Research on these chemically synthesized compounds began about 50 years ago to address a wide range of conditions considered “undruggable” with small-molecule therapeutics. While development, delivery and regulatory challenges along with trial failures discouraged many developers, there has been a renewal of interest in oligonucleotides since early 2014, according to the numbers of NCEs entering clinical Phase I.
Today, about 170 clinical trials (1) involving oligonucleotide compounds are registered, representing a decrease since 2015 (Figure 1). Just as the number of new chemical entities has been decreasing, so has the number of oligonucleotides entering clinical phase I since 2016 (Figure 2). Ironically, the hope for these molecules has been realized, as several oligos (30 APIs) successfully passed phase II, and five [fomivirsen (Vitravene),1998; pegaptanib (Macugen), 2004; mipomersen (Kynamro), 2013; eteplirsen (Exondys 51), 2016; nusinersen (Spinraza), 2016] have been FDA approved.
The decline in trials is largely due to a lag from early discovery until these therapies enter human studies. Also, delivery remains an important hurdle, since oligos are large and do not enter cells by diffusion. However, several compounds already yield significant treatment effects.