Therapeutic peptides – What makes them different?
Currently peptide therapeutics have only a 2 to 5% market share of the totally sold drugs (1). The annual growth rates are continuously over average during the last years. New biological and chemical synthesis, purification and screening technologies might even enhance the discovery and clinical development of peptides in the future. In combination with rapidly advancing formulation and delivery technologies derived from protein therapeutics alternative applications routes than oral more peptide therapeutics are now passing and entering clinical phases. The higher target selectivity and lower toxicity und thus more favourable side specific pharmacokinetic properties are major reasons for the over 5-fold higher success rate of peptides to pass a phase 1 study compared to small molecules (2).
In this review peptides are considered to be polymers of amino acids with a maximal length of 50 amino acids. The size from 51 to 100 residues (about 6 to 12kDa) is nowadays covered by the increasing number of miniproteins or individual protein domains (3). Over 50 peptides are currently sold as drugs (2). The global market size of therapeutic peptides in 2017 was 22 billion USD and estimated to exceed 50 billion USD by 2024 (4).
After 6 peptide approvals during 2017 (5) only 1 peptide therapeutic out of 59 approvals by the FDA (6) was granted 2018. This is (Lutathera) a lutetium Lu 177 dotatate radioligand for the treatment of gastroenteropancreatic neuroendocrine tumors (7). A nearly exhaustive analysis of the clinical success rates during 2006 to 2015 (8) revealed positive approvals of the clinical phase 2 of 10% for new chemical entities (NCE), 41% for new biological entities (NBE) and 28% for peptides (non-NCE) (8). The ranking in the other clinical phase transitions was the same and the peptides equaled t ...