A quarter of a century ago, designer peptide drugs finally broke through the glass
ceiling. Despite the resistance by big pharma, biotechnology companies managed to
develop injectable peptide-based drugs, first against orphan or other small volume
diseases, and later for conditions affecting large patient populations such as type
2 diabetes. Even their lack of gastrointestinal absorption could be utilized to enable
successful oral dosing against chronic constipation. The preference of peptide therapeutics
over small molecule competitors against identical medical conditions can be achieved
by careful target selection, intrachain and terminal amino acid modifications, appropriate
conjugation to stability enhancers and chemical space expansion, innovative delivery
and administration techniques and patient-focused marketing strategies. Unfortunately,
however, pharmacoeconomical considerations, including the strength of big pharma to
develop competing small molecule drugs, have somewhat limited the success of otherwise
smart peptide-based therapeutics. Yet, with increasing improvement in peptide drug
modification and formulation, these are continuing to gain significant, and growing,
acceptance as desirable alternatives to small molecule compounds.
