Title:Peptide Therapeutics and the Pharmaceutical Industry: Barriers Encountered Translating from the Laboratory to Patients
Volume: 23
Issue: 37
Author(s): John Rafferty, Hema Nagaraj, Alice P. McCloskey, Rawan Huwaitat, Simon Porter, Alyaa Albadr and Garry Laverty
Affiliation:
Keywords:
Anticancer, antimicrobial, biostability, formulation, manufacture, peptides, self-assembly, scaleup.
Abstract: Peptides are receiving increasing interest as clinical therapeutics. These highly
tunable molecules can be tailored to achieve desirable biocompatibility and biodegradability
with simultaneously selective and potent therapeutic effects. Despite challenges regarding
up-scaling and licensing of peptide products, their vast clinical potential is reflected in the 60
plus peptide-based therapeutics already on the market, and the further 500 derivatives currently
in developmental stages. Peptides are proving effective for a multitude of disease
states including: type 2 diabetes (controlled using the licensed glucagon-like peptide-1 receptor
liraglutide); irritable bowel syndrome managed with linaclotide (currently at approval
stages); acromegaly (treated with octapeptide somatostatin analogues lanreotide and octreotide);
selective or broad spectrum microbicidal agents such as the Gram-positive selective
PTP-7 and antifungal heliomicin; anticancer agents including goserelin used as either adjuvant
or monotherapy for prostate and breast cancer, and the first marketed peptide derived
vaccine against prostate cancer, sipuleucel-T. Research is also focusing on improving the
biostability of peptides. This is achieved through a number of mechanisms ranging from replacement
of naturally occurring L-amino acid enantiomers with D-amino acid forms, lipidation,
peptidomimetics, N-methylation, cyclization and exploitation of carrier systems. The
development of self-assembling peptides are paving the way for sustained release peptide
formulations and already two such licensed examples exist, lanreotide and octreotide. The
versatility and tunability of peptide-based products is resulting in increased translation of
peptide therapies, however significant challenges remain with regard to their wider implementation.
This review highlights some of the notable peptide therapeutics discovered to date
and the difficulties encountered by the pharmaceutical industry in translating these molecules
to the clinical setting for patient benefit, providing some possible solutions to the most challenging
barriers.
