As a drug type, peptides offer certain benefits, such as specificity and potency, but they also present challenges, such as
poor stability and short halflife. Recent partnerships among large pharmaceutical companies and specialised companies, as
well as advances from academia, are seeking to resolve these problems.
Patricia Van Arnum
Peptides as drugs
Peptides and proteins have the size and functionality to effectively modulate intracellular protein–protein interactions,
but they often do not permeate cells and, therefore, are used to modulate extracellular targets such as receptors (1, 2).
According to a recent analysis of the peptide drug pipeline by the Peptide Therapeutics Foundation (3), the majority of peptide
candidates target extracellular molecules with less than 10% binding to intracellular targets. The most common extracellular
targets were G-protein coupled receptors (GPCR), which include nearly 1000 transmembrane proteins that activate cellular response.
During 2000–2008, 60% of peptides entering clinical development targeted GPCRs and most had agonist activity (3).
Although making up only a small portion of total drug candidates, the number of peptide drugs entering clinical development
has increased during the past several decades. The Peptide Therapeutics Foundation analysis, which excluded insulins, found
that the average number of new peptide candidates entering clinical development in the 1970s was 1.2 per year, rising to 4.6
per year in the 1980s, 9.7 per year in the 1990s and 16.8 per year through 2000–2008 (3). During 2000–2008, peptides entering
clinical study were most frequently treatments for cancer and metabolic disorders (including diabetes and obesity), respectively,
representing 18% and 17% of peptide drug development. Decreases were observed for peptides studied as therapies for treating
allergies, immunological disorders and cardiovascular diseases.
On a commercial level, several peptide-based therapeutics have reached blockbuster status, defined as having sales of $1 billion
or more, or near blockbuster status (3). These drugs, using 2011 global sales figures from company annual financial reports,
- Teva Pharmaceutical's Copaxone (glatiramer acetate), an L-glutamic acid polymer with L-alanine, L-lysine and L-tyrosine; (2011
global sales of $3.6 billion).
- Abbott's Lupron (leuprolide acetate), a synthetic nonapeptide analogue of the naturally occurring gonadotropin-releasing hormone
(GnRH or luteinising hormone-releasing hormone [LHRH]); (2011 global sales of $810 million).
- AstraZeneca's Zoladex (goserelin acetate), a decadpeptide and GnRH agonist and synthetic analogue of a naturally occurring
LHRH); (2011 global sales of $1.1 billion),
- Novartis' Sandostatin (octreotide acetate), a cyclic octapeptide with pharmacologic actions mimicking those of the natural
hormone somatostatin; (2011 global sales of $1.4 billion).
- Eli Lilly/Amylin Pharmaceuticals' Byetta (exenatide), a 39-amino acid peptide amide; (2011 global sales, Eli Lilly, $423 million,
Amylin, $518 million).
- Forteo (teriparatide recombinant), which contains recombinant human parathyroid hormone (1-34), is also called rhPTH (1-34).
It has an identical sequence to the 34 N-terminal amino acid (the biologically active region) of the 84-amino acid human parathyroid hormone; (2011 global sales of
$951 million) (4–9).