Therapeutics
ORAL PEPTIDE
THERAPEUTICS a holy grail or quixotic quest?
Technologies have been honed to overcome many of the challenges of administering peptide therapeutics orally, but obstacles remain before drug developers can fully realise the vast potential.
P
roteins and peptides are the building blocks of life and have evolved to become a very promising basis for targeting a range of dis- eases. Over the past 30 years, and especially the last 10 years, there has been a rapid growth in the development of therapeutic proteins, with a dra- matic increase in the number of protein-based drugs on the market.
The cornerstone of protein therapeutics was laid with the regulatory approval of insulin by the US Food and Drug Administration in 1982. As the first commercially-available recombinant protein, insulin soon became the gold-standard therapy for patients suffering from diabetes. Three decades have passed since insulin’s market introduction, and its success has inspired the development of myriad new thera- peutic proteins for a wide range of ailments. The advent of peptide-based therapeutics can be traced to the success of the initial protein biologics, with protein and peptides now being utilised across numerous indications, including cancer, autoim- mune, neurological and endocrine disorders. Currently, there are more than 200 approved ther- apeutic proteins and more than 100 peptides on the market, accounting for approximately 10% of the pharmaceutical market at a value of $40 billion per year. With hundreds of protein and peptide drugs in clinical trials and many more in preclinical development, this market is expected to continue to grow substantially over the next 5-10 years. A significant percentage of this growth is expected to come from peptide-based drugs.
Drug Discovery World Fall 2017
Peptides occupy a therapeutic niche between small molecules and large biologics, and are gener- ally classified as being a chain of amino acids con- taining 40 amino acids or less. Currently, the dis- ease areas driving the therapeutic use of peptide drugs are oncology, driven by a rising mortality and need for chemotherapy replacement, and metabolic diseases. The treatment of metabolic dis- eases via peptide therapeutics has largely centred around the epidemic growth in type 2 diabetes. Examples of such peptide drugs on the market today include Byetta, Victoza and Trulicity, which are part of the family of glucagon-like peptide-1 (GLP-1) receptor activators. These peptide drugs work by interacting with a receptor on the surface of pancreatic beta cells to stimulate the release of insulin for diabetes. In addition to metabolic dis- ease and oncology, the movement of the pharma- ceutical industry into rare diseases and orphan drugs has also been extended to peptides, and pep- tides are being further targeted at infectious dis- eases and inflammation.
Research has demonstrated that peptide thera- peutics can offer several advantages that are dis- tinct and desirable. Peptides serve a highly specific set of functions in the body that cannot be mim- icked by simple chemical compounds. Thus, com- pared with small-molecule active pharmaceutical ingredients, peptides are able to exhibit increased potency and selectivity due to specific interactions with their targets. As a result, peptides have the potential for decreased off-target side-effects and
59 By Dr Paul Shields
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