be reserved for polypeptides containing more than 100 consideration when designing new peptide therapeutic amino acids, but on the clear understanding that these candidates. too are essentially peptides. Apart from approved drug substances, CMOs Table 1 lists some of the currently approved peptide manufacture several other products according to cGMP. therapeutic drugs. The number popularly mentioned in There are at least 3 approved veterinary products the public domain is “more than 60”. At the latest count, (deslorelin, lecirelin and gonadorelin hydrochloride) we have been able to identify 72. This includes one as well as 8 in vivo diagnostics (ceruletide, corticorelin, medical device and 9 non-FDA, non-EMA approved. This cosyntropin, pentetreotide, pralmorelin, secretin, catalog is by no means complete – we have identifi ed sincalide and somatoliberin). several other tentative peptide drug products that have Peptide APIs in clinical trials also form a major source of marketing approval outside North America and Europe. income for the CMOs. According to Kaspar & Reichert (4) there were 40 peptides in PI clinical trials in 2013, 74 The average number of peptide therapeutic drug in PII and 14 in PII/III. Phase III trials were dominated by products being approved each year has risen from oncology + infectious disease, PI and PII encompassed about 2 in 2000 to about 2.5 in 2015 (Figure 1). The more diverse therapeutic areas, with substantial bias to relatively fl at profi le of the graphic belies the actual metabolic disease + oncology. The number of peptide market growth which is being driven by the dollar conjugates was also increasing; 20% of peptides volumes of the individual products and not the number currently in PI were conjugates. of new approvals. One factor that should stimulate business for the peptide CMO industry in the Table 1. Examples of currently approved peptide therapeutic next decade is the steady shift drugs. towards biologics. In 2015, 29% of all approved drugs in the USA were biologics, and world-wide in 2020 an estimated 55% of the 40 top-selling drugs world-wide will be biologics. In the next 5 – 10 years, expect to see a merging and/or meshing of recombinant, chemical, and enzymatic manufacturing technologies that will pave the way for commercial manufacture of new classes of biologics that will require chemically synthesized peptide fragments. These would include 1Market approval in Russia; 2market approval in China; 3recombinant product new antibody-peptide drug > 50 amino acids; 4market approval in Bornia & Herzegovina; 5medical device; conjugates, fusion proteins with 6market approval in Australia; 7syn:cosyntropin, also approved diagnostic. non-proteogenic amino acid residues and post-translational modifi ed proteins.

At least 75% of all peptide drug products are injected. The increasing number of alternative delivery routes and advanced formulations (10,11) should lead to greater patient acceptance of peptides and biologics. While most of the new delivery technologies are currently targeted at extending life- cycles of existing drugs, this will hopefully change and the route of Figure 1. New peptide therapeutic drug products approval administration will be taken into 2000-2015.

PHARMA HORIZON 67 Special issue