October 15, 2007 (Vol. 27, No. 18)

Stability, Cost, Delivery, and Manufacturing Challenges Are Being Worked Out

An analysis of launched peptide drugs and compounds in late-stage development indicated that the peptide market would grow in 2006 at a rate of approximately 5%. Beginning in late 2007, Phase III and some fast-track Phase II candidates will start moving through the registration and approval process. As these drugs get sanctioned and are marketed, the overall peptide market is expected to increase at around 10%. Further growth is expected toward the end of this decade and beyond.

The 67 marketed peptide drugs, tracked by the Pharmaprojects database, target 29 disease indications. Diabetes and osteoporosis ranked first and second in terms of number of medications. The majority of all these therapies have been on the market eight-plus years.

Looking forward, the market for peptide drugs will begin to show increased growth as drug candidates in Phase III and Phase II trials gain approval and enter the market. The peptide drug pipeline is robust, with the number of disease indications being investigated growing from 29 to 64. Disease areas with significant peptide therapeutic development activity include cancer, infection, and pain—all billion-dollar markets.

Peptides have potential as therapeutic molecules because they can be designed to engage a larger portion of the target protein thus providing greater specificity. The common goal of all drugs, whether small molecules, peptides, or antibodies, is highly specific binding to a target protein that plays a key role in the initiation and progression of the disease. A target protein can be present outside, in the membrane, or within the cell. Development of a compound to target a specific protein site can require extensive knowledge of the target, especially its amino acid sequence and folded structure.

Although the small molecule and peptide drug development processes are similar, the latter offers a number of drug development challenges. These obstacles include:

• less stability in bodily fluids

• more expensive manufacturing

• tough delivery due to rapid in vivo degradation by proteases

• production in larger quantities for clinical investigations, because of continuous administration due to rapid degradation

Peptide drugs currently represent a small but growing number of pharmaceutical molecules. Interest in these therapeutics has recently intensified with key developments in modifications of peptides with non-natural amino acids to increase stability, improvements in manufacturing to increase yield and reduce cost, synthesis of diverse peptide libraries to screen large sets of drug targets, and phage-display technology to identify target-specific peptides.

In the last two decades peptide drugs were usually close to 10 amino acids in length. Current peptides are much larger and more complex in structure, often incorporating modified or unnatural amino acids.

For example, the approved peptide drug Fuzeon contains 14 different amino acids in its 36-amino acid chain and requires 106 manufacturing steps. This complex process is used to produce 3,700 kg per year of Fuzeon, 60–300 times the annual production of synthetic peptides such as calcitonin or leuprolide.

This large production quantity is necessitated by the need to administer high-concentration doses of Fuzeon to achieve biological activity. For adults, this dosage translates into twice-daily subcutaneous injections of 90 mg each. Fuzeon manufacture requires approximately 44 different raw materials from 10 different countries and the process from start to finished product takes more than six months to complete. Fuzeon is synthesized in three fragments using solid-phase chemistry followed by a solution-phase step to combine the three fragments.

Peptides are currently being developed as vaccines and for therapeutic applications in a variety of diseases. These indications include allergy/asthma, arthritis, cancer, diabetes, growth impairment, inflammation, baldness, analgesia, ophthalmology, epilepsy, gynecology, obesity, and hemostasis as well as cardiovascular, CNS, antiviral, antibacterial, and GI diseases.

Anil Sehgal, Ph.D., is an independent consultant for biopharma companies. D&MD’s Peptides 2006: New Applications in Discovery, Manufacturing and Therapeutics market report covers emerging market trends, advances in peptide technologies, targets for peptide therapeutics, individual product examples, improved delivery mechanisms, and profiles of companies developing peptide drugs. To purchase or to receive sample content from this report contact [email protected] or visit www.drugandmarket.com/9214.

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