Advances in synthetic chemistry, solid support materials, purification technology, and biological drug delivery strategies have all contributed to strong growth and expanding interest in peptide drugs, especially among large pharma companies. Even with the global economic downturn, the market for GMP peptides continues to grow—albeit at a reduced rate—with the progression of established therapeutic peptide projects through clinical development and the emergence of new peptide drug candidates from discovery research.
In the research sector, demand for peptides also continues to rise at a somewhat slower pace, particularly for peptide libraries used in drug screening, target validation, epitope mapping, and structure-activity studies.
Research-grade peptide producers in the West are facing strong competition from emerging suppliers in the Far East, where lower operating costs are driving down the cost of peptides. Manufacturers in India and China in particular are well positioned to supply the rapidly growing Asian market for research peptides, and some Western producers are gearing up to compete for this growing market base by opening satellite facilities in the Far East.
Companies such as American Peptide Company aim to compete with these lower price points by emphasizing quality and service, and specializing in difficult syntheses such as producing hydrophobic or hydrophilic peptides and modified peptides that offer enhanced stability, solubility, or other desirable characteristics.
In April, American Peptide completed the first phase of its expansion project, with construction of five new class 100,000 purification suites, doubling the existing purification capacity. This increased capacity is attributable to the addition of purification columns up to 12 inches diameter for large-scale projects. The expansion also included three new class 10,000 packaging suites. The next phase of the expansion will add large-scale synthesis suites and lyophilization capacity for producing multikilogram peptide APIs per batch.
The annual growth rate for the therapeutic peptide market is estimated at about 7.5%—down from the double-digit growth the industry enjoyed in recent years. Predictions place the value of the GMP peptides market at more than $13.4 billion by 2010. Some estimates project only 0–5% growth in 2009, with the market beginning to show improvement toward the end of the year.
Therapeutic peptides continue to increase in length and complexity, with 30, 40, and even 50+ amino acid peptides moving into clinical pipelines. Improvements in synthesis and purification technology are allowing for the efficient and cost-effective production of these longer peptides. The development of higher-quality resins for solid-phase synthesis and price reductions for some reagents commonly used in peptide synthesis have also contributed to the lower cost of synthesizing longer peptides.
With 14,500 square feet of new manufacturing capacity now in operation, Bachem’s six production sites in the U.S. and Europe are poised to handle the continuing growth of the peptides market, says Philip Ottiger, president and CEO. While “we are seeing a concentration of projects” by biotech companies, which are focusing their efforts on a few select projects and delaying others until the market heats up, the pharmaceutical industry “is starting to like peptides again,” observes Ottiger. “We are seeing enormous interest from pharma.”
This interest extends beyond peptide drugs to the use of GMP peptides as drug carriers. Ottiger describes a growing interest in cytoconjugation, in which peptides conjugated to cytotoxic drugs such as the chemotherapeutic agent doxorubicin can improve drug selectivity, enhance cell penetration, and reduce drug toxicity. Synthesis of the relatively short peptides used in cytoconjugation—typically 8 to 20 mers—is straightforward, but formation of the cytoconjugate is a complicated process.
Bachem built a facility devoted to cytoconjugation products about two years ago, and Ottiger reports growing demand, with an expanding focus on conjugation to PEGylated peptides or albumin and interest in cytoconjugation to the intestinal peptide glycogen-like peptide-1 for the development of therapeutic compounds targeting diabetes mellitus.
Contributing to the renewed interest in peptide drugs are improvements in pharmaceutical formulation technology, notes Ottiger, which are enabling better stabilization of peptides and more cost-effective methods for large-scale production that can be used in place of lyophilization, such as spray-drying technology and precipitation.
Mimotopes continues to benefit from its alliance with Genzyme Pharmaceuticals, aimed at providing seamless peptide synthesis, scale-up, and GMP manufacturing from discovery and development through to clinical testing. Nicholas Ede, Ph.D., CEO of Mimotopes, points to the use of pseudoproline dipeptides as a competitive advantage.
Pseudoproline technology prevents secondary structure formation during peptide synthesis, enhancing coupling efficiency and chain elongation, and resulting in higher purity of crude peptides and better overall synthesis yields. Mimotopes uses pseudoproline reagents in the synthesis of its research-grade peptides, and Genzyme further developed the technology and demonstrated the advantages of these reagents in large-scale GMP synthesis. Genzyme also offers these reagents in bulk—in quantities from 100 g to hundreds of kilograms—for large-scale production; these include high-purity Fmoc- or Z-protected pseudoproline dipeptides.
In response to rising competition from India and China, Mimotopes established a relationship with the Chinese company Venturepharm Laboratories, which provided a facility that now houses Mimotopes China. The new facility employs Mimotopes’ peptide-synthesis technologies, follows the company’s standard operating procedures, and its staff is trained by Mimotopes employees. It can not only take advantage of the lower cost base of employment in China, but it has also tapped “the incredible local talent pool of peptide chemists,” says Dr. Ede.
Mimotopes recently launched, in collaboration with GlaxoSmithKline and the University of Leeds (U.K.), REPLI, a fluorescence resonance energy transfer (FRET) rapid endopeptidase profiling library for use in identifying protease substrates. PepSet peptide libraries consist of fluorescently labeled tripeptide analogs that span the sequence surrounding the cleavage site of the substrate.