Industry sources project a continuing 10 to 15% growth in the market for biotherapeutic peptide new chemical entities, and more modest growth of slightly greater than 10% for generic peptides. These projections, however, predate the current global economic downturn and ongoing financial instability, and there is growing concern that some projects presently in corporate pipelines might be stalled and new projects may be delayed, with a worried eye focusing primarily on the biotech sector and companies that rely on venture capital funding.
“There is reduced appetite for risk in the financial markets,” observes Johan Devenyns, Ph.D., head of Solvay Peptides, the parent company of Peptisyntha.
What had largely limited more widespread development of therapeutic peptides in the past has been the cost of manufacturing, according to Huw Nash, vp of corporate development and a cofounder of Aileron Therapeutics. Within the past five to ten years, though, “solid-phase synthesis of large helical peptides has become economically viable,” says Nash, citing the commercial success of Roche’s Fuzeon for HIV infection and Amylin’s Byetta for the treatment of type 2 diabetes.
Now, instead of worrying about manufacturing and cost issues, peptide drug developers are focused on expanding delivery strategies and improving the pharmacokinetic properties of therapeutic peptides.
The current absence of clear regulatory guidance from the FDA regarding impurity specifications for peptides in clinical trials presents challenges for manufacturers and their clients. “We continue to see drug product sponsors opting for the impurity guidelines for small molecules, even though complex peptides are specifically excluded from these,” says Rodney Lax, director of sales and marketing at PolyPeptide Laboratories (PPL). “Given the low toxicity for peptides in general, this approach places unreasonable technical and economic demands on the CMO, particularly for more complex peptides.”
“The therapeutic peptides market is still predominantly U.S.-oriented,” says Dr. Devenyns. More than two-thirds of demand comes from the U.S. market. The bulk of solid-phase synthesis capacity resides in the U.S., with solution-phase operations primarily located in Europe.
In describing the competitive landscape outside the U.S., Dr. Devenyns points to a trend in which peptide companies have gone through a round of consolidation and are currently looking to the east for increasing the scope of their manufacturing operations.
At Peptisyntha, the expansion under way at its Torrance, CA, site continues. The new QC/QA laboratories and offices, is scheduled to be ready by March. The company has also leased an additional building adjacent to its existing facility that will provide increased production capacity in 2010—predominantly for solid-phase peptide synthesis.
At the Brussels site, where the company’s solution-phase manufacturing capability is based, Peptisyntha took into operation new QC labs and a new synthesis pilot over the past 6-12 months. Additionally, new GMP warehouses went into use earlier this year in Brussels for receipt and storage of materials under controlled conditions. All of these expansions were built to comply with cGMP standards.
A key goal for 2009, according to Dr. Devenyns, is the installation and validation of a manufacturing execution system that will automate series of workflow processes involved in peptide production. This will include automated follow-up of the flow of materials moving in and out of the company’s new warehouses and will constitute the backbone of a productivity upgrade. Additionally, new pilot capacity for purification and lyophilization will also be brought on-stream. Peptisyntha was inspected in August 2008 by the Belgian Federal Agency for Medicines and Health Products, on behalf of EMEA, and a GMP certificate was granted.
With the acquisition of NeoMPS, previously the peptide manufacturing arm of Isochem, and its facilities in Strasbourg, France, and San Diego, PolyPeptide Laboratories has added substantial manufacturing capacity to its ongoing GMP operations in the U.S., Denmark, Sweden, and India. It also broadened its range of offerings, providing services to organizations seeking catalog peptides, radio-labeling services, small-scale non-GMP synthesis, as well as contract manufacture of amino acid derivatives and organics.
The acquisition of NeoMPS gave PPL a “broader window for pipeline projects,” says Lax, in particular enabling the company to pursue more small-scale GMP projects, such as vaccine production, for which initial GMP lots typically require only about 10 grams of peptide, as well as the general ability to compete for earlier-stage projects.
About 35% of PPL’s business is in generic peptides, which Lax describes as an established market that will likely remain fairly stable even in the current economic uncertainty. An additional 25% of the company’s revenue stream depends on contracts with large pharmaceutical companies, adding to Lax’s confidence that PPL is in a good position to weather the economic storm.
The company’s new facility in India will be operational later this year and will be dedicated initially to generic peptide production. Expansion of manufacturing capacity is also ongoing in Scandinavia and Torrance.