Although peptide drugs have been on the market for decades - insulin being the most prominent example - it was not until 10 to 15 years ago that the pharmaceutical industry really started to work seriously on the development of a new generation of peptide-based therapeutics, prompted by advances in the understanding of the genetics of disease. But initial enthusiasm was soon dampened by the realisation that drug delivery technologies at that time were not up to the task of getting these relatively large compounds into the body effectively, while production could be complex and expensive.
Now, with drug delivery seeing enormous strides forward, the stage seems to be set for a renaissance in peptide drugs.
A just-published report by Frost & Sullivan notes that the global therapeutic peptides market is currently valued at around $1 billion (€756m), with Europe contributing about $300m of that total, and will at around 10.5 per cent a year between 2003 and 2010. This means that the European market for peptides will double in size by 2010 to $605m.
"The rising need for new therapeutic approaches combined with the potential of peptides as active pharmaceutical ingredients (APIs) for effective drug formulation is contributing to rapid market development," says the report. But it cautions that manufacturers will need to show they can scale-up their production process to meet demand.
One driver behind the resurgent interest in peptides has been the development of large synthetic and biological peptide libraries that, in combination with high-throughput screening processes, has enhanced the prospects of obtaining new drug candidates, according to the author of the report, F&S research analyst Himanshu Parmar.
The approval of new peptide-based drug products such as Roche's HIV treatment Fuzeon (enfuvirtide) is stirring interest among many pharmaceutical companies. Globally, more than 40 peptide-based products are commercially available with six in the registration process. In Europe, about four to six peptide based products are in the market, with 100 in the clinical stage and 150 in advanced preclinical phases.
Peptides used in drug formulation and clinical trials account for nearly 93 per cent of the European therapeutic peptides market with R&D comprising the remainder. Almost 60 per cent of the market comprises peptide-based therapeutics for the oncology segment followed by cardiovascular, infection and metabolic therapeutics.
Despite the significant progress that has been made, technological challenges relating to the effective delivery of peptides, their instability in vivo and short half-life remain critical challenges. Costly and inefficient large-scale manufacturing and purification processes are, moreover, hampering market growth; Fuzeon itself has a massive 106 separate synthesis steps in its production, which has contributed to the hefty price tag for the drug.
The F&S report notes that priorities in research are to optimise peptide delivery inside cells, tissue organs or body, develop synthetic peptides with increased stability and half life and realising peptidomimetic molecules that duplicate the structural and functional properties of biologically active peptides but are smaller and easier to work with.
Meanwhile, it suggests that the development of cost-competitive, bulk manufacturing strategies are the key to sustained market expansion. "Modern and sophisticated formulation techniques, efficient and cost-effective scale up process and cutting-edge purification and separation methods with low cost and high throughput are fundamental to achieving high quality, economical products for commercial purposes," said Parmar.
Bachem is currently the leading manufacturer in the European therapeutic peptides market followed by UCB, PolyPeptide Laboratories, Peptisyntha and Diosynth. But other manufacturers are getting into the marketplace, including large chemical players like Clariant which recently started offering peptide manufacturing through an alliance with Indian company Jupiter Bioscience.
But escalating price sensitivity, competition and eroding prices are confronting all European manufactures. And as in the wider API sector, intensifying competition from low-cost Asian manufacturers by 2006-2007 is expected to trigger further price attrition in the peptide category.
"While manufacturers unable to compete on pricing will not be successful, they will also need to focus on competitive criteria such as quality, flexibility, reliability and implementation timeline," warned Parmar. "Additional strategies could include investing in process improvements, building manufacturing plants in low-cost areas, improving product and service portfolios to build customer loyalty and entering into strategic alliances with manufacturers and pharmaceutical companies."
Moreover, some manufactures could adopt a 'one-stop shop' strategy and develop a complete portfolio of therapeutic peptide products, while others could specialise by concentrating on a niche product area.
With a 33 per cent share in 2003, Germany led the European therapeutic peptides market closely followed by the UK with a 30 per cent share. Other important markets included Scandinavia, France, Italy and Spain.