Despite the global economic downturn, CMOs and producers of oligonucleotides for research, therapeutic, and diagnostic applications remain optimistic that the healthy growth rate enjoyed over the past few years will continue. While some drug companies may delay development projects until the economy turns around, oligo producers appear confident that they will weather this uncertain period and maintain a steady flow of projects.
Driving this continued growth and optimism is the combination of the maturing market for DNA therapeutics—with several products in or near late-stage development—the growing demand for oligo-based molecular diagnostic products, and the dramatic rise in RNA interference (RNAi) applications in academia and industry, including small interfering RNAs (siRNA), microRNAs (miRNA), and newly emerging RNA classes.
“We have seen an increase in our sales over the same time last year,” says John Bremner, Ph.D., business development director at Link Technologies, which specializes in manufacturing products for the synthesis of modified oligonucleotides. He describes a general increase in demand for both DNA and RNA products, with a notable surge in interest in RNA.
Link is currently developing a number of RNA modifiers and, in Dr. Bremner’s view, “I think we will begin to see modifications becoming more important for RNA.” As projects in industry mature, the need for modified oligos is moving into large-scale production. Dr. Bremner notes a particular interest in amino and cholesterol modifiers, the latter being particularly attractive for cell delivery.
Additionally, as oligo therapeutics move through drug development pipelines, regulatory and safety concerns become paramount. “We are responding to an increasing demand for products that are BSE and TSE encephalopathy-free,” says Dr. Bremner. “Cholesterol is a molecule that could potentially cause problems, and therefore we have now switched to an entirely vegetable source, derived from a Mexican yam.”
Even with the economic slowdown, “we are still seeing heavy demand for oligos,” says Kathryn L. Ackley, Ph.D., director of operations at Girindus America, a manufacturer of oligo APIs for preclinical through commercial-scale applications. This demand spans oligo classes and is particularly notable for oligos with 2´ modifications, conjugated oligos, and siRNA, she notes.
Girindus has the capacity to produce hundreds of kilograms of oligos a year following completion of its $5.2 million expansion program, which doubled its oligo manufacturing space. The company also offers in-house radiolabeling of oligos.
Agilent Technologies has compiled substantial data documenting trends in oligo therapeutics programs. The data demonstrates a more than doubling of the number of programs between 2003 (103) and 2009 (231). Antisense represents the most mature sector, with the largest percentage of products in clinical development, followed by immunostimulatory oligos. Cancer and infectious disease indications account for 48% of therapeutic oligo programs, with cardiovascular, renal, respiratory, and ocular also large segments.
Agilent reports that direct investment in oligo therapeutics rose from $268 million in 2002 to $971 million in 2007, dipping to $682 million in 2008. The total potential deal value of collaborations soared from $7 million in 2003 to more than $6 billion in 2008.