Lonza teams up with RNA-TEC for oligo production
active pharmaceutical ingredients, has forged a collaboration with
RNA-TEC of Belgium to provide broad-ranging contract production of
oligonucleotides, a new class of drug that looks set to explode
onto the marketplace in the next few years, reports Phil
Taylor.
Lonza has been active in contract oligonucleotide manufacture for some time, but the agreement with RNA-TEC brings the companies the capability to offer both intermediate- and large-scale production capacities, allowing companies to take their projects from the preclinical stage right through to commercial production.
Oligonucleotides, also referred to as antisense drugs, have taken a long time to fulfil their potential. The first drug in the class was Isis Pharmaceuticals' Vitravene (fomivirsen) for cytomegalovirus retinitis, an opportunistic infection in patients with AIDS. This was launched in 1998 and licensed to Novartis, but failed to take off because its market shrank as more effective drugs were launched to control HIV infection.
Since then, not a single oligonucleotide-based treatment has reached the market, but this is all set to change. Researchers have overcome one of the primary barriers to the adoption of the technology, its systemic delivery (Vitravene required injection into the eyeball), and a new generation of antisense drugs are nearing the market.
Meanwhile, following on behind is an even newer technology - small interfering RNA (siRNA) - that is generating considerable excitement in drug discovery circles. siRNA can be used to selectively switch off gene function, although delivery is still a major issue for this class.
Lonza and RNA-TEC are gearing up to take advantage of this industry trend and provide manufacturing capacity for oligos in anticipation of this new wave of drugs.
The two companies will combine their RNA synthesis expertise, providing RNA-oligonucleotides ranging from intermediate scale, manufactured by RNA-TEC, up to industrial quantities, manufactured under current Good Manufacturing Practice (cGMP) conditions by Lonza at its Visp site in Switzerland.
At the heart of the collaboration is the TBDMS technology, a method of synthesising and purifying oligos which is particularly suited to intermediate- and large-scale production, according to Johan de Schepper, RNA-TEC's chief executive.
He told DrugResearcher.com that while TBDMS has been somewhat superceded by other technologies for small-scale oligo production - developed by Qiagen and Dharmacon - these are not the best options once production is hiked to the intermediate scale i.e. the production of oligos for animal experiments.
"TBDMS is resurfacing as a more effective means of synthesising and purifying product at this scale," he said.
At present, there are few players in the intermediate-scale production category, he said, unlike the small-scale sector which is dominated by the two top-ranked companies Qiagen and Dharmacon as well as Degussa subsidiary Proligo and Ambion.
"Once the amounts scale-up, competition gets thin," said de Schepper, although he noted that both Dharmacon and Proligo seem to have ambitions in this area. The key to success is not hinged on technology but expertise in the use of equipment and protocols, he suggested, noting that the collaboration between Lonza and RNA-TEC is based on this premise.
Looking at the development of the marketplace, de Schepper has a healthy cynicism about the potential of the therapeutic marketplace for RNA-based therapeutics, at least in the short term. While this sector is very promising (and indeed accounts for the lion's share of RNA-TEC's intermediate-scale synthesis business), he believes that siRNA used for target validation and other research purposes will be the major driver for the market over the next few years.
Nevertheless, a recent report from Urch Publishing notes 23 oligo-based therapeutics are in clinical trials, including four in Phase III trials. The next few years should witness the launches of Genta's Genasense (oblimersen sodium) and Isis' Affinitak (ISIS 3521) for cancer, Isis' alicaforsen (ISIS 2303) for Crohn's disease and an E2F decoy from Corgentech for arterial graft survival.
Meanwhile, estimates for the overall size of the market for contract biologics manufacture are $1.3 billion in 2003 - out of a total contract biopharma production market of $4 billion - and should increase to $1.7 billion in 2004, according to data from market research firm BioPlan.
