Galapagos has used its SilenceSelect adenoviral siRNA platform to discover and validate novel drug targets that may affect bone remodelling. Wyeth has now selected a set of these targets for internal development, triggering a financial milestone for Galapagos.
Under the terms of the agreement, Wyeth now have 15 months to work on the selected drug targets after which they have the choice to license the compound and engage in further research.
This collaboration is set to make a significant impact on the osteoporosis treatment market. Currently, there are no anabolic drugs on the market that enable re-strengthening of the bone following initial diagnosis. The need for an effective osteoporosis drug has been growing worldwide every year with a 3-fold increase in female incidences when compared to males with the elderly being our target group.
Osteoporosis is principally a disease of middle age during which hormone levels essential for maintaining bone density decline. The development of osteoporosis is characterized by a clinically significant reduction in mean bone density due to an increase in bone resorption.
The disease is four times as common in women than men. The enormous health care costs associated with osteoporosis, estimated at $15 billion in the USA, are related to the greatly increased incidence of fractures in osteoporosis patients.
Whereas most current therapies have an anti-resorptive mechanism of action, agents with bone-forming properties can be identified for future therapies by identifying targets and molecules with anabolic functions and actions.
Onno van de Stolpe, CEO of Galapagos told DrugResearcher.com: "Wyeth has selected certain drug targets that play a part in bone structure, that have been validated in vivo via assays."
"The SilenceSelect and FleXSelect platforms are screened in this assay to identify drugable targets that promote specifically osteoblast formation and bone deposition. These hits are then validated through a selection of secondary validation assays, in order to select a final set of high value novel drugable osteoporosis targets for compound screening."
The SilenceSelect technology uses adenoviral-siRNA technology, which knocks-down the expression of selected genes in human cells. Genes in the drugable classes are of specific interest to the pharmaceutical industry as the proteins encoded by these genes are potential targets for small molecule intervention.
However, these tools have limited usefulness in studies in primary cells due to inefficient transfection of the active molecules. In order to perform genome-wide function screening using siRNA technologies in primary cell systems, more robust transfection with longer-term knock-down is needed.
Van de Stolpe commented: "Galapagos' siRNA approach involves an adenovirus, which has the significant advantage of producing siRNA for weeks on end. The other preferred technique, direct siRNA transfection can only produce siRNA for only eight hours."
He said that he expected a drug to treat osteoporosis to hit the market in 7-8 years providing everything went according to plan.
Current therapeutic strategies are focused on the bisphosphonate compounds such as alendronate (Fosamax) and risedronate (Actonel), and the selective estrogen receptor modulators such as raloxifene (Evista). All have been shown to inhibit bone resorption and therefore decelerate bone loss and decrease fracture.
US based company, Alnylam are currently working on a pipeline of RNAi therapeutics that will be administered directly at sites of diseases, such as the eye or the brain with a view to developing a range of RNAi therapeutics that travel through the bloodstream and can be used to treat a broad range of diseases.