Acuity files first therapeutic siRNA IND
therapeutic based on small interfering RNA (siRNA) - for the wet
form of the eye disease age-related macular degeneration - has been
filed by Acuity Pharmaceuticals.
The news also raises the prospect of using siRNA as a viable treatment, not only for wet AMD but also diseases caused by inappropriate activity of specific genes. The ability to silence and regulate such genes selectively through siRNA could provide an essential tool for drug discovery and therapeutic development.
The application focuses on using siRNA to treat macular degeneration of the eye, a leading cause of blindness, as well as other ocular diseases caused by abnormal growth or leakage of small blood vessels in the eye.
The siRNA lead product candidate, Cand5, is to undergo Phase I clinical trials to test its mechanism of RNA interference (RNAi) to shut down genes that promote the overgrowth of blood vessels that lead to vision loss in wet AMD.
Cand5's mechanism of action shuts down the production of vascular endothelial growth factor (VEGF), the central stimulus in the development of wet AMD. This is achieved by using short nucleic acid sequences that bind to and inactivate the machinery in the cell that leads to protein transcription. This is also known as gene silencing and its manner is similar to that achieved using antisense oligonucleotides.
Dale Pfost, president and CEO of Acuity, said: "This powerful technology has the potential to treat many diseases with greater efficacy and safety than current approaches."
Pending review by the FDA, Phase I studies are scheduled to commence in September.
Lawrence Yannuzzi, clinical professor of ophthamology at Columbia University added: "Treatments based on harnessing RNAi to shut down production of VEGF may offer an entirely new approach to treating AMD."
siRNA has emerged as a valuable tool for drug discovery and research but, as with antisense before it, difficulties in getting the compounds to where they are needed in the body has held back its development as a therapy.
However delivering drugs into the eye is relatively simple - this is why the first and only antisense treatment approved to date is for an eye disease.
The prospects of a siRNA-based drug reaching the market seem encouraging especially as several biotech firms are currently working on similar treatments.
Alnylam Pharmaceuticals established a strategic collaboration with Merck to develop and commercialise ophthalmic drugs including one for AMD. The company expect to advance this program into clinical trials in 2005.
More than 1.6 million adults over the age of 50 in the US currently suffer from advanced AMD, a condition that causes severe deterioration of vision and may ultimately cause blindness.
