You will see this theme continue: Systemic RNAi delivery technologies that have proven themselves in non-human primate and clinical studies will continue to yield pipeline candidates and attract potential partners. Today’s announcement by Alnylam at the Annual OTS Meeting that it has chosen SNALP-enabled ALN-APC targeting the liver-expressed Protein C in hemophilia as its 5x15TM development candidate no. 4 confirms this.
As a reminder, and despite of Alnylam’s claims of SNALP being only one of its many systemic delivery options, all four of Alnylam’s nominated 5x15TM candidates are based on Tekmira’s SNALP technology, which also means that 5 out of 6 of Alnylam’s development candidates are SNALP-based (in temporal order): ALN-VSP02, ALN-TTR, ALN-PCS, ALN-HPN, ALN-APC. Only Alnylam’s (historical) first candidate, the aerosolized naked and unmodified ALN-RSV01 is not a SNALP product. Add to this Tekmira’s own TKM-ApoB, TKM-PLK1, and TKM-EBOLA development candidates, and one can see the promise of RNAi Therapeutics become reality [correction September 9, 2011: the Huntington's program should have been noted here, although that one in some regards is quite similar to ALN-RSV01].
ALN-APC is indicated for the treatment of hemophilia patients, especially those that have developed resistance to their first-line therapy in the form of inhibitory antibodies against their recombinant protein replacements. As activated Protein C shifts the hemostatic balance towards bleeding, knocking this exclusively liver-expressed gene down is predicted to reduce the propensity of hemophilia patients to bleed. This, importantly, is also suggested by human genetics as there are apparently hemophilia patients that have a genetic resistance against or deficiency in Protein C, and consequently have less frequent bleeding compared to hemophilia patients without these concomitant mutations. Boding well for the safety of this approach, especially a concern when one starts to meddle with coagulation, these patients do not have a known increased risk of thrombosis.
Tekmira’s SNALP technology, as predicted based on strong science, is leading the way in this pipeline expansion paradigm by targeting particularly liver, but also solid tumor-expressed genes in a variety of diseases. The only other systemic RNAi delivery technology that has about reached the stage where one can feel comfortable similarly entering new pipeline candidates is Silence Therapeutics’ Atuplex technology for knocking down genes in vascular endothelial cells.
RNAi Therapeutics development does not have to be complicated. The simple trick is to let science lead the way…