Importantly, the data from the phase II open-label extension study provided strong evidence that the underlying SNALP LNP delivery technology, licensed from Tekmira Pharmaceuticals, is safe and well tolerated with 19 of the 27 patients involved having now received ALN-TTR02 once every 3 weeks for at least 6 months. After 282 doses administered, no drug-related serious adverse events were seen with infusion-related issues as expected the main source of adverse events. Notwithstanding the 8 mild flushing events and infusion reactions, there have been no drop-outs in the study so far.
On the efficacy side, ALN-TTR02 continued to produce robust sustained 80-90% knockdowns with a trend towards increased knockdown efficacy with prolonged dosing. This knockdown certainly puts ALN-TTR02 ahead of the competitor antisense drug from ISIS and GSK (ISIS-TTRRx) which is expected to be in the 70% range, but is probably ahead in terms of patient enrolment in their pivotal study.
The results presented at the ANA conference had been widely anticipated because it was the first time that Alnylam revealed measures of therapeutic efficacy beyond the gene knockdown. Accordingly, at the 6-month time-point patients treated with ALN-TTR02 exhibited less neurological declines as would have been expected from the Natural History of the disease. Unfortunately, in the absence of hard biomarker evidence indicating improved neurological and, for a subset of patients, cardiac functions, the apparent improvement in the well-being of the patients (mNIS+7) could easily be attributed to the open-label nature and the relatively early time-point of the study.
Therefore, despite of the fact that shares in Alnylam increased 20% on the results and the provider of the delivery technology, Tekmira, barely budged on the news, the most important take-home from the results was that SNALP LNP delivery technology and indeed extended robust RNAi has a remarkably good safety profile.