Clinical Data The APOLLO Phase 3 trial is a randomized, double-blind, placebo-controlled, global study designed to evaluate the efficacy and safety of patisiran in patients with FAP. The primary endpoint of the study is the difference in the change in a modified neuropathy impairment score, "mNIS+7," from baseline to 18 months between patisiran and placebo. mNIS+7 measures disease progression including muscle weakness, impaired reflexes, and changes in other sensory measures. Secondary study endpoints include: the Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) score; modified body mass index (mBMI); timed 10-meter walk; an autonomic symptom score called "COMPASS-31," amongst other endpoints. In addition, nerve regeneration by measurement of sweat gland nerve fiber density will be assessed in patients who elected to provide skin punch biopsy samples. The study was significantly over-enrolled with a total of 225 FAP patients with Stage 1 or Stage 2 disease, compared to the original anticipated enrollment of 200. Patients were randomized 2:1 (patisiran:placebo) with patisiran administered at 0.30 mg/kg once every three weeks for 18 months. The study was designed with 90% power to conservatively detect as little as a 37.5% difference in change in mNIS+7 between treatment groups, with a two-sided alpha of 0.05. The expected placebo mNIS+7 progression rate of 24 points over 18 months was derived from an analysis of natural history data from 283 FAP patients (Adams et al., Neurology, 2015;85:675-682). All patients completing the APOLLO Phase 3 study are eligible to enroll in the ongoing APOLLO Phase 3 open-label extension (OLE) study (APOLLO-OLE).In an ongoing Phase 2 OLE study of patisiran in FAP patients (N=27) with similar baseline characteristics, patisiran administration was associated with a mean increase in mNIS+7 of just 1.7 points over 18 months in the 20 patients that had reached that timepoint as of the data cutoff. The ongoing Phase 2 OLE study has provided initial evidence that patisiran has the potential to halt neuropathy progression in FAP patients, including the first-ever evidence for positive effects on nerve regeneration. Patisiran administration was also found to be generally well tolerated in FAP patients out to nearly two years, with minimal drug-related adverse events reported.