Please describe your practice as a clinician,how many patients with ATTR do you treat on a yearly basis? Could you walk us through the standard of care, and tell us a bit about the most promising upcoming treatments, or interesting clinical trials in this space.

What is your impression regarding Exploratory Endpoints Data, Including Cardiac Biomarkers and Imaging, and Impact of Patisiran on Measures of Cardiac Stress, Injury, Structure, and Function at Month 12 ?

Please comment on the 6 Minute Walk Test , Health Status and Quality of Life, as Measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ-OS), Compared to Placebo at Month 12 – result.

Please discuss the complete results:

• NT-proBNP adjusted geometric mean fold change from baseline at Month 12 was 1.11 for the patisiran group and 1.38 for the placebo group, with an adjusted geometric mean fold change ratio of 0.80 (nominal p equal to 1.825x10-5) in favor of patisiran.
• Troponin I adjusted geometric mean fold change from baseline at Month 12 was 1.13 for the patisiran group and 1.30 for the placebo group, with an adjusted geometric mean fold change ratio of 0.87 (nominal p=0.0011) in favor of patisiran.
• Results on several exploratory analyses of echocardiographic parameters at Month 12, including global longitudinal strain (p=0.0324), LV mass (p=0.0402), and LV end-diastolic volume (p=0.0508)
• Cardiac uptake of technetium on scintigraphy imaging was assessed in a planned cohort of patients, with 37 patients in the patisiran arm and 28 patients in the placebo arm evaluable at Month 12. Among evaluable patients with both baseline and Month 12 results (37 patisiran and 28 placebo), all patients in the patisiran arm (100%) reduced or demonstrated no change in the Perugini grading scale at Month 12 relative to baseline.
• Of the evaluable patients in the patisiran arm, 37.8% demonstrated a reduction of ≥1 Perugini grade, including 3 (8.1%) patients who reduced by ≥2 Perugini grades at Month 12. No evaluable placebo patients demonstrated a reduction from baseline in Perugini grade at Month 12.

Given that the APOLLO-B Phase 3 study showed positive results, with patisiran meeting the primary and first secondary endpoints, how do you reconcile these findings with the FDA's decision?

The FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 9:3 in favor of patisiran. What do you think about the main concerns or reservations of the three dissenting votes?

With the decision to no longer pursue an expanded indication for patisiran in the U.S., how does this impact the landscape of ATTR amyloidosis treatments?

Can you provide more insights into the ongoing HELIOS-B Phase 3 study of vutrisiran? What differentiates it from patisiran, and what are the company's expectations for this study?

How do you feel about ALN-TTRsc04 and its potential for greater TTR knockdown with once annual dosing?