Long-term Safety of Eplontersen Treated aTTR Patients and in Liver Transplant and Severely Hepatic Impaired Subpopulations

• Prevalence of liver transplant prior to eplontersen initiation (overall by reason for liver transplant),
• Prevalence of severe hepatic impairment prior to eplontersen initiation These will be summarised as prevalence proportion and 95% CI. Secondary outcomes: Demographic characteristics (e.g. age, sex), general health factors (e.g. BMI), indication related characteristics (e.g. ATTR diagnoses dates and duration since first diagnosis, type, severity), prior and concomitant medications (as part of standard care of ATTR at eplontersen initiation), pre-existing and concurrent relevant morbidities will be described using descriptive statistics of counts, proportions and/or distribution characteristics (mean (SD), median (range)).

Onset of new clinical events, abnormal laboratory values, serious adverse events will be analysed as follows:

a) Counts and frequency of first events and total number of events, incidence rate and incidence risk of events per time periods (e.g., 0-6, 7-end of follow-up available at time of reporting). b) Cohort event monitoring analysis including a. Incidence densities per 6 months (in the first year) or 12-months (after one year) intervals will be estimated. b. Differences in incidence densities per 6 or 12months intervals c. Nelson-Aalen estimator of cumulative hazard rate function over time. c) For SAEs, qualitative case reports of clinical course and patients' characteristics and comorbidities will be provided.

These outcomes are all relative to primary objective 2 of study and are all relative to the same outcome measure.

To describe eplontersen treatment use, including duration of treatment and reasons for discontinuation (overall, in patients with prior liver transplant, in patients with pre-existing severe hepatic impairment). These outcomes are all relative to secondary objective 1 of the study which is to describe "eplontersen treatment use".

Same as primary objective 2, separately in i) patients with prior liver transplant and ii) patients with pre-existing severe hepatic impairment. These outcomes are relative to primary objective 2 of the study and to the same outcome measure, i.e. "long-term safety in patients who initiated eplontersen treatment". This is a long-term safety study without a prespecified adverse event of interest; therefore, all safety events are in scope, as defined in the protocol: all serious adverse events identified; other adverse events, including any new diagnosis reported as a co-morbidity, new sign or symptom, or new abnormal laboratory value within 115 days of last eplontersen dose. To support systematic and comprehensive listing of all AEs, clinical data in D8450R00003, in addition to serious adverse events, will be coded using MedDRA. Clinical data that cannot be mapped to MedDRA will also be considered.