The purpose of this study is to evaluate the effect of olezarsen (formerly known as AKCEA-APOCIII-LRx) on the percent change in fasting triglycerides (TG) from baseline.

This is a multi-center, open-label extension (OLE) study of up to 60 participants with FCS rolling-over from Study ISIS 678354-CS3 (NCT04568434). Participants will receive olezarsen during a 157-week treatment period, followed by a 13-week post-treatment follow-up period. The length of participation in this study is approximately 201 weeks, which includes an up to 31-day qualification period, a 157-week treatment period, and a 13-week post-treatment evaluation period.

Treatment has been extended to obtain additional safety assessments and efficacy data and to provide patients with continued access to ISIS 678354 until the drug may be available commercially.

Inclusion Criteria:

• Satisfactory completion of treatment with olezarsen in the index study (ISIS 678354-CS3, last dose as scheduled at Week 49) with an acceptable safety profile, per Investigator judgement.

Exclusion Criteria:

• Have any new condition or worsening of existing condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the patient participating in or completing the study, including need for treatment with medications disallowed in the index study (ISIS 678354-CS3).

Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.