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Olezarsen

Phase 3

Familial Chylomicronemia Syndrome | RNA therapy | Rare Disease |Ionis Pharmaceuticals, Inc.|Last Updated: Aug 26, 2026

Target and mechanism

Molecular targetAPOC3
Target classAntisense Inhibitor
ModalityRNA therapy

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials4
Total Enrollment162

FDA Designations

PRIORITY_REVIEWORPHAN_DRUGFAST_TRACKBREAKTHROUGH_THERAPY

Clinical trial landscape

Olezarsen · 10 trials · 7 indications

Phase 3 8Phase 2 1Phase 1 1
NCT07727538A Study of Olezarsen for the Treatment of Familial Chylomicronemia Syndrome (FCS) in Pediatric ParticipantsFamilial Chylomicronemia Syndrome
RECRUITING12 Analytics
NCT05681351CORE-OLE: A Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Participants With Severe Hypertriglyceridemia (SHTG)Severe Hypertriglyceridemia
ACTIVE NOT_RECRUITING885 Analytics
NCT05610280A Study of Olezarsen (ISIS 678354) in Participants With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease, or With Severe HypertriglyceridemiaHypertriglyceridemia
COMPLETED1,478 Analytics
NCT05552326A Study of Olezarsen Administered Subcutaneously to Participants With Severe HypertriglyceridemiaSevere Hypertriglyceridemia
COMPLETED446 Analytics
NCT05185843A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRX) Administered to Adults With Familial Chylomicronemia Syndrome (FCS) Previously Treated With VolanesorsenFamilial Chylomicronemia Syndrome
ACTIVE NOT_RECRUITING24 Analytics
NCT05130450A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) in Participants With Familial Chylomicronemia Syndrome (FCS)Familial Chylomicronemia Syndrome
ACTIVE NOT_RECRUITING60 Analytics
NCT05079919A Study of Olezarsen (ISIS 678354) Administered to Participants With Severe HypertriglyceridemiaSevere Hypertriglyceridemia
COMPLETED617 Analytics
NCT04568434A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) Administered to Patients With Familial Chylomicronemia Syndrome (FCS)Familial Chylomicronemia Syndrome
COMPLETED66 Analytics
PHASE3RECRUITING
A Study of Olezarsen for the Treatment of Familial Chylomicronemia Syndrome (FCS) in Pediatric Participants
Familial Chylomicronemia SyndromeUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
CORE-OLE: A Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Participants With Severe Hypertriglyceridemia (SHTG)
Severe HypertriglyceridemiaUnlock trial analytics
PHASE3COMPLETED
A Study of Olezarsen (ISIS 678354) in Participants With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease, or With Severe Hypertriglyceridemia
HypertriglyceridemiaUnlock trial analytics
PHASE3COMPLETED
A Study of Olezarsen Administered Subcutaneously to Participants With Severe Hypertriglyceridemia
Severe HypertriglyceridemiaUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRX) Administered to Adults With Familial Chylomicronemia Syndrome (FCS) Previously Treated With Volanesorsen
Familial Chylomicronemia SyndromeUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) in Participants With Familial Chylomicronemia Syndrome (FCS)
Familial Chylomicronemia SyndromeUnlock trial analytics
PHASE3COMPLETED
A Study of Olezarsen (ISIS 678354) Administered to Participants With Severe Hypertriglyceridemia
Severe HypertriglyceridemiaUnlock trial analytics
PHASE3COMPLETED
A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) Administered to Patients With Familial Chylomicronemia Syndrome (FCS)
Familial Chylomicronemia SyndromeUnlock trial analytics

Study Endpoints

Primary Endpoints

Percent Change from Baseline in Fasting Triglycerides (TG)
At 6 Months
Proportion of Participants With Change in Clinical Laboratory Values From Baseline to Week 53, From Baseline to Week 105, and From Baseline to Week 157
Baseline up to Week 157
Proportion of Participants Who Experience Adverse Events (AEs)
Baseline up to Week 157
Proportion of Participants Who Use Concomitant Medications
Baseline up to Week 157
Percent Change From Baseline to Week 25 in Fasting Triglycerides (TG) Compared to Placebo
Baseline to Week 25
Percent Change from Baseline in Fasting TG Compared to Placebo
Baseline and Month 6
Proportion of Participants With Decrease in Platelet Count by >30% or >50%, or With Platelet Count Value <50,000/cubic millimeter (mm^3)
Baseline to Week 209
Proportion of Participants With Clinical Bleeding Events
Baseline to Week 209
Proportion of Participants With Decrease in Estimated Glomerular Filtration Rate (eGFR) by ≥30% or ≥50%
Baseline to Week 209
Proportion of Participants With Urine Protein/Creatinine Ratio (UPCR) ≥1000 milligram (mg)/gram (g) or with Urine/Albumin Creatinine Ratio (UACR) ≥500 mg/g
Baseline to Week 209
Proportion of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥5 x Upper Limit of Normal (ULN)
Baseline to Week 209
Proportion of Participants With ALT or AST ≥3 x ULN and Total Bilirubin > 2 x ULN
Baseline to Week 209
Proportion of Participants With Total Bilirubin ≥2 mg/deciliter (dL)
Baseline to Week 209
Percent Change From Baseline in Fasting TG at 6 Months (Average of Weeks 23, 25, and 27) Compared to Baseline
Baseline and 6 months
Percent Change From Baseline in Fasting TG at Month 6
Baseline, Month 6
Area under the plasma concentration-time curve (AUC) of olezarsen from time 0 to 336 hours (AUC0-336h)
Up to Day 8 of each of Treatment Periods 1 and 2
Maximum plasma concentration of olezarsen (Cmax)
Up to Day 91 of Treatment Period 2

Secondary Endpoints

Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Including Independently Adjudicated Events of Pancreatitis, and Withdrawals due to Adverse Events (AEs)
Up to 24 Months
Change From Baseline in Vital Sign Parameter - Heart Rate (Beats per Minute)
Baseline up to 24 Months
Change From Baseline in Vital Sign Parameter - Blood Pressure (Systolic and Diastolic, mmHg)
Baseline up to 24 Months
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Study Design & Arms

AllocationNA
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Cohort 1EXPERIMENTALParticipants aged 12 to \<18 years will receive multiple doses of olezarsen, at a dose level that depends on body weight, once every month by subcutaneous injection for up to 1 year. All participants may continue to the optional 1-year long-term extension period with the last dose received being after 2 years of treatment.
Cohort 2EXPERIMENTALParticipants aged 2 to \<12 years will receive multiple doses of olezarsen, at a dose level based on information obtained from Cohort 1, once every month by subcutaneous injection for up to 1 year. All participants may continue to the optional 1-year long-term extension period with the last dose received being after 2 years of treatment.
OlezarsenEXPERIMENTALParticipants who completed either ISIS 678354-CS5 (NCT05079919) or ISIS 678354-CS6 (NCT05552326) study would be enrolled to receive olezarsen, subcutaneous (SC) injection, once every 4 weeks from Week 1 through Week 153.
PlaceboPLACEBO_COMPARATORParticipants will be randomized to receive olezarsen-matching placebo, once every 4 weeks by SC injection up to Week 49.
Olezarsen 50 mgEXPERIMENTALParticipants received olezarsen, 50 milligrams (mg), once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Olezarsen 80 mgEXPERIMENTALParticipants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Olezarsen Dose Level 1EXPERIMENTALParticipants will receive two doses of Dose Level 1 each, using one of the following two sequences: (i) AI on Day 1 of Treatment Period 1, followed by vial on Day 1 of Treatment Period 2; or (ii) vial on Day 1 of Treatment Period 1, followed by AI on Day 1 of Treatment Period 2. A washout period of 28-42 days will be maintained between the 2 treatment periods.
Olezarsen Dose Level 2EXPERIMENTALParticipants will receive two doses of Dose Level 2 each, using one of the following two sequences: (i) AI on Day 1 of Treatment Period 1, followed by vial on Day 1 of Treatment Period 2; or (ii) vial on Day 1 of Treatment Period 1, followed by AI on Day 1 of Treatment Period 2 A washout period of at least 28 days will be maintained between the 2 treatment periods.

Interventions

NameTypeDescription
OlezarsenDRUGOlezarsen will be administered by subcutaneous injection.
PlaceboDRUGOlezarsen-matching placebo will be administered by SC injection.
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Eligibility Criteria

Age Range2 Years to 17 Years
SexALL
Healthy VolunteersNo
Study Sites4

Key Inclusion Criteria: 1. Parental or legally authorized representative consent must be obtained, and the participants must provide age-appropriate or cognition-appropriate assent, as determined by the Investigator. The parent or legal guardian must be able to understand and comply with the study ...

Countries:United StatesArgentinaAustraliaBelgiumBrazilBulgariaCanadaCzechiaDenmarkFinlandFranceGermanyGreeceHungaryIndiaIsraelItalyLithuaniaMalaysiaMexicoNetherlandsNew ZealandNorwayPolandPortugalRomaniaSlovakiaSouth AfricaSpainSwedenTaiwanTurkey (Türkiye)United Kingdom
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Recent Changes (Last 90 Days)

LOWAug 26, 2026NCT07727538lastUpdatePostDate: changed
LOWAug 26, 2026NCT07727538lastUpdatePostDate: changed
LOWAug 18, 2026NCT07727538startDate: changed
LOWAug 18, 2026NCT07727538startDate: changed
LOWJul 29, 2026NCT07727538lastUpdatePostDate: changed
LOWJul 29, 2026NCT07727538lastUpdatePostDate: changed
LOWJul 27, 2026NCT07727538NEW_TRIAL: changed
LOWJul 27, 2026NCT07727538NEW_TRIAL: changed
LOWJul 27, 2026NCT07727538NEW_TRIAL: changed

Frequently asked questions about Olezarsen

What is Olezarsen?

Olezarsen is an investigational RNA therapy developed by Ionis Pharmaceuticals for lowering triglyceride levels in metabolic and cardiovascular conditions. It is being studied in familial chylomicronemia syndrome, hypertriglyceridemia, and severe hypertriglyceridemia. It has received FDA designations including Priority Review, Orphan Drug, Fast Track, and Breakthrough Therapy.

What is Olezarsen used for?

Olezarsen is being developed to treat familial chylomicronemia syndrome and hypertriglyceridemia, including severe hypertriglyceridemia, and is also being studied in patients with hypertriglyceridemia and atherosclerotic cardiovascular disease. It is an investigational therapy and has not been established as safe or effective for any indication.

What does Olezarsen target?

Olezarsen targets apolipoprotein C-III, or APOC3. It is an antisense inhibitor designed to reduce production of APOC3, a protein involved in regulating plasma triglyceride levels. By lowering APOC3, the therapy aims to reduce triglycerides in patients with elevated levels.

Who makes Olezarsen?

Olezarsen is developed by Ionis Pharmaceuticals, Inc., which trades on the Nasdaq under the ticker IONS. Ionis is the sponsor of the clinical development program for the drug across familial chylomicronemia syndrome and hypertriglyceridemia indications.

What phase is Olezarsen in?

Olezarsen is in Phase 3 clinical development. It is an investigational drug and has not been approved by the FDA. The program includes Phase 3 trials in severe hypertriglyceridemia and hypertriglyceridemia with atherosclerotic cardiovascular disease, plus a Phase 3 pediatric study in familial chylomicronemia syndrome.

What clinical trials is Olezarsen in?

Olezarsen trials include NCT05681351, a Phase 3 study in severe hypertriglyceridemia; NCT05610280, a completed Phase 3 study in hypertriglyceridemia and atherosclerotic cardiovascular disease or severe hypertriglyceridemia; NCT07727538, a recruiting Phase 3 pediatric study in familial chylomicronemia syndrome; and NCT05579860, a completed Phase 1 study in healthy participants.

Is Olezarsen the same as ISIS 678354?

Yes. Olezarsen is also known as ISIS 678354, and both names refer to the same investigational antisense inhibitor targeting APOC3. Trial records for the Phase 3 severe hypertriglyceridemia and hypertriglyceridemia studies list the drug under the ISIS 678354 designation.