Pivotal trial dossier · BioIntel

CORE-OLE: A Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Participants With Severe Hypertriglyceridemia (SHTG)

Ionis Pharmaceuticals, Inc. · Ph3 · NCT05681351 month only — not a planning date enrolment complete

Readout due

2027-03-01

Ph3

Patients

885

actual

Sites

262

33 countries

Arms

Masking

None

blinding depth

Design

Allocation	Na
Masking	None
Primary purpose	Treatment
Arms	1
Planned duration	51 months
Started	2022-12-13

What is being measured

Endpoint class	safety
Primary outcomes	3
Stated as	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 \| Proportion of Participants Who Experience Adverse Events (AEs) \| Proportion of Participants Who Use Concomitant Medications

Endpoint class is inferred from the sponsor's own wording of the primary outcome. Hard endpoints such as survival are generally harder to hit than scales or laboratory surrogates.

Population

Condition	Severe Hypertriglyceridemia
Therapeutic area	other
Patient pre-selection	all-comers (no selection detected)
Modality	small_molecule_or_unspecified
Sex	ALL

Evidence trail

Linked references	0 on the registry record
Results posted	not yet
Stopped early	no

Sponsor's recent catalyst filings

2026-09-23 — endpoint met 8-K
2026-09-23 — interim 8-K
2026-09-04 — topline 8-K
2026-09-04 — endpoint met 8-K
2026-09-04 — endpoint missed 8-K
2026-07-29 — breakthrough 8-K
2026-07-29 — pdufa 8-K

8-K events from this sponsor in the last 90 days. Context for how active and how newsworthy the company has been — not evidence about this trial.

Reference-class base rate

52% – 59%

historical share of Phase 3 trials in this class that reached approval

This is a base rate, not a prediction about this trial. It is what happened to comparable trials historically. It is not a model fitted on outcomes — no outcome labels exist for trials that have not read out — and it uses none of this trial's own results.

How this number was reached

No published Phase 3 rate for 'other'. Falling back to the all-area rate: 59.0% (Wong/Siah/Lo 2019) and 52.4% (BIO/Informa 2011–2020).

Design flags

• Not randomised.
• Runs in 33 countries. Multi-country trials show higher termination odds (OR 0.65).
• Enrolment is complete, so the readout date carries less recruitment risk.

Flags are shown separately rather than folded into the number. Wood et al. (BMJ 2008) measured effect-size inflation, not approval probability, so multiplying it into an approval rate would misuse the finding.

Deliberately not adjusted for

Enrollment size	no evidenced association with Phase 3 success
Number of sites	no evidenced association
Endpoint type	no evidenced association with success once area is held
Phase 2 design	single-arm vs randomised Phase 2 does not predict Phase 3

Each of these is visible in the registry and each is evidenced to be null for Phase 3 success. Using them would add false precision.

Evidenced, but not in the registry

Sponsor approval track record	51%→81% (Danzon 2005) — not a registry field
Orphan designation	aOR 2.3 — zero CT.gov fields carry FDA designations
Phase 2 effect-size shrinkage	rHR 0.73 — requires prior-trial results

The standing criticism, stated plainly. Hampson et al. (Pharmaceutical Statistics 2022;21(2):439–459, eight of nine authors at Novartis) argue that starting from industry rates and applying subjective adjustments "lacks transparency and fails to make full use of data from previous clinical trials". That criticism applies to this figure. The response here is to show every input and to refuse unsupported adjustments, not to claim the objection does not apply.

Rates: Wong, Siah & Lo, Biostatistics 2019 (CC BY 4.0; corrigendum values) and BIO/Informa/QLS Clinical Development Success Rates 2011–2020 (cited, not reproduced). MIT Project ALPHA is not used — its terms restrict use to governmental, charitable or social purposes and bar redistribution.