Pelacarsen failed to meet its primary endpoint for reducing major cardiovascular events in the Phase 3 Lp(a)HORIZON trial, even though it effectively lowered Lp(a) levels, according to Ionis and Novartis.

The safety profile of pelacarsen was described as acceptable in the filing.

The Lp(a)HORIZON topline results come from a large trial enrolling 8,323 patients with established cardiovascular disease, randomized to pelacarsen or placebo.

Ionis stock and sentiment show a high forward earnings multiple around 91, reflecting growth expectations despite near-term volatility, with some view that the sell-off may be overdone.

Analysts note that despite the setback, Ionis could realize value over time as its fully owned therapies, including Dawnzera for hereditary angioedema, gain momentum outside the U.S.

Dawnzera posted a 63% sequential sales rise to $26 million in Q2 2026, as it expands beyond the United States, contributing to Ionis’ growth alongside Tryngolza and DAWNZERA’s ongoing progress.

Tryngolza was approved for severe hypertriglyceridemia in June and is advancing in familial chylomicronemia syndrome, with peak sales projected above $3 billion.

The development outlook will be influenced by potential changes to its development plan and how investors interpret future regulatory expectations.

Upcoming milestones, including the September FDA action date for zilganersen, keep market sentiment risk-off until clarity emerges.

Ionis’ near-term performance hinges on successfully executing remaining pipelines and launches to offset financial strain and preserve investor confidence.

Insider trading data show heavy selling by multiple executives over the past six months, with few purchases, potentially affecting investor perception.

The report is part of STAT’s exclusive coverage, suggesting deeper context behind the numbers may be available to subscribers.