Ionis Pharmaceuticals Shares Fall After Pelacarsen Phase 3 Trial Misses Primary Endpoint

Ionis Pharmaceuticals (NASDAQ:IONS) shares fell 13.1% to $50.51 in premarket trading as investors continued to assess the Phase 3 trial result for pelacarsen, an RNA-targeted cardiovascular drug licensed to Novartis.

Novartis disclosed on September 4 that the Phase 3 Lp(a)HORIZON study did not meet its primary endpoint. The trial enrolled more than 8,300 high-risk patients over six years and evaluated whether pelacarsen could reduce cardiovascular events compared with placebo.

Pelacarsen lowered lipoprotein(a), or Lp(a), levels, but the study did not demonstrate a statistically significant reduction in the composite endpoint of cardiovascular death, heart attack, stroke and urgent coronary revascularisation.

Trial Result Affects Potential Ionis Payments

Ionis licensed pelacarsen to Novartis under an agreement that included potential commercial payments linked to the drug’s development and sales.

Under the 2019 licensing agreement described in the supplied information, Ionis was eligible for tiered royalties ranging from the mid-teens to low-20% of net sales, as well as up to $650 million in development, regulatory and commercial milestone payments.

The Phase 3 result reduces the prospects for commercial payments associated with pelacarsen under its existing development programme. The supplied information does not provide an updated estimate from Ionis or Novartis of the remaining payments that could become due under the agreement.

The trial outcome also provides additional clinical evidence for companies developing therapies designed to lower Lp(a). However, the result for pelacarsen does not by itself establish the outcome of other treatments targeting Lp(a).

Analysts Assess Impact on Ionis Pipeline

Citi analysts acknowledged the pelacarsen result but said they viewed the immediate downside for Ionis as limited because of the company’s broader development pipeline, according to the supplied information.

Separately, another analyst maintained a Buy rating and a $100 price target, assessing the Lp(a)HORIZON result as a setback that did not alter the analyst’s broader view of Ionis.

These ratings and assessments represent analysts’ opinions and do not establish the company’s future financial or clinical performance.

Previous Eplontersen Trial Also Missed in 2026

The pelacarsen result follows a separate Phase 3 cardiovascular trial involving eplontersen that did not meet its objective in July 2026, according to the supplied information.

Ionis shares were trading close to their 52-week low of $50.01 in Tuesday’s premarket session and below their 52-week high of $86.74.

The broader U.S. market showed comparatively limited movement, with the S&P 500 down 0.2%, the Dow Jones declining 0.7% and the Nasdaq up 0.1%.

Ionis also has other programmes in its portfolio, including the recently approved ZANVASTRO and zilganersen, which has a PDUFA target action date of September 22.

Investors are assessing those programmes alongside the implications of the Lp(a)HORIZON result for potential pelacarsen-related payments and Ionis’s broader development portfolio.

Ionis Pharmaceuticals stock price