Ionis Trial Failure
Ionis Stock Tumbles as Trial Fails Primary Endpoint, Analysts See Long-Term Value
Key Points
In the CARDIO-TTRansform trial, a subset of patients not on baseline stabilizers showed a hazard ratio of 0.71 for cardiovascular events with eplontersen, indicating potential benefit in monotherapy conditions.
A large portion of trial participants were on stabilizer therapy at baseline (57%), with an additional 24% initiating stabilizers during the trial, complicating interpretation of overall efficacy.
Eplontersen was described as well tolerated with a favorable safety profile that was consistent with prior results, suggesting the failure was not driven by safety concerns.
Stifel’s commentary highlighted that Ionis now trades with a Hold rating while Alnylam remains rated Buy, reflecting a shift in valuation emphasis and noting Alnylam’s momentum despite the broader market impact.
Ionis Pharmaceuticals shares collapsed 23% on Thursday after its heart drug eplontersen failed a major Phase 3 trial, wiping out roughly $3 billion in market value, according to ts2.tech. The drug, sold as Wainua in partnership with AstraZeneca, missed its primary endpoint in the CARDIO-TTRansform trial for a deadly heart condition called transthyretin amyloid cardiomyopathy, or ATTR-CM.
The selloff hit AstraZeneca too, while rivals Alnylam and BridgeBio rose on hopes that a key competitor may be stepping back from the ATTR-CM market. Analysts scrambled to cut price targets, though several still see long-term value in Ionis.
Why the Trial Failed to Impress the Market
The CARDIO-TTRansform trial enrolled a wide mix of patients. At baseline, 57% of participants were already on stabilizer therapy — drugs that treat ATTR-CM differently. Another 24% started stabilizers during the trial. That made it very hard to isolate what eplontersen was actually doing on its own.
The overall result disappointed. But one group stood out: patients who took no stabilizers at all. In that subset, eplontersen showed a hazard ratio of 0.71 for cardiovascular events. A hazard ratio below 1.0 signals benefit. Analysts noted this suggests the drug may work — just not when mixed with competing treatments.
Safety Was Fine — The Study Design Was the Problem
Ionis stressed that eplontersen was well tolerated. The safety profile matched prior results. So the failure was not about the drug hurting patients. Instead, the debate centers on how the trial was designed and who was enrolled.
Several analysts backed that view. Needham kept a Buy rating on Ionis but cut its price target from $105 to $86, according to GuruFocus. Jefferies also maintained a Buy, lowering its target to $90, according to Benzinga. Both firms argued the results reflect trial design issues, not a broken platform.
Stock Targets Slashed, But Bulls Hold Their Ground
The average 12-month price target across 21 analysts dropped from $103.57 to $102.62 in one round of cuts, then fell again to $97.43 from $99.38 in a follow-up revision, according to TradingView. Even at the lower target, analysts see roughly 15% upside from current levels.
Stifel moved to a Hold on Ionis while keeping Alnylam at Buy. That shift shows how Wall Street is now splitting the ATTR-CM field into winners and losers. Alnylam's drug competes directly with eplontersen, and investors saw the Ionis stumble as a gift to its rival.
ESC Congress 2026 Is the Next Big Test for Ionis
The story is not over. Ionis and AstraZeneca plan to present the full CARDIO-TTRansform data at the ESC Congress 2026. Analysts expect deeper subgroup data, biomarker trends, and secondary endpoints to give a clearer picture of where eplontersen stands.
Investors are watching closely. If the data show consistent benefit in patients not on stabilizers, Ionis could argue for a narrower but real market. For now, the stock trades at a steep discount, and the next conference is the company's best chance to change the narrative.
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