Cardiovascular Trial Setbacks
Ionis Shares Fall After Two Partnered Cardiovascular Trials Miss Key Goals
Anonymous
Key Points
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The Lp(a)HORIZON trial enrolled more than 8,300 high-risk patients and followed them for six years. Its composite endpoint included cardiovascular death, heart attack, stroke and urgent coronary revascularization; pelacarsen lowered Lp(a) but failed to produce a statistically significant improvement in that endpoint.
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Pelacarsen’s result has implications beyond Ionis and Novartis because it challenges the broader assumption that lowering Lp(a) will translate into lower cardiovascular risk. Amgen and Eli Lilly are also developing therapies aimed at the same target, making the detailed pelacarsen data relevant to the wider drug class.
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Ionis shares fell as much as 13.1% to $50.51 in premarket trading after investors assessed the pelacarsen result; another report said the stock was down about 10% in premarket trading.
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Despite the setbacks, analyst coverage remained broadly favorable: MarketBeat data cited 17 Buy ratings, four Holds and one Sell, producing a consensus rating of “Moderate Buy” and an average price target of $92.95.
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Ionis director Michael Hayden bought 15,000 shares at an average price of $53.38, a transaction valued at $800,700; following the purchase, his direct holdings increased to 19,000 shares.
Ionis Pharmaceuticals shares fell as much as 13% after a major cardiovascular drug trial failed to meet its main goal. TipRanks reported the stock dropped to $50.51 in premarket trading following disappointing Phase 3 results for pelacarsen, a therapy developed with partner Novartis. The drug lowered lipoprotein(a) levels but did not significantly reduce heart attacks, strokes, or other major cardiovascular events in the Lp(a)HORIZON trial.
Analysts quickly cut their price targets in response. TipRanks noted that HC Wainwright lowered its target to $100 from $115, while Raymond James reduced its target to $84 from $87. Despite the cuts, most analysts kept Buy ratings, citing Ionis's broader pipeline as a reason for optimism. The consensus price target remained at $92.95, suggesting analysts still see upside from current levels.
Pelacarsen Fails Despite Lowering Lipoprotein(a)
The Lp(a)HORIZON trial followed more than 8,300 high-risk patients for six years. DefenseWorld reported that pelacarsen successfully lowered lipoprotein(a) but failed to produce a statistically significant improvement in the trial's main endpoint — a combination of cardiovascular death, heart attack, stroke, and urgent coronary revascularization. This disconnect challenges a core assumption in the drug development field: that lowering lipoprotein(a) automatically reduces cardiovascular risk.
The setback has ripple effects across the industry. Amgen and Eli Lilly are also developing therapies targeting lipoprotein(a), making pelacarsen's detailed results relevant to their programs. Investing.com noted that HC Wainwright removed pelacarsen from its valuation model entirely due to the failure. The drug's loss could reduce Ionis's projected royalties and milestone payments, which had been estimated at mid-teens to low-20% royalties plus as much as $650 million in milestones.
A Separate AstraZeneca Program Also Disappoints
Pelacarsen was not Ionis's only cardiovascular setback. DefenseWorld reported that eplontersen, developed with partner AstraZeneca, also failed in the CARDIO-TTRansform Phase 3 trial. This double miss raised questions about Ionis's cardiovascular programs and weighed on investor confidence. The failures underscored that even well-designed trials can produce unexpected negative results.
The cumulative effect of two failed trials accelerated analyst downgrades. TipRanks cited that multiple firms cut price targets, with ranges from the mid-$50s to $90. Despite the negative news, the analyst community remained cautious optimists — 17 Buy ratings, four Holds, and one Sell kept the consensus at "Moderate Buy." Many analysts pointed to Ionis's approved drug Tryngolza and the ongoing REVEAL study of obudanersen as potential sources of future value.
Insider Buying Signals Confidence Despite Stock Decline
Not all voices at Ionis reflected pessimism. Investing.com reported that company director Michael Hayden purchased 15,000 shares at an average price of $53.38, investing approximately $800,700. After the transaction, Hayden's direct shareholdings rose to 19,000 shares. Insider buying during a sharp stock decline is often viewed as a bullish signal that company leaders believe the market has overreacted.
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