A Failed Cholesterol Drug Raises the Stakes for Amgen (AMGN) and Eli Lilly (LLY) Too

A Failed Cholesterol Drug Raises the Stakes for Amgen (AMGN) and Eli Lilly (LLY) Too

Fatima Gulzar

Fri, September 18, 2026 at 2:57 AM GMT+3 4 min read

On September 8, 2026, CNBC reported that Novartis' failed pelacarsen trial has raised the stakes for rival experimental cholesterol drugs from Amgen Inc. (NASDAQ:AMGN) and Eli Lilly and Company (NYSE:LLY), both of which are racing to prove that lowering lipoprotein(a), or Lp(a). It can meaningfully reduce heart attacks and strokes.

Analysts said Amgen's olpasiran faces the clearest negative read-through given its similar trial design. Lilly's lepodisiran is being tested in a broader patient population that could limit how directly Novartis' failure applies. It is also described as less material to Lilly's overall valuation than pelacarsen was for Novartis.

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Bull Case

Amgen Inc. (NASDAQ:AMGN) and Eli Lilly and Company (NYSE:LLY) could still succeed where Novartis failed. Pelacarsen's failure does not establish that lowering Lp(a) cannot reduce cardiovascular events. Analysts noted that Novartis' trial faced a high statistical hurdle and that Amgen's olpasiran and Lilly's lepodisiran have produced stronger Lp(a) reductions in earlier studies. Both companies also continue testing their drugs in specific patient populations with high Lp(a). It leaves room for their trials to produce different outcomes from Novartis' study.

Lilly's lepodisiran faces a less direct read-through than Amgen's olpasiran. Analysts view Amgen's olpasiran as the closest comparison to pelacarsen because the programs use similar trial designs. Lilly's lepodisiran is being tested in an overall patient population. It could make Novartis' failure less directly applicable. Analysts also view lepodisiran as less material to Lilly's overall valuation than pelacarsen was to Novartis. It reduces the potential financial impact of an unsuccessful outcome.

Both companies can absorb an Lp(a) setback better than a company that depends heavily on a single experimental drug. Amgen and Lilly each make substantial revenue from established medicines. It gives them financial resources to continue funding their pipelines even if their Lp(a) programs disappoint. For Lilly in particular, the firm's rapidly growing obesity franchise represents a much larger component of its investment story. It means lepodisiran does not carry the same company-level importance that pelacarsen carried for Novartis.

Bear Case

Amgen Inc. (NASDAQ:AMGN) faces the clearest negative read-through from Novartis' failure. Analysts identified olpasiran as the rival program most directly exposed because its trial design closely resembles pelacarsen's. If the underlying difficulty involves more than Novartis' specific drug or trial execution, Amgen could face a similar challenge in showing that lower Lp(a) actually turns into fewer heart attacks and strokes.

The failure raises the scientific and regulatory burden for the entire Lp(a) drug class. Novartis' trial failed to show that pelacarsen reduced cardiovascular events despite targeting patients with elevated Lp(a). That result gives regulators, physicians and investors more reason to scrutinize whether Lp(a) reduction alone produces real clinical benefits. So Amgen and Lilly may need especially strong event-reduction data to establish their drugs as commercially important cardiovascular treatments.

Both companies still face binary clinical risk before they can turn Lp(a) into real revenue. Neither olpasiran nor lepodisiran has yet delivered the definitive late-stage cardiovascular-outcome evidence investors need. A disappointing result could force analysts to reduce peak-sales expectations and weaken the investment case for the programs, while a successful outcome could materially solidify each company's pipeline. So Novartis' failure has made the upcoming readouts more important for both Amgen and Eli Lilly and Company (NYSE:LLY).

Hedge Fund Sentiment

Amgen Inc. (NASDAQ:AMGN)'s hedge fund position value nearly doubled to $3.14 billion in the second quarter from $1.63 billion in the first, with holder count roughly steady at 66 versus 65, according to Insider Monkey's database. Eli Lilly and Company (NYSE:LLY)'s hedge fund following grew even more sharply over the same period, with holders rising to 152 from 132 and position value jumping to $17.24 billion from $12.58 billion.

Conclusion

Novartis' failed pelacarsen trial raises the risk for Amgen and Eli Lilly and Company (NYSE:LLY) as investors now demand stronger evidence that lowering Lp(a) can reduce cardiovascular events. Amgen faces the more direct read-through because olpasiran closely resembles pelacarsen's program. Lilly has greater protection because lepodisiran represents a smaller part of its overall valuation and the company has a stronger growth engine elsewhere.

Both companies still have an opportunity to prove the Lp(a) drug class can deliver clinical and commercial benefits. But their upcoming trial results could have a significant impact on pipeline valuations and long-term growth expectations.

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