Novartis (NVS) reported its third clinical failure in just seven days. Its late-stage clinical study evaluating pelacarsen failed to meet the primary endpoint, namely reducing the risk of cardiovascular events compared with placebo. This antisense oligonucleotide drug was originally discovered by Ionis Pharmaceuticals (IONS) and licensed to Novartis in 2019, with the aim of inhibiting the production of lipoprotein(a), or Lp(a). About 20% of people worldwide have elevated Lp(a) levels, and dietary or lifestyle changes usually do little to help. Novartis reported that pelacarsen did lower Lp(a) levels, but it did not achieve a statistically significant reduction in cardiovascular events. Analysts had previously estimated that if the drug succeeded, peak annual sales could reach $4 billion to $5 billion.
Amgen (AMGN) and Eli Lilly (LLY) are also developing drugs to lower Lp(a). After the Novartis news emerged, Amgen’s stock fell 10% and has not recovered since, while Eli Lilly’s stock fell only about 3%. This relatively mild impact is firstly because the pelacarsen results did not overturn the premise that lowering Lp(a) levels may improve cardiovascular outcomes, and the current data are not yet sufficient to draw such a conclusion. More importantly, Eli Lilly’s lepodisiran adopts a different approach from both Novartis and Amgen, achieving a greater reduction in Lp(a) than pelacarsen in a phase 2 trial, and its later-stage studies also included a broader patient population. Perhaps the biggest reason, however, lies in Eli Lilly’s dominant position in the diabetes and obesity market. In the second quarter of 2026 alone, Eli Lilly generated $23 billion in revenue, of which about $14.9 billion came from Mounjaro and Zepbound.
The failure of pelacarsen may indeed increase the risk that lepodisiran will also fail, and Novartis said the full trial data will be presented at an upcoming medical conference. But Eli Lilly has another opportunity to improve cardiovascular outcomes. Thanks to its 2025 acquisition of Verve Therapeutics, its pipeline includes the base-editing therapy VERVE-102, which edits DNA to turn off the PCSK9 gene in order to lower LDL cholesterol. In a phase 1 trial, a single intravenous infusion achieved dose-dependent reductions in PCSK9 and LDL cholesterol, and the effect was maintained over an 18-month follow-up period. For Eli Lilly, however, the most important story remains its diabetes and obesity business, and Novartis’s setback is hardly something that would change the game for this major pharmaceutical company.
Eli Lilly said on Monday that its oral weight-loss drug Foundayo has captured more than 30% of new patients in the U.S. oral obesity treatment market, narrowing the early lead that Novo Nordisk (NVO) had gained with its Wegovy oral tablet. Foundayo was launched in early April, about three months later than its competitor. Novo Nordisk CEO Mike Doustdar said in August that the Wegovy oral tablet still held about 90% of the U.S. oral weight-loss market. Investors are closely watching demand for oral weight-loss drugs, as such drugs are expected to expand the market by attracting patients unwilling to use injections. Novo Nordisk expects that by 2030, oral drugs will account for more than one-third of GLP-1 weight-loss treatment use, and analysts expect that by then the U.S. obesity treatment market alone will exceed $100 billion annually.
