Double Phase III Trial Failures for Pelacarsen and Del-Desiran Wipe Out Over $40B in Novartis Market Value
In early September 2026, Novartis suffered back-to-back late-stage clinical failures that dealt a severe blow to its late-stage pipeline, wiping out more than $40 billion in the company's market capitalization.
Pelacarsen Fails Phase III Lp(a)HORIZON Trial (September 4, 2026)
On September 4, 2026, Novartis announced that its high-stakes antisense therapy pelacarsen (co-developed with Ionis Pharmaceuticals) failed to meet its primary endpoint in the Phase III Lp(a)HORIZON cardiovascular outcomes trial. The massive study enrolled 8,323 patients with elevated lipoprotein(a) [Lp(a)] and established cardiovascular disease (CVD). While pelacarsen successfully lowered Lp(a) levels by up to 80% (consistent with phase II results), it did not translate into a statistically significant reduction in major adverse cardiovascular events (MACE)1, which was measured as a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent coronary revascularization requiring hospitalization.
This failure has profound industry-wide implications, as it casts a shadow over the entire "Lp(a) hypothesis" and raises the burden of proof for rival Lp(a)-lowering clinical assets, including Amgen's olpasiran (OCEAN(a) trial, expected readout in 2028) and Eli Lilly's lepodisiran (ACCLAIM-Lp(a) trial, expected readout in 2029).
Del-Desiran Fails Phase III HARBOR Trial in DM1 (September 8, 2026)
Just days later, on September 8, 2026, Novartis announced another major pipeline setback: its investigational antibody-oligonucleotide conjugate (AOC) del-desiran (delpacibart etedesiran) failed to meet its primary endpoint in the Phase III HARBOR study. The trial evaluated del-desiran in approximately 150 patients with myotonic dystrophy type 1 (DM1), a progressive and debilitating genetic neuromuscular disease with no currently approved treatment options.
Del-desiran, which was the centerpiece of Novartis's $12 billion acquisition of Avidity Biosciences, failed to show a statistically significant improvement compared to placebo on the primary endpoint of video hand opening time (vHOT), a novel measure of hand myotonia. Though secondary endpoints showed some evidence of clinical activity, the clinical and commercial outlook of this multi-billion-dollar asset is severely damaged.
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An instance of Clearing a disease's signature biological biomarker does not guarantee functional clinical improvement. — Although pelacarsen successfully achieved its biological biomarker targets by dramatically reducing Lp(a), it failed to deliver any real-world cardiovascular outcomes. ↩︎