Olpasiran

iStock, Afry Harvy Novartis’ shares fell 13% this week after the report of three separate late-stage asset failures. The impact went beyond the Swiss drugmaker, dragging peers down across the market. Novartis is the sixth largest pharmaceutical company by market cap with a valuation of $212.2 billion, so it takes a lot to knock down an entity like that. But the failures of three different late-stage assets did a number on the Swiss drugmaker’s shares this week. First up, the antibody-oligonucleotide conjugate del-desiran failed a Phase 3 trial in myotonic dystrophy type 1. The therapy failed to improve hand opening time in the 160 enrolled patients. This was a blow for the drug—and patients with the rare genetic disorder—but also for Novartis’ $12 billion acquisition of Avidity Biosciences that provided the asset last year. Then, the antisense therapy pelacarsen did not show a significant benefit on cardiovascular risk in patients during a late-stage trial. The drug did lower levels of lipoprotein(a); however, the cardiovascular risk was the main goal of the test, indicating a failure. Finally, Novartis paused a clutch of Phase 2 trials for the CAR T cell therapy rapcabtagene autoleucel after three patient deaths. Novartis’ shares have fallen more than 13% this week in response to the failures and trial pauseswhich call into question the pharma’s entire growth pipeline. Novartis’ problems have caused a ripple across the pharma sector, according to analysts at Dow Jones . Amgen, which is the eighth largest pharma by market cap, fell sharply this week as well, since the company’s olpasiran is being tested in the same disease space as pelacarsen. Amgen’s asset, however, is an siRNA therapy. Eli Lilly, worth an eye-watering trillion dollars, is also in the lipoprotein(a)-lowering game with the siRNA therapy lepodisiran, and is also down slightly this week.

iStock, RomoloTavani The failure of Novartis’ pelacarsen to translate its Lp(a)-lowering effects to clinical benefits “marks a meaningful setback” for other companies taking a similar approach to cardiovascular risk, analysts say—including Eli Lilly and Amgen. Despite successfully lowering lipoprotein(a) levels in earlier studies, Novartis’ antisense therapy pelacarsen showed no significant benefit on cardiovascular risk in a late-stage study. This outcome, analysts said, raises questions about a popular target for heart disease. “A large focus across the biotech industry has been paid to lowering Lp(a) levels,” analysts at William Blair told investors in a note on Sept. 4. Eli Lilly and Amgen, for example, are also exploring this approach. Novartis is also at the forefront of this effort, with pelacarsen eliciting an up to 80% reduction in the levels of Lp(a) versus placebo in a mid-stage study. The Phase 3 Lp(a)HORIZON study was meant to examine whether these biomarker benefits would translate to clinical improvements. The pharma is advancing pelacarsen in collaboration with Ionis Pharmaceuticals under an August 2023 agreement . In a readout on Friday, Novartis announced that pelacarsen failed its primary endpoint of lowering the risk of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and urgent coronary revascularization needing hospitalization, as compared with placebo. The pharma did not provide specific data to elucidate the magnitude of pelacarsen’s effect, but promised to do so at a future medical congress. This outcome “marks a meaningful setback for dedicated Lp(a)-lowering therapies,” BMO Capital Markets wrote in an investor note on Friday. While the firm concedes that certain study design differences prevent the complete invalidation of Lp(a) as a therapeutic target, Novartis’ failure “raises the burden of proof for Lilly’s lepodisiran and Amgen’s olpasiran”—both investigational assets that, like pelacarsen, have previously shown Lp(a)-lowering effects and which are currently in late-stage trials assessing clinical outcomes. Both olpasiran and lepodisiran are siRNA therapies that lower Lp(a) expression. Lilly in March last year touted a nearly 94% reduction of the biomarker, while Amgen in late 2022 showed reductions that reached more than 97% . Lepodisiran is currently in the Phase 3 ACCLAIM-Lp(a) trial , with initial data expected in 2029, while olpasiran’s OCEAN(a) study is slated for a topline readout in 2028. “We do see meaningful risk to a potential future in Lp(a)-driven CVD trials in light of results from Lp(a) HORIZON,” William Blair said. Still, there remains room to be hopeful, particularly for Amgen, Truist Securities told investors on Monday. For olpasiran, the gamble now “shifts to a higher-risk/higher-reward rather than becoming outright impaired,” the analysts noted, pointing to “important differences” between Amgen’s and Novartis’ programs. These include the “deeper” Lp(a) reduction of olpasiran and OCEAN(a)’s enrollment of a more high-risk population. Aside from Amgen and Lilly, Merck last year bet nearly $2 billion in biobucks to partner with China’s Jiangsu Hengrui to advance an Lp(a) inhibitor called HRS-5346. Cardiovascular Merck, Amgen double down on bad cholesterol to vanquish number 1 killer New guidelines from two leading medical associations suggest that efforts to reduce bad cholesterol should focus on maintaining low levels of two key lipoproteins. Big pharma is all in, looking to improve on the standard statins to help vanquish America’s number one killer: heart disease. May 11, 2026 · 6 min read · Ben Hargreaves Read more