Novartis heart drug trial miss hits shares

Novartis (NVS) announced that its experimental cardiovascular drug pelacarsen failed to meet the primary endpoint in the Phase 3 Lp(a)HORIZON outcomes trial. The study was designed to test whether lowering lipoprotein(a), or Lp(a), would translate into fewer major cardiovascular events in high-risk patients.

While pelacarsen substantially reduced Lp(a) levels in the trial population, this biomarker improvement did not lead to a reduction in the composite of major cardiovascular events when compared with placebo. As a result, the trial did not demonstrate a clinical benefit on its main predefined measure of success.

Lp(a)HORIZON was a Phase 3, randomized, placebo-controlled, double-blind, multi-center cardiovascular outcomes study. It enrolled about 8,323 patients who had both elevated Lp(a) and established cardiovascular disease, targeting a population considered at increased risk of heart-related events.

The primary endpoint was a four-point major adverse cardiovascular event composite, consisting of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and urgent coronary revascularization requiring hospitalization. Pelacarsen was evaluated against placebo to determine whether its Lp(a)-lowering effect would reduce the incidence of this composite endpoint.

Following the disclosure of the topline results, Novartis shares fell as much as 3.6% in early trading on Monday. The negative outcome for a late-stage cardiovascular asset added immediate pressure to investor sentiment around the company.

Ionis Pharmaceuticals (IONS), which partners with Novartis on pelacarsen, declined about 10% in extended trading after the announcement. Amgen (AMGN), which is developing a similar Lp(a)-targeting treatment, fell about 5% in extended or postmarket trading, reflecting broader market reassessment of this drug class.

Novartis stated that full topline results from Lp(a)HORIZON and additional analyses will be presented at an upcoming medical meeting. These data are expected to provide more detailed insight into the relationship between Lp(a) lowering and cardiovascular outcomes in the studied population.

The failure to achieve the primary endpoint increases attention on Novartis’s remaining late-stage pipeline, as well as on competing Lp(a)-lowering programs. Investors and industry observers are now focused on how the forthcoming detailed results may influence future approaches to cardiovascular risk management involving Lp(a).