Novartis hit as Lp(a) drug fails cardio outcomes trial
Victoria
Novartis shares dipped lower this morning after the company revealed its Lp(a)-targeted drug, pelacarsen, failed to reduce cardiovascular risks in a major phase 3 trial.
In the keenly anticipated Lp(a)HORIZON study, pelacarsen given as a once-monthly subcutaneous injection did not meet its primary objective of reducing the risk of cardiovascular events – cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent coronary revascularisation requiring hospitalisation – compared to placebo.
Novartis share price was trading down 3% at the time of writing, as investors expressed their disappointment that Ionis-partnered pelacarsen may not be the blockbuster cardiovascular drug that the two companies were hoping for.
Like LDL-cholesterol, elevated Lp(a) is recognised as an independent genetic risk factor for coronary artery disease, heart attack, stroke, peripheral arterial disease, and aortic stenosis, potentially involved in around half of all cases.
However, unlike LDL-cholesterol, there are currently no approved drugs that can reduce levels of Lp(a) in the body. As pelacarsen was effective in reducing Lp(a) levels in Lp(a)HORIZON, the result has raised fears that the failure to move the needle on cardiovascular outcomes may extend to other drugs in the class, such as Amgen's olpasiran and Eli Lilly's lepodisiran, which are also in phase 3 testing.
Shares in both Amgen and Lilly were also trading lower following Novartis' announcement, along with Ionis, whose shares lost 10% of their value.
Novartis' chief medical officer said that Lp(a)HORIZON study – which enrolled more than 8,000 participants – was "pioneering" and "designed to answer one of the most important unanswered questions in cardiovascular medicine." Lp(a) is elevated in around 20% of people worldwide.
He added: "These are not the results we hoped for, but they provide important evidence that advances scientific understanding of the relationship between Lp(a) lowering and cardiovascular outcomes and may help inform future approaches to cardiovascular risk management."
Results from the trial will be reported at an upcoming medical congress, according to the drugmaker, and cardiologists will be looking at the data closely to gauge its significance to the broader Lp(a) class.
Novartis licensed pelacarsen from Ionis in 2019 for $150 million upfront, with another $650 million in potential development, regulatory, and sales milestone payments.
The setback is a big disappointment for Novartis, which needs its pipeline to deliver new products as it faces a steep patent cliff caused by the loss of market exclusivity for cardiovascular blockbuster Entresto (sacubitril and valsartan), which reached a peak of almost $8 billion in 2024 and came in at under $2.5 billion in the first half of this year.
The company is expecting patent expiries to lead to around $4 billion in lost revenue this year, as generic and biosimilar competition bites into other brands like platelet booster Promacta/Revolade (eltrombopag), cancer drug Tasigna (nilotinib), and Xolair (omalizumab) for allergies and asthma.
Other big sellers – blood cancer therapy Jakavi (ruxolitinib) and immunology blockbuster Cosentyx (secukinumab) – are also due to lose market exclusivity in the next few years.
Pelacarsen's failure places more pressure on other experimental therapies at Novartis, including oral BTK inhibitor remibrutinib for multiple sclerosis and other indications and gene therapies like delpacibart etedesiran (del-desiran) for Duchenne muscular dystrophy (DMD), to plug the revenue shortfall.
