Novartis' Heart Drug Fails Major Clinical Trial, Threatening $900 Million Partnership
On November 7, Novartis, a massive pharmaceutical company, released its phase 3 clinical trial results for pelacarsen, an experimental cardiovascular drug. Headlining the outcome was its failure to prevent serious cardiovascular events, even though it reduced a major cholesterol-related risk marker by nearly 78%. This setback doesn’t just affect Novartis, but raises concerns about all emerging therapies for heart disease and their commercial potential. Additionally, the failure threatens future payments of a deal worth up to $900 million.
Pelacarsen targets lipoprotein(a), or Lp(a), which is a cholesterol-carrying particle that is found in patients struggling with heart attacks and strokes. The drug functions by stopping the formation of Lp(a) by interfering with a major protein involved in its production. This is accomplished with the use of oligonucleotide technology. Approximately 1 in 5 people have elevated Lp(a), which is why pelacarsen and other related treatments have such a potentially lucrative market.
In Novartis’ Lp(a)HORIZON trial, involving over 8300 patients, pelacarsen was found to reduce Lp(a) by around 78%. However, 12.3% of patients receiving pelacarsen experienced a major cardiovascular event, while 12.% of patients who received a placebo experienced a major cardiovascular event, a difference that was not statistically significant. What this means is that lowering Lp(a) does not translate into improved clinical outcomes.
As said before, the financial consequences extend beyond Novartis. In 2017, Novartis partnered with Ionis Pharmaceuticals to create and develop pelacarsen. The agreed-upon deal was worth up to $900 million, with $75 million paid upfront and $150 million in licensing fees. Now, nearing the end of 2026, marking a decade since the deal was made, Ionis has received more than $275 million through the partnership. However, this recent failure puts hundreds of millions in potential regulatory and sales milestone payments at risk.
Furthermore, the setback also creates doubt for companies like Amgen and Eli Lilly, which are both respectively developing their own therapies to target Lp(a). All three companies are looking to enter the highly lucrative market sitting behind cardiovascular failure, but if lowering Lp(a) does not provide any clinical benefit to heart failure-related events, they may have to rethink their strategy and whether lowering important biomarkers will translate into any real effects.
For Novartis and Ionis, the failure highlights the financial risks of investing heavily in late-stage drug development. While pelacarsen successfully achieved its intended biological effect, its inability to improve cardiovascular outcomes threatens the commercial opportunity that originally justified the investment.
