Novartis Shares Fall as Key Heart Drug Misses Target in Late-Stage Trial

 Novartis Shares Fall as Key Heart Drug Misses Target in Late-Stage Trial

**Shares of Novartis dropped 3.2% in European trading Monday after its closely watched heart drug, pelacarsen, failed to reduce cardiovascular events in a pivotal late-stage study — a major setback for the Swiss drugmaker's efforts to offset patent losses and revive its pipeline.**

## The Trial That Disappointed

The results were clear and disappointing. Novartis and its partner Ionis Pharmaceuticals announced on September 4 that pelacarsen, an experimental drug designed to lower high levels of lipoprotein(a) — a cholesterol-carrying particle linked to higher heart risk — did not meet its primary goal in the Phase III Lp(a)HORIZON trial .

The drug did not reduce the risk of major adverse cardiovascular events, including death from heart disease, heart attack, stroke, or the need for urgent procedures to restore blood flow to the heart . The trial enrolled more than 8,300 patients with elevated Lp(a) levels and established cardiovascular disease .

The failure was particularly notable because pelacarsen had successfully lowered Lp(a) levels — consistent with previous studies — but that reduction simply did not translate into fewer cardiovascular events .

"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," said Novartis Chief Medical Officer Shreeram Aradhye .

## Market Reaction: A Sell-Off Across the Sector

The market response was swift and punishing:

- **Novartis** shares fell 3.2% in European morning trading Monday, extending an after-hours drop of about 5% in the U.S. 

- **Ionis Pharmaceuticals** shares lost approximately 10-12% in after-hours trading following the news 

- **Amgen**, which is developing a similar Lp(a)-lowering drug called olpasiran, saw its shares fall nearly 7% in after-hours trading 

Despite the drop, Novartis shares remain up roughly 14% year-to-date, reflecting investor confidence in other parts of the company's pipeline .

## A Blow to Novartis's Pipeline Strategy

The failure of pelacarsen is a significant setback for Novartis as it navigates one of the steepest patent cliffs in its history. Entresto, the company's former top-selling heart drug, saw sales fall 50% in the second quarter due to generic competition in the United States .

Novartis had positioned pelacarsen, along with multiple sclerosis drug remibrutinib and genetic therapy del-desiran, as key drivers of long-term growth . Together, these three experimental drugs represented more than $10 billion in potential peak annual sales .

## Silver Linings: Remibrutinib Success

There was some good news for Novartis last week. The company's multiple sclerosis drug remibrutinib succeeded in two late-stage studies, with analysts estimating it alone could bring in up to $9 billion in peak annual sales .

The REMODEL-1 and REMODEL-2 studies met their primary endpoint, significantly reducing annualized relapse rates versus Aubagio in the target patient population .

## What This Means for Investors

**The Lp(a) Hypothesis Remains Unsettled**

The failure of pelacarsen does not necessarily mean the Lp(a) mechanism is dead. Citi analyst Geoffrey Meacham noted that full trial data are needed to determine whether the miss reflects the drug's mechanism of action, trial design, or broader doubts about Lp(a) reduction .

"However, I would not declare the mechanism dead," Meacham said . The first dedicated outcomes failure "lowers confidence across the class and places greater pressure on later studies to demonstrate that deeper lowering of Lp(a) can produce a clinically meaningful reduction of major cardiovascular events" .

**Clinical Trial Risk Is Real**

The pelacarsen failure and the recent decision to temporarily halt trials of an experimental cell therapy for autoimmune diseases after three patient deaths underscore the inherent risks in drug development — even for companies with strong track records .

**Competitor Impact**

Amgen and Eli Lilly are both developing their own Lp(a)-lowering drugs, though they're further behind in development . The Novartis failure clouds the outlook for these programs, even if the mechanism itself is not entirely discredited.

## Frequently Asked Questions (FAQs)

### 1. What was pelacarsen and what was it supposed to do?

Pelacarsen was an experimental drug designed to lower lipoprotein(a), a genetic risk factor for cardiovascular disease that affects roughly one in five people worldwide. The drug was given as a once-monthly subcutaneous injection .

### 2. What happened in the trial?

The Phase III Lp(a)HORIZON trial failed to meet its primary endpoint. While pelacarsen did successfully lower Lp(a) levels, this reduction did not translate into fewer cardiovascular deaths, heart attacks, or strokes compared with placebo .

### 3. How much did Novartis shares fall?

Novartis shares fell 3.2% in European trading Monday following the news. The stock had previously dropped about 5% in after-hours trading on September 4 .

### 4. Why is this a big deal for Novartis?

Novartis is facing significant patent expirations, particularly for its former top-selling heart drug Entresto, which saw sales drop 50% in Q2 2026. The company needs new growth drivers to offset these losses .

### 5. Does this mean Lp(a)-lowering drugs are dead?

Not necessarily. Experts, including Citi analyst Geoff Meacham, caution against declaring the mechanism dead without full trial data. However, the failure does reduce confidence across the class .

### 6. What about other Novartis pipeline drugs?

Novartis recently reported positive results for remibrutinib in multiple sclerosis, a success that helped offset some of the disappointment from the pelacarsen failure .

## The Bottom Line

The failure of pelacarsen is a genuine setback for Novartis, removing a potential blockbuster from its pipeline at a critical moment. The company is navigating major patent expirations and needs new drugs to maintain growth.

However, the recent success of remibrutinib in multiple sclerosis offers some reassurance that Novartis's pipeline can still deliver. Investors will now look to the company's remaining pipeline candidates, particularly in rare diseases, as the next potential catalysts .

The Lp(a) hypothesis itself remains unsettled. While this trial was a bellwether for the drug industry, experts caution against declaring the mechanism dead until full data are analyzed. Amgen and Eli Lilly's similar programs are now under closer scrutiny .

For now, the market has delivered its verdict. But as Novartis's Chief Medical Officer Shreeram Aradhye noted, these results "provide important evidence that advances scientific understanding" — even if they weren't the outcome anyone hoped for .

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## Disclaimer

*This article is for informational and educational purposes only and does not constitute financial, investment, tax, or legal advice. All views expressed are based on publicly available information as of September 7, 2026. Clinical trial results, stock prices, and market conditions are subject to change. Past performance is not indicative of future results. Before making any financial or investment decisions based on the content of this article, please consult with qualified professionals who can evaluate your specific situation.*