Dive Brief:

• A Novo Nordisk heart drug missed the main goal of a Phase 3 trial, failing to show it prevented heart attacks, strokes or cardiovascular death in people with hardened arteries or chronic kidney disease, the company said Friday.
• Called ziltivekimab, the drug is part of a sprawling clinical program involving three late-stage trials that have collectively enrolled more than 20,000 people. Two others, in people with heart failure or who’ve had an acute heart attack, are ongoing. Results are expected next year. They all aim to show lowering levels of an inflammatory protein called IL-6 can can reduce the risk of heart-related complications and death.
• Novo gained control of ziltivekimab through a 2020 acquisition of Corvidia Therapeutics, for which it paid $725 million up front and promised up to $2.1 billion in total payouts. Novo said it will take a “non-cash impairment charge” in the third quarter but will not need to change its operating profit forecasts. Its shares fell as much as 10% Friday.

Dive Insight:

Novo has already acknowledged ziltivekimab is a bit of a gamble. In the company’s most recent earnings call, science chief Martin Holst Lange described the drug as having “very high potential across those three indications, but also high risk.”

The trial results Novo reported Friday bore out that assessment. Called Zeus, the study enrolled more than 6,000 people with chronic kidney disease or atherosclerotic coronary artery disease, which was characterized as previously having a heart attack or major blockages in their blood vessels. 

Enrollees also had to have elevated levels of a key inflammatory protein known as “high-sensitivity C-reactive protein,” or hsCRP. The hypothesis Novo has been testing is that blocking IL-6 will reduce levels of this protein and, in turn, protect heart health.

Study recruits were randomized into two equal-sized groups receiving either ziltivekimab or a placebo. They were followed for up to four years.

What Novo found was that the drug worked as intended, measurably lowering IL-6 as well as hsCRP. But that impact didn’t lead to a heart benefit, raising questions about the approach.

Novo also said the overall rates of adverse events, including those graded as “serious,” were similar in both study groups. A higher proportion of people who received ziltivekimab had serious infections — a known risk of drugs that target IL-6 — but that didn’t lead to a difference in the number of deaths among drug recipients. 

“The study provides important scientific evidence that will inform our ongoing cardiovascular research and the development of treatments for patients who continue to face substantial unmet need,” Lange said in a statement.

The findings rippled across the biotech sector, too, as investors saw the results as potentially troublesome for other drugmakers aiming to reduce cardiovascular risk by lowering levels of hsCRP. Shares of BioAge Labs, Neurocrine Biosciences and Neumora Therapeutics — all of which are working on drugs that use a different mechanism to drop hsCRP — fell in morning trading. BioAge was impacted the most, with share tumbling as much as 65%.

The “lack of signal,” as well as appearance of serious infections, “challenge the role” of hsCRP in protecting the heart, wrote William Blair analyst Andy Hsieh.