Heart failure drug shows big promise

08/30/2014 9:33 PM

09/01/2014 9:11 AM

A new study reports one of the biggest potential advances against heart failure in more than a decade: a first-of-its-kind experimental drug that lowered the chances of death or hospitalization by about 20 percent.

Doctors say the Novartis drug — which doesn’t have a name yet — seems like one of those rare breakthrough therapies that could quickly change care for more than half the 6 million Americans and 24 million people worldwide with heart failure.

“This is a new day” for patients, said Dr. Clyde Yancy, cardiology chief at Northwestern University in Chicago and a former president of the American Heart Association.

“It’s been at least a decade since we’ve had a breakthrough of this magnitude,” said Yancy, who had no role in the study.

It involved nearly 8,500 people in 47 countries and was the largest experiment ever done in heart failure. It was paid for, designed and partly run by Novartis, based in Basel, Switzerland. Independent monitors stopped the study in April, seven months earlier than planned, when it was clear that the drug was better than an older one that is standard now.

During the 27-month study, the Novartis drug cut the chances of dying of heart-related causes by 20 percent and for any reason by 16 percent, compared with the older drug. It also reduced the risk of being hospitalized for heart failure by 21 percent.

“I think that when physicians see these data, they will find it compelling and what we will see is a paradigm shift,” said Dr. Milton Packer, a professor of clinical sciences at the University of Texas Southwestern Medical Center at Dallas and one of two principal investigators in the study.

“We are really excited,” Packer said. The benefit “exceeded our original expectations.”

A leading killer

The results were disclosed Saturday at a European Society of Cardiology conference in Barcelona and published online by The New England Journal of Medicine.

Novartis will seek approval for the drug — for now called LCZ696 — by the end of this year in the United States and early next year in Europe. That means the drug could get to patients as early as next year.

Heart failure is the top reason that older people are hospitalized and a leading cause of death. It develops when the heart muscle weakens over time and can no longer pump effectively, often because of damage from a heart attack. Fluid can back up into the lungs and leave people gasping for breath.

The people in this study were already taking three to five medicines to control the condition. One medicine often used is an ACE inhibitor, and the study tested one of these — enalapril, sold as Vasotec and in generic form — against the Novartis drug.

The new drug is a twice-daily combination of two medicines that block the effects of substances that harm the heart while also preserving ones that protect it. One of the medicines also dilates blood vessels and allows the heart to pump more effectively.

In the study, 26.5 percent on the older drug, enalapril, died of heart-related causes or were hospitalized for heart failure, versus less than 22 percent of those on the Novartis drug. Quality of life was also better with the experimental drug.

“We now have a way of stabilizing and managing their disease which is better than what we could offer them before,” Packer said.

‘Favorable number’

The new drug also seemed safe — reassuring because safety concerns doomed a couple of other promising-looking treatments over the last decade.

The Novartis drug saw more cases of low blood pressure and nonserious swelling beneath the skin. But the older drug brought more kidney problems, excess potassium in the blood and coughing. More people on the older treatment dropped out of the study than those on the new one.

About 32 people would need to be treated with the new drug to prevent one death from heart-related causes.

“That’s a favorable number,” said Dr. Joseph G. Rogers, a Duke University cardiologist with no role in the study. He said the benefits were big enough that “I would switch people over” as soon as the drug is available.

The drug “may well represent a new threshold of hope” for patients, Dr. Mariell Jessup, heart failure chief at the University of Pennsylvania, wrote in a commentary in the journal. It may help “a wide spectrum of patients, even those who are currently receiving the best possible therapy.”

Yancy said: “The results are not just positive — they are remarkably positive and positive in every dimension. Patients with heart failure are eager, if not desperate, to have better options.”

Potential blockbuster

Novartis announced in March that the study was ending early because the drug had been better than the comparison drug. But until Saturday, it was not known how much better.

Some Wall Street analysts predict that the drug will achieve billions of dollars in annual sales. Seamus Fernandez, an analyst at Leerink Partners, said Saturday that the results are “near best-case” and “could result in faster uptake, higher penetration and more robust branded pricing.”

As a proprietary drug, LCZ696 is likely to be expensive. Tim Anderson, an analyst at Sanford C. Bernstein & Co., estimates that it might cost $7 a day in the United States, or about $2,500 a year. Existing drugs are generic, costing as little as $4 a month, so insurers might balk at paying for the new drug.

Dr. Marc A. Pfeffer, a cardiologist at Brigham & Women’s Hospital who was not involved in the trial, said it was impressive that LCZ696 could improve on existing therapy “because the bar really is high.”

But Dr. Alfred Bove, a professor emeritus at Temple University, said that although the relative risk reduction is large, the absolute difference is only about 3 percentage points — 17 percent of patients getting LCZ696 died of any cause compared with 19.8 percent in the control arm.

Yancy, of Northwestern, said one caution was that only about 5 percent of patients in the study were of African descent. In the U.S., blacks suffer disproportionately from heart failure.

About a decade ago, he said, a somewhat similar drug never made it to the market because it caused a serious side effect called angioedema, mainly in African-Americans. He said, however, that LCZ696 does not seem to pose that risk, though more observation is needed.

LCZ696 is a combination of two drugs. One is valsartan, the blockbuster heart drug that Novartis sells as Diovan. The other component inhibits the enzyme neprilysin, a new mechanism for a heart failure drug.

Novartis could use a hit to make up for declining sales of Diovan, which has lost patent protection. A success with LCZ696, which is for chronic heart failure, would help offset the company’s recent inability to win regulatory approval for serelaxin, for acute heart failure.

This report includes material from The New York Times.

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