Novartis drug study opens up new opportunities in fighting heart attacks and strokes – the washington post world j gastrointestinal oncol impact factor

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The findings, more than two decades after the discovery of powerful cholesterol-lowering drugs, called statins, taken by tens of millions, were announced Sunday at a medical conference in Barcelona and published in two leading medical journals.

“It’s a new paradigm: a new opportunity to further reduce death and disability,” said Mark Creager, a past president of the American Heart Association, who was not involved in the study. “We’ve made such tremendous inroads in treating heart disease over the last couple of decades, and it’s hard to imagine we could confer additional benefits, but here you go.”

But the implications and timing of any benefit for patients remain to be seen. The drug company that sponsored the trial, Novartis, plans to meet with regulators this fall and file for approval by the end of the year. The drug, an injection given once every three months, would then be reviewed by the Food and Drug Administration.

A key question is which patients will benefit; the study showed its effect — a 15 percent drop in a combined measure of heart attacks, stroke and cardiovascular death — in a select, high-risk population of people who had suffered a previous heart attack and had high levels of a marker of inflammation in their blood. But a subset of patients appeared to get greater benefit from the drug, called canakinumab.

About 15 million people in the United States suffer from the general type of heart disease studied in the trial, according to David Goff, director of the division of cardiovascular sciences at the National Heart, Lung and Blood Institute. There are about 635,000 first-time heart attacks a year in the United States. Of those who survive a heart attack, about 40 percent have high inflammation that puts them at risk for another, despite current therapies.

When cells are injured, they release signaling chemicals and attract immune cells to the site of injury. This process is typically protective, but in heart disease, an inflammation response can contribute to the growth and rupture of fatty deposits that block blood vessels — the ingredients for a heart attack.

“To me, this is like rolling back the clock on statins all the way back to 1994. The first statin came out and we said, ‘Wow, here’s a new class of drugs that can really impact on heart attack and stroke,’ " said Paul Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital in Boston who has doggedly pursued the “inflammatory hypothesis” of heart disease for more than two decades. Ridker has served as a paid consultant to Novartis. “This is the first step, but a big one that is very exciting.”

The trial results don’t mean targeting inflammation is a magic bullet or that people should give up trying to manage cholesterol. Canakinumab, which is already approved for rare diseases under the brand name Ilaris, came with a serious side effect — an increase in the risk of rare fatal infections. Despite the cardiovascular benefit — and a reduction in lung cancer mortality — there was no overall survival benefit, although cardiologists noted that the trends were in the right direction.

“I once described this trial at a meeting as being ‘courageous.’ … This was just a real long shot in many people’s eyes,” said Steven Nissen, a cardiologist at the Cleveland Clinic who was not involved in the study but acts as an unpaid adviser to Novartis.

“It opens up an entirely new vista for the treatment of heart disease, because now everybody on the planet — in the pharmaceutical industry and in research institutions like ours and at the National Institutes of Health — are going to be looking to find anti-inflammatory therapies.”

Such drugs typically carry high price tags because of the tiny number of patients they treat. Novartis executives said it was premature to discuss pricing. But under its current list price, a year’s therapy would cost $64,000. The cardiovascular benefit of the drug was similar to a recent class of cholesterol-lowering drugs that have faced slow adoption in the real world, due in large part to their high list prices of more than $14,000 a year.

“What would be truly a shame to me is if we travel down this same pathway, where there is an exciting development clinically — where patients can benefit — and there’s kind of a breakdown in the system from the pricing decisions of manufacturers and payers that just lead to gridlock and friction and clinicians have a hard time" prescribing it, said Steven Pearson, president of the Institute for Clinical and Economic Review, a nonprofit that measures the cost-effectiveness of medicines.

Novartis decided midway through to slash the number of patients from 17,000 to 10,000. Ridker’s hopes for the trial results were relatively modest — at least enough data to point to clear next steps for science — "that we could finally say, ‘Here’s the first evidence for lowering inflammation,’ ” he said.

When researchers finally learned which patients were on the drug and which were on a placebo this summer, the results exceeded his hopes on cardiovascular measures and carried an intriguing hint about a striking reduction in the incidence of fatal lung cancer.

Barnett Kramer, director of the Division of Cancer Prevention at the National Cancer Institute, said it was unclear whether the effect was preventive or therapeutic — or even whether it was a chance finding — without a trial specifically designed to further test the idea.