Novartis AG is developing a version of a hormone found in pregnant women in a bid to reduce deaths from heart failure.
RLX030, an experimental drug that’s a man-made version of the hormone, reduced death rates by 37 percent in patients with a common condition called acute heart failure six months after treatment, according to a clinical trial presented yesterday at the American Heart Association meeting in Los Angeles. The medicine is the only treatment to lower mortality, the company said in a statement today.
Novartis stands to gain $1 billion in annual sales by 2018 if RLX030 makes it to market, according to Seamus Fernandez, an analyst with Leerink Swann & Co. in Boston. First the Basel, Switzerland-based company must convince regulators and doctors that the result of the relatively small trial wasn’t a fluke, said Milton Packer of the University of Texas Southwestern Medical Center in Dallas.
“If that mortality benefit is real, boy are we going to be excited,’” said Packer, who chairs the center’s department of clinical sciences and wasn’t involved in the 1,161-person trial. “The real question is whether the mortality difference seen in this trial is a true and replicable finding.”
Novartis plans to submit the drug, also referred to as Relaxin, to U.S. regulators next year. The company doesn’t think it will need another clinical trial to receive marketing approval, said Ameet Nathwani, who is in charge of Novartis’s critical care products.
“Our perspective is that our data is robust,” Nathwani said in an interview before the study was released.
Acute heart failure often occurs in the wake of other trouble such as hypertension, diabetes or coronary artery disease and may strike about one in 10 people over the age of 65. Doctors now use a mix of drugs and devices to help patients feel better; still, half of those hospitalized don’t survive longer than five years. RLX030 is a manufactured copy of relaxin-2, a hormone whose levels rise during pregnancy.
Doctors say heart failure is like “drowning alive,” as fluid rapidly collects in the lungs. Patients experience shortness of breath and a swelling of their limbs, coughing, weakness, fatigue and an irregular heartbeat.
In the acute version, there can be a sudden worsening of the chronic condition, in which the heart muscle loses its ability to pump blood.
The hormone, first found in pocket gophers by an American zoologist in the 1920s, is thought to relax blood vessels in pregnant women. Researchers now believe that it helps heart patients by protecting heart cells and kidney function, Nathwani said.
Together with the experimental compound LCZ696, Relaxin may help Novartis build a portfolio of heart-failure drugs. The company needs to replenish its product line-up as the heart drug Diovan and the cancer treatment Gleevec, its biggest sellers, start to lose patent protection. They make up about 18 percent of Novartis’s $58.6 billion in annual revenue.
Novartis acquired Relaxin in the 2010 purchase of closely held Corthera Inc.
Cardiologists at the AHA meeting are getting the first detailed look at the late-stage study known as RELAX-AHF. Novartis released bare-bones results in September.
Besides reducing death rates, Relaxin helped ease shortness of breath, which is one of the most common symptoms of acute heart failure, according to the study. Helping patients breathe easier was the main goal of the study, which looked at death rates as a secondary measure.
Still, the drug didn’t keep patients out of the hospital in the 60 days after the intervention. Also, RLX030 cut neither cardiovascular deaths nor heart or kidney failure after 60 days, which were secondary goals of the study.
This may make doctors cautious about whether the drug’s effect on mortality will hold up in a hospital setting, said John McMurray, professor of cardiology at the University of Glasgow School of Medicine in Scotland. Another concern is the small number of deaths, with 41 in the Relaxin arm, and 64 in the placebo group, he said.
“Small numbers often don’t give you robust and reliable estimates of benefit,” he said. “If we did replicate this finding, it would be an extraordinary advance in the management of acute heart failure, for which we have no disease-modifying or life-saving therapies.”
The drug didn’t show any serious safety issues in the study. “It’s very comforting that women have high levels of Relaxin during nine months,” Nathwani said. “It looks incredibly well tolerated.”
An additional caveat may be the shadow of Natrecor, a Johnson & Johnson drug introduced in 2001, according to Tim Anderson, an analyst with Sanford C. Bernstein & Co. in New York.
Natrecor, given intravenously, was one of the first drugs for congestive heart failure when it was approved, and in 2004 it generated $230 million in revenue. Sales were more than halved in 2006 after reviews of its use in less than 1,000 patients tied the medicine to worsening kidney function and higher death rates. A later study of 7,141 patients found the drug to be safe, though it only slightly improved symptoms.
“Unfortunately, this sets the bar high for Relaxin,” Anderson said in a note yesterday.