(Updates with Novartis comment, sales estimates)
By Toni Clarke
WASHINGTON, March 25 A drug to treat acute heart failure made by Novartis AG should not be approved because there is insufficient evidence to show it improves symptoms, according to an initial review by the U.S. Food and Drug Administration.
The review, posted on the FDA's website on Tuesday, comes two days ahead of a meeting of outside advisors who will make their own recommendation on whether the drug should be approved. The FDA is not obliged to follow the advice of its advisory panels but typically does so.
Acute heart failure is a medical emergency in which patients become short of breath as the heart struggles to pump blood and fluid around the body. The drug, serelaxin, is a genetically engineered hormone that relaxes blood vessels and eases the burden on the heart.
"We recommend that serelaxin not be approved at this time because there is insufficient evidence to support the proposed indication to "improve the symptoms of acute heart failure through reduction of the rate of worsening of heart failure," the reviewers said. "We did not identify any significant safety concerns precluding approval."
Novartis, based in Basel, Switzerland, said in a statement that it believes the drug "demonstrates a clinically significant beneficial effect in patients with AHF, with an overall favorable benefit-risk profile". If approved, the drug would be sold under the brand name Reasanz.
About 5 million people in the United States are living with chronic heart failure, a progressive weakening of the heart, according to Novartis. About 1 million are hospitalized with episodes of acute heart failure, and about 22 percent of patients who are hospitalized die within a year.
If approved, the drug is expected to generate sales of $713 million by 2018 according to the average estimate of five analysts polled by Thomson Reuters.
Novartis filed for approval of serelaxin based on a single study which showed that when given alongside standard treatment, it alleviated shortness of breath by slowing the rate of worsening heart failure following hospitalization.
Results showed the drug reduced deaths by 37 percent compared with patients in the control group after six months of treatment.
The FDA said it generally requires evidence from two independent trials to show an improvement in symptoms. Moreover, the reviewers said that the data did not capture symptoms of acute heart failure other than dyspnea, or shortness of breath, such as cough, choking, fatigue and anxiety.
"Therefore, the current evidence does not support a broad claim related to the symptoms of acute heart failure," they said, adding that the trial results "do not provide persuasive evidence of an effect on dyspnea".
The reviewers also said they did not believe data from the trial supported the claim that serelaxin reduced the rate of worsening heart failure, which Novartis claims.
The data was not well characterized or captured "and is therefore hard to interpret," they said.
If the FDA ultimately decides that the data are sufficient to support approval, the reviewers said, "there are no reservations from a safety perspective significant enough to militate against approval."
European regulators also recommended against approving the drug. Novartis has asked European regulators to grant it conditional approval pending the results of a second clinical trial.
The FDA is scheduled to rule on whether to approve the drug by May 17.
(Reporting by Toni Clarke in Washington; Editing by Stephen Powell)