(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
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
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
The FDA is scheduled to rule on whether to approve the drug
by May 17.
(Reporting by Toni Clarke in Washington; Editing by Stephen