By Toni Clarke
WASHINGTON Jan 14 The U.S. Food and Drug
Administration appears skeptical that data submitted by Johnson
& Johnson proves its anticoagulant Xarelto is effective
in reducing the risk of further heart problems in patients who
have recently suffered a heart attack.
The agency questioned the way in which J&J analyzed clinical
trial data, and said there was no convincing proof the drug
confers significant benefit or fills an unmet medical need,
given that there are other therapies on the market.
The review was posted on the FDA's website on Tuesday, two
days ahead of a meeting of outside experts who will discuss the
drug, also known as rivaroxaban, and recommend whether it should
Xarelto is already used to treat and prevent deep vein
thrombosis and pulmonary embolisms and to reduce the risk of
stroke and blood clots in patients with an irregular heart beat
that is not caused by heart problems.
Now the company is hoping it will also be approved for
patients with acute coronary syndrome (ACS), an umbrella term
covering any condition brought on by a sudden, reduced blood
flow to the heart, including heart attack and chest pain.
Some analysts are doubtful.
"Based on our review of this material, we continue to have
low expectation of approval," Larry Biegelsen, an analyst at
Wells Fargo Securities, said in a research note. However, he
expects sales of the drug to rise to $1.2 billion in 2015 from
an estimated $703 million in 2013 based on the indications for
which it is approved.
"We expect the ACS potential to be modest even if approved,"
J&J originally filed for approval of Xarelto in ACS at the
end of 2011. The FDA rejected the application, saying efficacy
data was not strong enough to support approval. The company
provided additional information but the FDA once again declined
to approve the drug, prompting J&J to appeal the decision.
The FDA denied the appeal but said limiting the duration of
use to one month might be a pathway forward because efficacy was
more evident and the risk of bleeding, a side effect of the
drug, was lower during this period. J&J filed a new application
seeking a treatment duration of 90 days.
The FDA's latest review suggests the agency remains
"It is unclear how to choose the metric for determining when
the benefit of rivaroxaban is greatest," the review found. "Not
only does the effect of rivaroxaban not appear to be greater
earlier, but an effect in the first 90 days or so is not
apparent at all."
Dr. Paul Burton, vice president of clinical development at
Janssen Research and Development, a J&J unit, defended the drug,
saying the company believes that when added to standard
treatments it "delivers a strong incremental benefit by
significantly reducing the risk of cardiovascular events,
including death, at a time when patients are at the highest
The FDA's review also questioned whether the benefit of the
drug outweighs the heightened risk of bleeding since two other
drugs, Eli Lilly & Co's Effient and AstraZeneca
Plc's Brilinta, are currently approved for ACS.
J&J's proposed prescribing information would warn that
treatment in combination with the Effient, known also as
prasugrel, and Brilinta, also known as ticagrelor, has not been
studied and is not recommended because of the risk of bleeding.
Xarelto would therefore only be available as an add-on to
Bristol-Myers Squibb Co's antiplatelet Plavix, or
"There are no data demonstrating that ACS patients treated
with clopidogrel plus rivaroxaban will have superior outcomes
compared to treatment with prasugrel or ticagrelor," the review
said. "So rivaroxaban does not provide therapy for an unmet
And while treatment for a limited duration "has an intuitive
appeal," the review said, "the task for the analyses of the
effect of rivaroxaban over time is not to pick a time period in
which the benefit-risk is acceptable."