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 Cempra's shares fell as much as 41 percent on the news.
The review, posted on the FDA's website on Wednesday, comes two days
ahead of a meeting of outside experts who will discuss the drug,
solithromycin, and recommend whether or not it should be approved.
The FDA is not obliged to follow its advisory panel's advice but
typically does so.
"A significant safety signal for hepatotoxicity was observed in the
solithromycin development program," agency reviewers noted. Another
area of concern, they said, was "the high rate of infusion
site-related reactions."
Solithromycin is descended from a notorious drug made by Sanofi SA
called Ketek, or telithromycin, which was approved by the FDA in
2004 but later linked to dozens of serious or fatal liver problems
and largely withdrawn.
Cempra constructed the same drug but without the elements it
believes were responsible for the side effects associated with Ketek,
which included visual, neurological and liver problems. The company
is seeking approval for an oral and intravenous version of
solithromycin.
Clinical trials show solithromycin to be as effective as the
antibiotic moxifloxacin, the FDA said in its review, but rates of
liver enzyme elevations were higher in patients treated with
solithromycin than with moxifloxacin. High liver enzymes can be a
signal of an underlying liver problem, especially if they remain
elevated.
In the Cempra trials enzyme elevations were transitory. Patients did
not develop clinical symptoms of liver problems, such as jaundice,
and there was no evidence of acute liver damage.
Nonetheless the FDA is likely to be especially cautious as the Ketek
episode was scarring for the agency. It prompted Congressional
investigations and accusations from FDA insiders that the agency
stifled concerns over the drug voiced by its own reviewers and
dismissed suspicious clinical data that was later shown to be
fraudulent.
"We think the institutional memory of Ketek will force the division
into a highly conservative and defensive stance on solithromycin's
safety profile," Ritu Baral, analyst at Cowen and Company, said in a
recent research note.
Even so, she said, "we believe the agency would respect what we see
as a likely positive panel vote for approval."
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Solithromycin belongs to a class of antibiotics known as macrolides
that include erythromycin, clarithromycin and azithromycin and are
used to treat a wide range of bacterial infections. Roughly 50
percent of the most common bacterium, the pneumococcus that cause
chest and other infections, are resistant to macrolides, making the
quest for new antibiotics pressing.
The advisory panel will be asked to assess whether the efficacy of
solithromycin in treating infections that kill more than 50,000
people a year in the United States outweigh a potential risk of
liver toxicity.
"Although we expect a positive vote and approval, potential adverse
outcomes for Cempra include a request for a large safety trial to
further characterize risks," Alan Carr, analyst at Needham &
Company, said in a research note.
If approved, he sees the drug generating peak worldwide sales of $2
billion.
Pharmaceutical companies have been slow to develop new antibiotics.
Solithromycin would be the first oral and intravenous antibiotic for
community-acquired pneumonia since moxifloxacin in 1999. Since then
several oral-only or intravenous-only drugs have been developed.
Cempra's shares fell as low as $10.90 in morning trade on Nasdaq
from a close on Tuesday of $18.60.
(Reporting by Toni Clarke in Washington; Editing by Meredith
Mazzilli)
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