* FDA panel says data support drug efficacy
* Panel backs safety, despite heart, liver safety concerns
* J&J aims for accelerated approval of novel medicine
(Adds J&J comments, drug data)
By Ransdell Pierson
Nov 28 An advisory panel to the U.S. Food and
Drug Administration on Wednesday voted that an experimental
Johnson & Johnson drug for multidrug-resistant
tuberculosis appears to be safe and effective, but highlighted
potential heart and liver-safety issues.
The medicine, called bedaquiline, targets adenosine
triphosphate synthase, an enzyme the tuberculosis bacterium
needs to generate its energy. If approved, J&J said it would be
the first drug in 40 years with a new mechanism of action
J&J said the panel of outside medical experts, in a vote of
18 to 0, found that trial data provide "substantial evidence" of
efficacy and safety for bedaquiline in adults, taken in
combination with standard treatments. It backed the drug's
safety, by a vote of 11 to 7.
The FDA usually follows the advice of its advisory panels
when deciding whether to approve new medicines.
In September, the FDA granted priority review of the drug,
based on data from two mid-stage trials that tested it among
patients with tuberculosis that is resistant to standard drugs.
J&J's Janssen drug subsidiary is hoping the agency will
grant accelerated approval of its drug, on the basis of
favorable data from mid-stage trials. The company plans to begin
a larger Phase 3 study early next year.
In a pair of completed Phase 2 trials, two doses of the
medicine were tested for 24 weeks, in combination with standard
treatments, followed by continuation of standard therapy for a
year to 18 months.
In one of the trials, 10 deaths were seen among 79 people
taking bedaquiline and standard drugs, compared with only 2
deaths among 81 patients taking only standard drugs.
Some members of the FDA advisory panel expressed concern
about that "mortality imbalance," as well as elevated liver
enzymes -- a potential sign of liver toxicity -- among patients
taking the J&J drug.
Patients taking bedaquiline also had increases in the
so-called QT interval -- suggesting a possible electrical
irregularity in the heart -- than those not taking the medicine.
But Wim Parys, Janssen's head of development for infectious
disease medicines, said in an interview that the drug's
superiority to standard medicines in the mid-stage trials held
sway with the advisory panel.
He said 21 percent fewer patients taking the J&J drug still
had signs of the TB bacterium in their sputum after one of the
mid-stage studies, than those taking just standard drugs.
"This is a new mechanism of action to treat TB, particularly
(bacteria) that have become resistant to first-line treatments,"
Cowen and Co has forecast peak annual sales of $300 million
for bedaquiline, which would make it a fairly modest product for
the diversified healthcare company.
Parys acknowledged the drug's limited sales potential, given
that it would be used mainly in poorer developing countries. But
he said J&J approved development of the medicine due to a
compelling medical need.
The planned larger trial will involve nine months of
treatment with bedaquiline, in combination with standard drugs,
compared with standard drugs alone for the same period. The
total nine-month treatment period would be far shorter than the
current 18- to 24-month treatment period for multidrug-resistant
tuberculosis drugs recommended by the World Health Organization,
Multidrug-resistant tuberculosis is caused by strains of the
bacterium that have become resistant to at least isoniazid and
rifampin, the two most potent drugs for TB.
Resistance to anti-TB drugs can occur when they are misused
or mismanaged, for instance when patients don't complete their
full course of treatment or when doctors prescribe the wrong
treatment, wrong dose or length of time taking the drugs.
An estimated 8.7 million people in 2011 fell ill with
tuberculosis - which is spread by coughing and sneezing -- while
1.4 million died from the disease, according to the World Health
Organization. About 310,000 cases of multidrug-resistant TB were
reported the same year, the organization said, with almost 60
percent in India, China and Russia.
(Reporting by Ransdell Pierson; Editing by Jan Paschal and