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 against tuberculosis.
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," Parys said.
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, J&J said.
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 Carol Bishopric)
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