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J&J's Bedaquiline Advisory Cmte. Could Test Strength Of Phase II Argument For Tuberulosis Drugs
  26 September 2012 01:15 EDT
'The Pink Sheet' DAILY

Elsevier Business Intelligence: 'The Pink Sheet' DAILY - September 25, 2012

Of three compounds vying to be the first new treatment FDA approves for tuberculosis in more than four decades, Johnson & Johnson 's bedaquiline has gained a strong head start with the agency asking its Anti-Infective Drugs Advisory Committee to review it at its Nov. 28 meeting.

J&J filed an NDA seeking accelerated approval for bedaquiline, also called TMC-207, on June 29 ("Johnson amp Johnson Files NDA Seeking Accelerated Approval Of Bedaquiline In Tuberculosis" "The Pink Sheet Daily" Jul. 2, 2012). The company announced Sept. 5 that FDA has granted priority review, which means the Prescription Drug User Fee Act deadline should be Dec. 29.

Originally developed by Tibotec Group NV , now a part of J&J subsidiary Janssen Research and Development the drug is a diarylquinolone and an oral treatment to be used in combination therapy in pulmonary, multi-drug resistant tuberculosis.

According to the TB Alliance, bedaquiline should be eligible for a tropical disease priority review voucher from FDA, a program the agency is trying to make more appealing by reducing the review costs for redeeming one ("FDA Cuts Priority Review Voucher Fee By 32 No Takers For FY 2013" "The Pink Sheet" Sep. 17, 2012).

If bedaquiline does earn J&J a voucher if it is approved, it would be apparently only the second drug to earn such a designation, following FDA's April 2009 award to Novartis AG for the antimalarial drug Coartem (artemether / lumefantrine)("Novartis Gambles Priority Review Voucher On iIlarisi Gout Indication" "The Pink Sheet" Jun. 27, 2011). This award did not prevent Novartis from receiving a "complete response" letter from FDA when it invoked the voucher for its gout drug Ilaris (canakinumab) ("Novartis Takes Stock Of Ilaris For Gout Following FDAs Complete Response Letter" "The Pink Sheet Daily" Aug. 29, 2011).

Success In Phase II

Bedaquiline has been tested in two Phase II studies, with a Phase III trial slated to begin in the fourth quarter of this year. In June 2009, an article in the New England Journal of Medicine reported that in the first stage of one of these trials, "the addition of TMC207 to standard therapy for multidrug-resistant tuberculosis reduced the time to conversion to a negative sputum culture, as compared with placebo (hazard ratio, 11.8; 95% confidence interval, 2.3 to 61.3; P=0.003 by Cox regression analysis) and increased the proportion of patients with conversion of sputum culture (48% vs. 9%)."

"The mean log10 count of colony-forming units in the sputum declined more rapidly in the TMC207 group than in the placebo group," the article added. The other trial is an open-label study.

The drug also is part of the Phase II New Combination 1 or NC001 study sponsored by the Global Alliance for TB Drug Development, along with moxifloxacin and Novartis AG 's PA-824 ("TB Study Lights Pathway Toward Combination Drug Trial Guidance" "The Pink Sheet" Dec. 20, 2010). If approved, it would be the first drug for that indication as well as the first new approved therapy with a new mechanism of action for TB in more than 40 years.

The other two drugs are still years away from use. "The REMox TB trial investigating a 4-month moxifloxacin regimen has completed enrollment and treatment of patients, but currently still in the process of following up with certain patients. Application for an NDA for moxifloxacin for TB is not scheduled to occur prior to 2014," the TB Alliance said in an email.

"Regarding PA-824, as of now it is not intended that PA-824 will be developed as an individual drug, but rather as a part of a combination regimen. PA-824 will likely enter a Phase III trial in combination with other new drugs, be they the PaMZ drugs or a future regimen not yet involved in clinical testing. So, the schedule for PA-824 filing an NDA is essentially that of the experimental regimen to which it belongs."

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