U.S. guidelines expand potential uses of J&J TB drug


By Julie Steenhuysen

CHICAGO, Oct 24 (Reuters) - New federal guidelines expandthe range of patients who might benefit from Johnson & Johnson's Sirturo drug for the treatment of multi-drug-resistanttuberculosis (MDR-TB), the first new type of TB drug to win U.S.regulatory approval in more than 40 years.

The recommendations, issued on Thursday by the U.S. Centersfor Disease Control and Prevention, go beyond the narrow groupof adults listed in the drug's label, offering advice on use ofthe treatment in children, pregnant women and individuals withother health complications, such as diabetes and HIV infection.

The guidance on how best to use Sirturo comes as rates ofMDR-TB continue to climb, said Dr. Sundari Mase of the CDC's TBelimination branch and lead author of the guidelines, publishedin the CDC's Morbidity and Mortality Weekly Report.

Although TB infection is rare in the United States, it hasbecome a global public health threat as poor oversight ofavailable drugs has spawned strains of the bacterium that resisttreatment by all but a handful of drugs.

In its annual TB report issued this week, the World HealthOrganization said 8.6 million people developed TB in 2012 and1.3 million died from the disease. It warned that 3 millionpeople with TB are being missed by health systems, anddrug-resistant "superbug" strains of the bacterial infectionhave put progress against TB at risk.

According to the report, 450,000 people fell ill with MDR-TBin 27 countries in 2012, with China, India and Russia worstaffected.

"Right now, the United States is the only country in theworld implementing this drug and rolling it out," Mase said,adding that China is close behind.

The drug, known generically as bedaquiline, was approved bythe U.S. Food and Drug Administration last December for MDR-TBas part of combination therapy in adults over the age of 18 withTB infections of the lung.

The approval was based on the available data, but the drughad not been studied in other populations at high risk for theinfection.

The CDC's guidelines offer advice on so-called "off label"uses of the treatment for categories of patients withdrug-resistant strains of TB that have not yet been studied,said Mase. She noted that most drugs used to treat TB are "offlabel."

"Our expert consultants felt that the lack of data did notnecessarily mean the drug should not be used in thesepopulations if the risk of not getting appropriate treatmentwould lead to a really poor outcome - death or (seriousillness)," Mase said.

Clinical trials of the J&J drug showed an increased risk ofdeath among patients who got the treatment compared with aplacebo group, data Mase said the panel weighed carefully.

When the FDA approved the treatment, it did so with thecaveat that J&J must collect detailed data on its use, closelytracking side effects.

Mase said the available data do not reveal a clear patternof deaths to show they were caused by bedaquiline.

"Given that safety concern was there, the group thought ifwe closely monitor patients and are able to pick up seriousadverse events, and side effects are reported and investigatedquickly, there should be no reason to limit who gets the drugjust based on the increase in all-cause mortality," she said.

Treating typical TB cases is a long process, with patientsneeding to take a cocktail of powerful antibiotics for sixmonths. Many patients fail to complete their treatment, a factorwhich has fueled a rise in the drug-resistant forms.

"The overriding imperative is that this drug be usedappropriately," Chrispin Kambili, global medical affairs leaderfor J&J's Janssen division, said in a telephone interview.

Kambili said the CDC guidelines and those that the WorldHealth Organization released in June include careful languageintended to safeguard the drug from the development of drugresistance, as has happened with many of the existingantibiotics that have been used to treat TB over the years.

Among leaders in TB, Kambili said, "there is a lot ofagreement that we have to take care of this almost rareoccurrence where a new TB drug has been introduced" so that "therisk of squandering this drug is minimized."

The new CDC guidelines add more specifications formonitoring patients and require that the J&J drug be used withat least four other drugs in patients whose lab tests show theyhave MDR-TB, and it must be used with five other TB drugs inpatients with less clear diagnoses.

The panel also said that for certain patients, the drugcould be used for longer than 24 weeks, even though it has notbeen studied in patients for longer than that.

Mase said the panel felt if a patient has been doing wellwith the first 24-week course of treatment, "there should be noreason not to extend treatment beyond 24 weeks."

The guidelines also specify dosing, the importance of directobservation to ensure treatment is taken consistently, and theneed for doctors to use the treatment only in consultation withan expert in MDR-TB, which will help the CDC keep close tabs onhow the drug is used.

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