CHICAGO Oct 24 New federal guidelines expand the range of patients who might benefit from Johnson & Johnson's Sirturo drug for the treatment of multi-drug-resistant tuberculosis (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. Centers for Disease Control and Prevention, go beyond the narrow group of adults listed in the drug's label, offering advice on use of the treatment in children, pregnant women and individuals with other health complications, such as diabetes and HIV infection.
The guidance on how best to use Sirturo comes as rates of MDR-TB continue to climb, said Dr. Sundari Mase of the CDC's TB elimination branch and lead author of the guidelines, published in the CDC's Morbidity and Mortality Weekly Report.
Although TB infection is rare in the United States, it has become a global public health threat as poor oversight of available drugs has spawned strains of the bacterium that resist treatment by all but a handful of drugs.
In its annual TB report issued this week, the World Health Organization said 8.6 million people developed TB in 2012 and 1.3 million died from the disease. It warned that 3 million people with TB are being missed by health systems, and drug-resistant "superbug" strains of the bacterial infection have put progress against TB at risk.
According to the report, 450,000 people fell ill with MDR-TB in 27 countries in 2012, with China, India and Russia worst affected.
"Right now, the United States is the only country in the world implementing this drug and rolling it out," Mase said, adding that China is close behind.
The drug, known generically as bedaquiline, was approved by the U.S. Food and Drug Administration last December for MDR-TB as part of combination therapy in adults over the age of 18 with TB infections of the lung.
The approval was based on the available data, but the drug had not been studied in other populations at high risk for the infection.
The CDC's guidelines offer advice on so-called "off label" uses of the treatment for categories of patients with drug-resistant strains of TB that have not yet been studied, said Mase. She noted that most drugs used to treat TB are "off label."
"Our expert consultants felt that the lack of data did not necessarily mean the drug should not be used in these populations if the risk of not getting appropriate treatment would lead to a really poor outcome - death or (serious illness)," Mase said.
Clinical trials of the J&J drug showed an increased risk of death among patients who got the treatment compared with a placebo group, data Mase said the panel weighed carefully.
When the FDA approved the treatment, it did so with the caveat that J&J must collect detailed data on its use, closely tracking side effects.
Mase said the available data do not reveal a clear pattern of deaths to show they were caused by bedaquiline.
"Given that safety concern was there, the group thought if we closely monitor patients and are able to pick up serious adverse events, and side effects are reported and investigated quickly, there should be no reason to limit who gets the drug just based on the increase in all-cause mortality," she said.
Treating typical TB cases is a long process, with patients needing to take a cocktail of powerful antibiotics for six months. Many patients fail to complete their treatment, a factor which has fueled a rise in the drug-resistant forms.
"The overriding imperative is that this drug be used appropriately," Chrispin Kambili, global medical affairs leader for J&J's Janssen division, said in a telephone interview.
Kambili said the CDC guidelines and those that the World Health Organization released in June include careful language intended to safeguard the drug from the development of drug resistance, as has happened with many of the existing antibiotics that have been used to treat TB over the years.
Among leaders in TB, Kambili said, "there is a lot of agreement that we have to take care of this almost rare occurrence where a new TB drug has been introduced" so that "the risk of squandering this drug is minimized."
The new CDC guidelines add more specifications for monitoring patients and require that the J&J drug be used with at least four other drugs in patients whose lab tests show they have MDR-TB, and it must be used with five other TB drugs in patients with less clear diagnoses.
The panel also said that for certain patients, the drug could be used for longer than 24 weeks, even though it has not been studied in patients for longer than that.
Mase said the panel felt if a patient has been doing well with the first 24-week course of treatment, "there should be no reason not to extend treatment beyond 24 weeks."
The guidelines also specify dosing, the importance of direct observation to ensure treatment is taken consistently, and the need for doctors to use the treatment only in consultation with an expert in MDR-TB, which will help the CDC keep close tabs on how the drug is used.