By Julie Steenhuysen
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
"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
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
"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.