Bedaquiline, the first agent in a new class
of TB drug, has been recommended for accelerated approval by the Anti-Infective
Drugs Advisory Committee of the United States Food and Drug Administration
The committee voted unanimously (18 to 0) that
the efficacy findings from studies of bedaquiline support the proposed
indication for the treatment of multidrug-resistant tuberculosis (MDR-TB) as
part of combination therapy in adults. The committee also agreed that the
safety findings supported the proposed indication, by a vote of 11 to 7.
activist organisation Treatment Action Group (TAG), along with the Global TB
Community Advisory Board (TB CAB), HIV i-Base, South Africa’s Treatment Action
Campaign (TAC), Médecins sans Frontières (MSF) and the
Southern African HIV Clinicians’ Society, support early appropriate access to
bedaquiline for patients with drug-resistant TB (DR-TB).
a statement to the committee Mark Harrington, Executive Director of TAG, said: “If
the FDA grants approval to bedaquiline, it will provide a major incentive for
new sponsors and companies to introduce more new drugs, classes, compounds,
combinations, and regimens into the clinical pipeline.”
Although TAG welcomed
the FDA’s review, Harrington cautioned that the FDA
should stipulate that the necessary and required post-marketing studies must be
conducted. He called for:
cardiac studies of important potential
drug-drug interactions such as with Otsuka’s delamanid (OPC67683), the
nitroimidazooxazole recently submitted for review by the European Medicines
drug-drug interaction studies with
commonly used antiretroviral therapies such as atazanavir, darunavir,
efavirenz, raltegravir, and other drugs likely to be used in combination by
people with HIV and MDR-TB.
appropriate, rationally designed studies
of optimal regimens to treat drug-sensitive TB (DS-TB), DR-TB, and latent TB
development of appropriate genotypic
and phenotypic drug susceptibility and resistance surveillance (DST, DRS) tests
to help guide practice and protect patients from the emergence of unnecessary
Bedaquiline is a
diarylquinoline and is the first drug in this class for the treatment of
drug-resistant TB. It is patented by Janssen Pharmaceuticals, a subsidiary of
Johnson & Johnson.
In a phase II
randomised controlled trial, bedaquiline was given to 23 patients and placebo to
24 patients, for eight weeks. All participants received standard MDR-TB regimens as
well. Bedaquiline significantly reduced the time-to-culture conversion during
24 weeks of follow-up (HR 2.3; 95%CI: 1.1 - 4.7; p=0.03). Forty-eight per cent of the patients
on bedaquiline became sputum-negative versus 9% of patients on placebo.
Nausea was the only
adverse event reported to occur significantly more often in the bedaquiline
group (26 vs 4%, p=0.04). A study with two-year follow up data has been
published and confirms the initial outcomes.
data from an open-label trial of bedaquiline in approximately 200 participants show
that adding bedaquiline to an individualised MDR-TB regimen was well tolerated
and resulted in an overall 81% culture conversion rate at week 24, with median
times to culture conversion of 8 weeks for patients with MDR-TB, 12 weeks for
patients with pre-extensively drug-resistant TB (XDR-TB), and 24 weeks for patients with XDR-TB.
A phase 1 study in healthy volunteers showed no substantial reduction in bedaquiline levels
when coadministered with efavirenz.
QT prolongation has
been observed in patients treated with bedaquiline. The QT interval is a measure of the time between the start of the Q
wave and the end of the T wave in the heart's electrical cycle. A prolonged QT
interval is a risk factor for cardiac arrhythmias. Further safety data on the
effects of bedaquiline on the QT interval are needed.