Sirturo (bedaquiline)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Approval Status:

Approved December 2012

Specific Treatments:

multi-drug resistant tuberculosis

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General Information

Sirturo (bedaquiline) is a diarylquinoline antimycobacterial. It specifically inhibits mycobacterial ATP-synthase, responsible for the cell's energy production.

Sirturo is specifically indicated as part of combination therapy in adults with pulmonary multi-drug resistant tuberculosis.

Sirturo is supplied as a tablet for oral administration. Sirturo should only be used in combination with at least 3 other drugs to which the patient’s MDR-TB isolate has been shown to be susceptible in vitro. If in vitro testing results are unavailable, treatment may be initiated with Sirturo in combination with at least 4 other drugs to which the patient's MDR-TB isolate is likely to be susceptible. The recommended dosage of Sirturo is as follows: Weeks 1-2: 400 mg (4 tablets of 100 mg) once daily with food. Weeks 3-24: 200 mg (2 tablets of 100 mg) 3 times per week with food (with at least 48 hours between doses) for a total dose of 600 mg per week. The tablet should be swallowed whole with water.

Clinical Results

FDA Approval
The FDA approval of Sirturo was based on two studies.
Study 1
The placebo-controlled, double-blind, randomized trial enrolled 160 newly diagnosed patients with multi-drug resistant pulmonary Mycobacterium tuberculosis. Subjects were randomized to receive treatment with either Sirturo or placebo, both with other drugs used to treat MDR-TB. Sirturo was administered as 400 mg once daily for the first 2 weeks and as 200 mg 3 times per week for the following 22 weeks. After the 24-week Sirturo or placebo treatment phase, subjects continued to receive their other drugs used to treat MDR-TB until a total treatment duration of 18 to 24 months. The Sirturo treatment group had a decreased time to culture conversion and improved culture conversion rates compared to the placebo treatment group at Week 24. Treatment success was reached by 77.6% of the Sirturo arm versus 57.6% of the placebo arm at Week 24 (p=0.014). At Week 72 success was reached by 70.1% and 56.1% of the respective arms. Median time to culture conversion was 83 days for the Sirturo treatment group compared to 125 days for the placebo treatment group.
Study 2
This placebo controlled study was designed similarly to Study 1 except that Sirturo or placebo was given for only 8 weeks instead of 24 weeks. A total of 47 subjects were treated. The Sirturo treatment group had a decreased time to culture conversion and improved culture conversion rates compared to the placebo treatment group at Week 8. At Weeks 8 and 24, the differences in culture conversion proportions were 38.9% (p-value: 0.004) and 15.7% (p-value: 0.32) respectively.

Side Effects

Adverse events associated with the use of Sirturo may include, but are not limited to, the following:

  • nausea
  • arthralgia
  • headache

Mechanism of Action

Bedaquiline is a diarylquinoline antimycobacterial drug that inhibits mycobacterial ATP (adenosine 5'-triphosphate) synthase, an enzyme that is essential for the generation of energy in Mycobacterium tuberculosis.

Literature References

Diacon AH, Donald PR, Pym A, Grobusch M, Patientia RF, Mahanyele R, Bantubani N, Narasimooloo R, De Marez T, van Heeswijk R, Lounis N, Meyvisch P, Andries K, McNeeley DF Randomized pilot trial of eight weeks of bedaquiline (TMC207) treatment for multidrug-resistant tuberculosis: long-term outcome, tolerability, and effect on emergence of drug resistance. Antimicrobial Agents and Chemotherapy 2012 Jun;56(6):3271-6

Additional Information

For additional information regarding Sirturo or multidrug-resistant tuberculosis, please visit the Janssen Therapeutics web page.