Tuberculosis - TMC-207

Tuberculosis remains a major cause of death globally, not least because of the emergence of strains that are resistant to most antibiotic drugs. Co-infection with HIV exacerbates the situation.

The fact that long courses of drugs need to be taken to eradicate the virus does not help either - this enhances the danger of resistance developing. New drugs that are active against Mycobacterium tuberculosis are very much needed, and ones that shorten the length of treatment would be extremely valuable in the fight against TB.

One new antituberculosis drug, TMC-207, is being developed by Johnson & Johnson subsidiary Tibotec.¹ It has a new mechanism of action, as it interacts with the F0 subunit of mycobacterial ATP synthase, and in the lab showed good activity against a wide range of strains of the bacterium, including those that are resistant to existing antituberculosis drugs.

In one early clinical trial, 75 treatment naïve patients were given 25, 100 or 400mg of TMC-207 once a day, 600mg rifampin or 300mg isoniazid for seven days.² The highest dose of the new drug had significant bactericidal activity after four days, with a similar magnitude to the other two drugs. No drug-related serious adverse events were observed.

In the first stage of a two-stage randomised, controlled Phase II trial, 47 patients with newly diagosed multidrug resistant pulmonary tuberculosis were given 400mg of TMC-207 for two weeks, followed by 200mg three times a week for six weeks, or placebo, in combination with a standard five drug second line anti-tuberculosis regimen.³ They found that adding the new drug to the cocktail reduced the time before a negative sputum culture was achieved; 45% of those given TMC-207 achieved a negative culture compared with 9% of the placebo group. Most adverse events were mild to moderate. Trials continue.