The US Food and Drug Administration approved Pretomanid tablets as part of a three-drug combination regimen together with linezolid (Zyvox) and Johnson & Johnson’s bedaquiline (Sirturo) for the treatment of a specific type of highly treatment-resistant tuberculosis (TB) of the lungs.
TB is a bacterial infection that caused about 1.6 million deaths globally in 2017. It spreads through droplets when someone sick with TB sneezes or coughs. TB primarily attacks the lungs but can sometimes affect other organs.
Multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) are forms of tuberculosis that do not respond to first-line anti-TB drugs. XDR-TB, a more serious form of MDR-TB, is unresponsive even to the two most powerful anti-TB drugs – isoniazid and rifampicin – in addition to being resistant to certain second-line treatments.
Only a small fraction of the 10 million people infected by TB each year get drug-resistant TB, but very few of those who do survive it. According to the World Health Organization, in 2016, there were an estimated 490,000 new cases of multidrug-resistant TB worldwide, with a smaller portion of cases of extensively drug-resistant TB.
The safety and efficacy of Pretomanid, taken orally in combination with bedaquiline and linezolid, was primarily demonstrated in a study of 109 patients with extensively drug-resistant, treatment intolerant or non-responsive multidrug-resistant pulmonary TB (of the lungs).
Of the 107 patients who were evaluated six months after the end of therapy, 95 (89%) were successes, which significantly exceeded the historical success rates for treatment of XDR- TB. Many TB patients are also infected with HIV. In the trial, the treatment worked as well for them as it did for other study participants. The drug regimen also appears to stop patients spreading the deadly bacterial infection after a few days’ treatment.
The most common adverse reactions observed in patients treated with Pretomanid in combination with bedaquiline and linezolid included damage to the nerves (peripheral neuropathy), acne, anemia, nausea, vomiting, headache, increased liver enzymes, indigestion (dyspepsia), rash, increased pancreatic enzymes (hyperamylasemia), visual impairment, low blood sugar (hypoglycemia), and diarrhea.
Pretomanid, was developed by the nonprofit group TB Alliance. “We can have a huge impact on the lives of people who are afflicted and also take a major step ultimately toward, really, the eradication of a disease like TB,” said Mel Spigelman, president and chief executive of TB Alliance.
Pretomanid is the first tuberculosis medication to be developed by a nonprofit organization. In addition to the United States, TB Alliance filed for approval of pretomanid in the European Union. TB Alliance hopes FDA’s approval will enable other countries, such as China, India and South Africa, to okay the drug and to make it available to their residents.
“The threat of antimicrobial-resistant infections is a key challenge we face as a public health agency,” said FDA Principal Deputy Commissioner Amy Abernethy, M.D., Ph.D.
“The bacterium that causes tuberculosis can develop resistance to the antibiotics used to treat it. Multidrug-resistant TB and extensively drug-resistant TB are public health threats due to limited treatment options. New treatments are important to meet patient national and global health needs. That’s why, among our other efforts to address antimicrobial resistance, we’re focused on facilitating the development of safe and effective new treatments to give patients more options to fight life-threatening infections.”