"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. This approval also marks the second time a drug is being approved under the Limited Population Pathway for Antibacterial and Antifungal Drugs, a pathway, advanced by Congress, to spur development of drugs targeting infections that lack effective therapies. We hope we continue to see more development of antibacterial drugs for treating serious or life-threatening infections in limited populations of patients with unmet medical needs."
Pretomanid in combination with bedaquiline and linezolid is approved for treating a limited and specific population of adult patients with extensively drug resistant, treatment-intolerant or nonresponsive multidrug resistant pulmonary TB. Multidrug-resistant TB and extensively drug-resistant TB are difficult to treat due to resistance to available therapies. 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 effectiveness 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 extensively drug resistant TB.
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 (transaminases and gamma-glutamyltransferase), indigestion (dyspepsia), rash, increased pancreatic enzymes (hyperamylasemia), visual impairment, low blood sugar (hypoglycemia), and diarrhea.
Pretomanid used in combination with bedaquiline and linezolid should not be used in patients with hypersensitivity to bedaquiline or linezolid.
Pretomanid is the second drug to be approved under the Limited Population Pathway for Antibacterial and Antifungal Drugs, or LPAD pathway, established by Congress under the 21st Century Cures Act to advance development and approval of antibacterial and antifungal drugs to treat serious or life-threatening infections in a limited population of patients with unmet need. Approval under the LPAD pathway may be supported by a streamlined clinical development program. These programs may involve smaller, shorter or fewer clinical trials. As required for drugs approved under the LPAD pathway, labeling for Pretomanid includes certain statements to convey that the drug has been shown to be safe and effective only for use in a limited population.
Pretomanid also received the FDA’s Qualified Infectious Disease Product (QIDP) designation. The QIDP designation is given to antibacterial and antifungal drug products intended to treat serious or life-threatening infections under the Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act.
The FDA granted Pretomanid Tablets Priority Review, under which the FDA’s goal is to take action on an application within an expedited time frame, and Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.
The FDA granted the approval of Pretomanid Tablets to The Global Alliance for TB Drug Development (TB Alliance). With this approval, The Global Alliance for TB Drug Development is awarded a Tropical Disease Priority Review Voucher in accordance with a provision included in the Food and Drug Administration Amendments Act of 2007 that aims to encourage development of new drugs and biological products for the prevention and treatment of certain tropical diseases.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.