Deadly Tuberculosis Cure On The Way

In a landmark decision, the Food and Drugs Administration (FDA) approved a new oral three-drug regimen on August 14 to treat drug resistant tuberculosis. Comprising of bedaquiline, linezolid and the novel compound pretomanid, the rigorous new regimen is together called BPaL. The regimen was developed to help patients fight non-responsive Multidrug-Resistant TB (MDR-TB) and Extensively Drug Resistant TB (XDR-TB) prevalent in huge numbers globally. 

Developing new treatment is the need of the hour since tuberculosis is the leading cause of death worldwide from a single infectious agent, surpassing HIV/AIDS, according to the World Health Organization (WHO).   

The scientific advancement was executed by the New York-based nonprofit organization, The Global Alliance for TB Drug Development (TB Alliance), to whom the FDA granted approval. The FDA reviewed the pretomanid tablets on priority in a shortened time period by placing it under the category of Orphan Drugs which receives special attention in times of crisis. If necessary, the FDA sometimes provides financial assistance to pharmaceutical companies to develop new drugs listed under Orphan Drugs to treat rare diseases. 

The United States Congress set up the Limited Population Pathway for Antibacterial and Antifungal Drugs under the aegis of the 21st Century Cures Act. This was done to provide expedited approval for drugs that could treat life-threatening infections within a small population of patients lacking access to healthcare. So far, pretomanid is the second drug to be approved under the pathway, according to the press release issued by the FDA. 

This medical discovery provides hope to millions of people globally diagnosed every year since the drug will be made available in high income markets as well as non-exclusive middle-income and low-income countries. The nonprofit TB Alliance gave the license to global pharmaceutical company Mylan NV to both manufacture and sell pretomanid tablets. They hope to get the medication out in the market by the end of the year. The organization has already approached the European Medicines Agency (EMA) for the official approval of BPaL, Reuters reported Thursday. 

Global Statistics

Only 25 percent of the estimated 558,000 people who developed Multi-Drug Resistant TB (MDR-TB) and Rifampicin-Drug Resistant TB (RR-TB) in 2017 received the second-line regimen. According to the Global Tuberculosis Report 2018, the success rate of the treatment was low at just 55 percent for MDR-TB and 34 percent for XDR-TB globally. India and China make up for 40 percent of the global gap in treatment and detection. 

The number of MDR/RR-TB cases detected and notified worldwide rose from 153,119 in 2016 to 160,684 in 2017. However, there has been some progress since Bangladesh, Ethiopia, Kazakhstan, Myanmar and Vietnam are some of the countries with a success rate of above 70 percent. 

Tuberculosis drugs A patient suffering from Tuberculosis rests inside a hospital in Agartala, March 24, 2009. Reuters/Jayanta Dey/Files

South Africa Study

The FDA’s approval of the drugs was based on testing its efficacy on patients based in South Africa at three sites. The Nix-TB is the first clinical trial to assess the impact of a new drug regimen on patients with XDR-TB and non-responsive MDR-TB. Using only pills and no injections, the study included 109 people in total, starting from the age of 14 to those infected with HIV. They were provided treatment for six to nine months as opposed to 18 to 24 months needed by the previous treatment regimens. 

Shorter, more effective and less invasive treatment for XDR-TB was explored in these patients who were monitored for two years in case of relapsing after receiving treatment from 2015 to 2017. The success rate was at 91 percent for the Nix-TB trial patients.

The study was conducted in partnership with Janssen Pharmaceuticals, the company that discovered bedaquiline and TB Alliance. Prior to the FDA’s approval, the agency had also compared the three-drug regimen against 19 other clinical trials conducted in 14 countries and 1,168 patients. 

Side Effects

According to the press release issued by the FDA, the side effects of taking pretomanid tablets include “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.”

Even patients who display sensitivity to the other drugs in the regimen (bedaquiline and linezolid ) should avoid it. The safety of the drug is yet to be determined for pregnant women and children.