A small medicine, a big step for the treatment of tuberculosis



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The infectious disease that alone kills the greatest number of humans on an annual basis today, in 2019, is tuberculosis (TB). This fact may surprise many people who think about TB only in conjunction with the famous consumers of artistic works such as Mimi of La Boehme, Violetta of La Traviata or Hans Castrop of The Magic Mountain.

Fortunately, the number of TB cases in the United States is at its lowest historical level: fewer than 10,000 cases a year. About one-third of the world's population is infected with tuberculosis bacteria. In 2017, about 1.6 million people died of tuberculosis.

Existing TB cases are sometimes very difficult to treat. This challenge, which is synergistic with all the other difficulties of TB treatment (such as multiple treatment regimens, social status, co-infection with HIV), is antibiotic resistance. Tuberculosis is a bacterial infection and, like any bacterial infection, the threat of antimicrobial resistance is high.

Tuberculosis resistance can be a single drug or multiple drugs. The latter, when it concerns two anti-tuberculosis drugs, is called multidrug-resistant tuberculosis (MDR-TB) and represents about 3.7% of new cases.

The MDR-TB class includes a subgroup of highly drug-resistant tuberculosis (XDR-TB). There is no good treatment regimen to treat this infection and those that exist are toxic, extremely cumbersome in terms of pills and require intravenous treatment. And the extended XDR-TB is often a death sentence.

Revolution in the treatment of tuberculosis UR

In this context, it is easier to understand why a new drug approval was making headlines around the world when a new antibiotic against tuberculosis was approved by the Food and Drug Administration (FDA). The drug is called pretomanid and it will be used in combination with two other previously approved drugs (bedaquiline and linezolid in the so-called BPaL regimen) in the treatment of drug-resistant TB.

The Nix-TB clinical trial that led to its approval included 109 patients with XDR or MDR-TB and included a 6-month course of treatment. Although there is no control group in this trial – an important limitation to keep in mind – a revolutionary cure rate of 89% has been achieved. This rate of 89% was achieved with 3 drugs over 6 months, while the dismal cure rates of 34% were the same as those obtained with the historical treatment regimen of drugs aged 6 to 8 months. This type of result is extraordinary.

New ways and incentives for anti-infectives

The approval, based on the extremely encouraging results of the clinical trial, is important not only because it recognizes and facilitates the treatment pathway for what was arguably the most difficult infectious disease to treat. It is also important because its approval has taken advantage of some of the important new FDA pathways and incentives created under the 21st Century Treatment Act, in recognition of the fact that antimicrobial resistance and disease Infectious diseases in general are unique in biotechnology, pharmaceutical and health.

Antibiotics must be used judiciously through proactive management to maintain their maximum effectiveness against resistance. Since they are relatively inexpensive and taken for a set period of time, they are not major producers.

The returns on investment, after a $ 1 billion drug development cost, are not attractive, hence the departure of pharmaceutical companies to move away from antibiotics and the threat of bankruptcy among those that remain . Claiming this reality, pretomanid was uniquely developed by a non-profit entity, TB Alliance.

The approval of Pretomanid is an important step as it illustrates the cumulative effect of the many systems in place to encourage the development of measures to control infectious diseases. Pretomanid was the subject of an accelerated priority review and was approved with the help of a modified criterion called Limited Population Path (LPAD).

Because it targets a small population of patients with few options available, this pathway allows for smaller and shorter clinical trials than would otherwise be the case. It has also been designated as a Qualified Product for Infectious Diseases (PDID), which increases the market exclusivity period before generic versions can be licensed.

Incentives for orphan drugs have also been applied. Pretomanid also earned a priority examination voucher for tropical medicine, which can be sold at a very lucrative price to another pharmaceutical company, allowing the FDA to quickly review a different product. Hopefully, other infectious disease products will also be able to navigate successfully through these myriad programs.

As with every new diagnostic test for antimicrobial, vaccine or infectious disease, I celebrate the development of pretomanid as a major technological advance that enhances humanity's resilience to ever-present infectious disease threats. The advent of a real option to treat one of the most lethal forms of the leading killer of infectious diseases is a great example of the power of the human spirit. What was an insoluble problem now has an elegant and relatively simple solution.

Dr. Amesh Adalja, graduate of the Board of Directors in Infectious Diseases, Critical Care Medicine, Emergency Medicine and Internal Medicine. He is a senior scientist at the Johns Hopkins Center for Sanitary Security. Follow him on Twitter: @AmeshAA.

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