https://www.epo.org/en/node/koen-andries-jerome-guillemont-imre-csoka

Koen Andries, Jérôme Guillemont, Imre Csoka, Laurence F.F. Marconnet-Decrane, Frank C. Odds, Jozef F.E. Van Gestel, Marc Venet, Daniel Vernier

Drug against multidrug-resistant tuberculosis

Belgium

Winners of the European Inventor Award 2014 in the category industry

The invention is a chemical compound initially labelled “R207910”, later renamed “bedaquiline”. As a so-called first-line therapy for tuberculosis, the molecule proves a highly effective inhibitor of mycobacterial growth in the disease-causing organisms. Bedaquiline also eradicates multidrug-resistant TB (MDR-TB), of which there were a reported 500 000 new cases worldwide in 2012.

All previous TB medications relied on slowing the reproduction of the TB bacteria, thereby gradually bringing down infection levels over time. But as the first truly new anti-TB drug in 40 years, bedaquiline paralyses the energy supply in the bacterial cell, which then dies. This novel mechanism, paired with its fast-acting effectiveness, makes bedaquiline a powerful weapon against “multi-drug-resistant” (MDR) cases of TB.

Societal benefit

The rise of TB infections continues worldwide, with 8.6 million new cases and 1.3 million deaths in 2012, about 95% of them in developing countries. Although conventional drugs are available, many patients stop taking them after initial symptoms of TB subside. But finishing the course of treatment is crucial because drug-resistance and relapses may occur. The new drug reduces treatment time by about 40 days, so patients are much more likely to take it for the full duration of the treatment.

Economic benefit

Next to the direct impact of deaths related to tuberculosis, the disease can have a paralysing effect on the economy of entire regions. Especially in areas where tuberculosis is widespread – primarily in poorer countries – the infection can also be devastating to overall economic performance, because victims are hindered in their ability to work or need to drop out of the workforce entirely as the condition worsens.

Developing countries could lose as much as to US $3 trillion in productivity over the next decade, according to the Global Alliance for TB Drug Development. With current medications, simple infections are treatable in about six months, while up to 20 months can be required for serious cases. The new drug invented by Koen Andries and team, marketed under the name Sirturo, is nearly twice as effective as traditional treatment at eradicating TB in patients – and cures the disease after just eight weeks.

How it works:

While the drugs typically used to treat TB and MDR-TB target either the cell wall or RNA of mycobacterium tuberculosis to slow its reproduction, bedaquiline is the first drug to interfere with its metabolism. Specifically, bedaquiline targets the enzyme ATP synthase (adenosine 5’-triphosphate), which is critical to the energy generation of the mycobacteria.

By interrupting the energy cycle inside the TB bacteria, this "ATP Synthase Inhibitor" can destroy the infectious agent more quickly. And because it is not related to the drugs to which TB is becoming resistant, bedaquiline is also more effective in the destruction of MDR-TB.

The inventor

Koen Andries is a microbiologist with a PhD in veterinary medicine. He began his career with research on viral diseases in animals. After reading a World Health Organisation (WHO) report in 2001 that described the increasing prevalence of tuberculosis as well as its growing unpredictability, he decided to switch his focus to human medicine and began to search for a cure for tuberculosis together with French chemist Jérôme Guillemont.

As a professor emeritus at the University of Antwerp, Andries poured over the “compound library” of his employer Janssen Pharmaceutica, headquartered in Beerse, in the Flemish region of Belgium, together with his team. They tested thousands of chemical substances – repeatedly recombining and retesting them – until they finally zoomed in on the quinoline molecule, which became the basis for their new medication.

Did you know?

The approval of new drugs is a highly bureaucratic process that can take many years. But because of the revolutionary effectiveness of bedaquiline, the US Food and Drug Administration (FDA) accelerated the approval in 2013. Other countries including Germany have also fast-tracked approvals: This is an exceptional status that demonstrates the drug’s importance in battling tuberculosis on a global scale.