March 22, 2019 / All Stories

Tackling Tuberculosis, the World’s Deadliest Infectious Disease

An ancient disease like tuberculosis needs a modern approach. AbbVie process chemists are up to the task.

AbbVie’s Yi-Yin Ku and her process chemistry team are working to tackle tuberculosis.

A Global Health Emergency with Ancient Roots

It was known as consumption, the white plague or, during the Middle Ages in France and England, “king’s evil.” This disease, with ancient origins and the ability to spread quickly through families and entire communities, was often a death sentence.
 
Today, what we now call tuberculosis (TB) remains the world’s deadliest infectious disease. Although fewer people fell ill and died from tuberculosis, the disease is still responsible for 1.6 million deaths globally in 2017 alone, according to the World Health Organization (WHO). Treatments exist, but they aren’t designed for modern times, and multidrug-resistant TB is on the rise.
 
Finding new, accessible and affordable treatments is the focus of groups like the nonprofit TB Alliance and the TB Drug Accelerator (TBDA) consortium, of which both AbbVie and the Alliance are members.
 
Now, these groups are one step closer to realizing this mission, with help from an AbbVie lead scientist and her group, whose chemistry inside the lab and as a team has led to the development of a way to create chemical compounds for TB.

Yi-Yin Ku, Ph.D., has leaned on her 30 years in process R&D to contribute to tuberculosis research.

Challenges with Existing TB Treatments

Before we discover, develop and deliver new medicines to those who need them, we first need to understand why existing treatments are not sufficient, says Chris Cooper, Ph.D., senior director, chemistry, TB Alliance. Education is also an important charge of the Alliance, with misconceptions existing among the highest-risk populations about how TB is transmitted and treated.

The leading current treatment for TB includes a regimen of four medications, dating back to the early 1950s, Cooper says. But there are some who do not respond to first-line treatment, making treatment more challenging. Considered a public health emergency by WHO, an estimated 558,000 people developed multidrug-resistant TB in 2017 alone.
 
Drug-resistant TB typically requires an 18-24 month treatment regimen. Many people, especially in developing countries within Africa and Asia where TB is most prominent, take the medication for a few weeks until they start to feel better. Then, they prematurely stop their treatment, often returning to work quickly out of necessity, Cooper says.

But stopping medication for a bacterial infection breeds drug resistance.
 
“This is the human part of the disease, the reality and why we’re working so aggressively at shorter therapies so you can get full patient compliance,” Cooper says. “Multidrug-resistant TB is on the rise, and this now becomes a problem for high-income countries in addition to the developing world.”
 

'There’s a Great Need'

After 10 years of volunteering her time to support various neglected disease efforts on top of her day job at AbbVie, Yi-Yin Ku, Ph.D., senior research fellow, got the opportunity to use her chemistry expertise to advance tuberculosis research.
 
Her 30-year career in process R&D, first at Abbott Laboratories and now at AbbVie, has allowed Ku to build an expertise in synthetic chemical processes for the manufacture of drug substances. (Translation: Creating cost-effective synthetic processes using inexpensive and readily available raw materials.)
 
It was this expertise that brought Ku into an initiative led by Dale Kempf, Ph.D., distinguished research fellow, AbbVie and a member of TB Alliance’s Scientific Advisory Committee.
 
Kempf had learned of a new anti-TB compound identified and being developed by the TB Alliance. But there was a problem: The Alliance lacked an economical manufacturing method, or series of sequential chemical reactions, to build the compound. Without an efficient synthetic manufacture process, the high cost of goods would pose a significant affordability challenge if the compound were to advance through clinical studies.
 
That was all Ku needed to hear – she was ready to help.
 
“Neglected diseases affect billions of people worldwide and many treatments are not effective, yet the funding is limited,” she says. “There’s a great need to develop affordable medicines. I can’t think of a better way to give back than doing this.”
 
Three of her team members volunteered to help – scientists Alan Christensen, Westin Morrill and Heng Chen – joining the effort to overcome this challenge.  

Yi-Yin Ku (second from left), along with scientists Westin Morrill, Heng Chen and Alan Christensen, worked together to create a new synthesis model to further research for tuberculosis treatment.

'It’s What They’re Good At'

On paper, an alternate approach sketched out by Ku made sense. Start with lower-cost and readily available raw materials and use more effective chemical transformations to build the molecule.
 
But would it work in a lab setting? Ku and her team put the new synthesis model to the test, working outside their normal hours to eventually demonstrate the new process successfully.
 
The results of the new synthesis were encouraging. The cost of one key ingredient was reduced by more than sevenfold, and the overall yield – the product obtained – was increased by more than four times.

It was not fancy equipment or rare ingredients that led to the team’s new synthetic process. Instead, it was a thoughtful approach and the willingness to break down a process and find ways to improve it, Kempf says.
 
“This team’s expertise is in identifying the best building blocks and the best ways to put them all together – it’s what they’re good at,” he says.
 
Ku and her team assembled a technical document that will help other researchers apply the new process, a key element of the collaboration with TB Alliance. This chemical process is now available to be used as the new compound is advanced through clinical trials.
 

An Ongoing Commitment to Neglected Diseases

AbbVie’s work in tuberculosis is part of a broader pro bono research program through which the company’s scientists donate their time to improve global health.
 
Learn more: Two AbbVie scientists left retirement behind to help people suffering from a neglected tropical disease
 
Participation has grown to more than 400 researchers who gave nearly 40,000 hours in 2018 toward developing treatments and technologies for tuberculosis, malaria and neglected tropical diseases (NTDs) including river blindness, elephantiasis, Chagas disease and dengue fever.
 
Contributions from AbbVie have made a critical difference for TBDA and TB Alliance efforts, Cooper says.
 
“AbbVie is doing great science for the sake of those most afflicted,” Cooper says. “Tuberculosis is an infectious disease where most of the patients live well below the poverty line, and this work impacting the cost of goods could really revolutionize what we’re doing here.” 

References

  1. World Health Organization. WHO calls for urgent action to end TB. Accessed March 19, 2019. Available: https://www.who.int/news-room/detail/18-09-2018-who-calls-for-urgent-action-to-end-tb-.
  2. World Health Organization. Tuberculosis: Key facts. Accessed March 19, 2019. Available: https://www.who.int/en/news-room/fact-sheets/detail/tuberculosis.
  3. World Health Organization. Global tuberculosis report 2018. Accessed March 19, 2019. Available: https://www.who.int/tb/publications/global_report/en/.
  4. Kim, Jim Yong; Shakow, Aaron; Castro, Arachu; Vande, Chris; Farmer, Paul. Tuberculosis control. Global Health Public Goods for Health – a reading companion. Accessed via World Health Organization website, March 19, 2019. Available: https://www.who.int/trade/distance_learning/gpgh/gpgh3/en/index5.html.
  5. TB Alliance. The Pandemic. Accessed March 19, 2019. Available: https://www.tballiance.org/why-new-tb-drugs/global-pandemic.



Media inquiries

Mary Kathryn Steel
Email: mk.steel@abbvie.com
Call: + 1 847-937-4111

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