Roche’s lifesaving legacy in antibiotic innovation

As a young scientist in 1978, Urs Schaad was driven to find the best - and safest - antibiotic to help save the lives of critically ill infants and young children. His studies led him to a collaboration with Roche and the development of their antibiotic which has since saved millions of lives, young and old. 

Fast forward more than 45 years to today. Infectious disease discovery scientists at Roche Pharma Research and Early Development (pRED), led by Ken Bradley, are advancing the company’s legacy in antibiotic innovation with the discovery of what could be the world's first new class of antibiotics in more than 50 years.

The two scientists sat down recently at Roche headquarters in Basel, Switzerland, to talk about the urgent need for a new class of antibiotics to save more lives globally. They compared what has changed in antibiotic discovery in the past 45 years, and what remains the same.

“When you were first looking at the compound in the early days did you have an inkling that this looked like a molecule that could be something special?” Ken asked Urs about the medicine that hit the market in the 1980s and remains one of the most commonly used antibiotics today.  

“There was a lot of evidence in favour of the potential treatment and it was clear that we needed this compound for very sick children,” replied Urs, who was Medical Director and Professor of Paediatrics at the University Children’s Hospital in Basel and helped lead the drug research and development. “It was important for me to conduct these studies to show the benefits in children, to know how this drug would work in little patients.”

Much has changed since the golden age of antibiotic development in the 1940s, 50s, and ‘60s, when new natural product-based antibiotics were often discovered and new drugs came to market frequently. Developing potential new medicines today is an intense scientific journey, starting by identifying effective molecules, and then trying to understand their structure and how they work. It is also critical to ensure safety by reducing toxicity for patients. 

Both scientists agreed that finding new ways to kill bacteria is more important than ever in the fight against antimicrobial resistance, or AMR. Known as a silent pandemic, AMR occurs when bacteria and other pathogens evolve to resist the effects of medications designed to kill them.   More than 39 million people are expected to die from antibiotic-resistant infections between now and 2050, according to a report published in the journal The Lancet. 

“The new Roche antibiotic currently in clinical studies has shown that it can kill a specific bacterium that has been classified by the World Health Organization and the U.S. Centers for Disease Control as the top priority urgent threat, as it has become incredibly drug-resistant,” Ken shared with Urs. “In some parts of the world, 80 percent of the population of this potentially deadly bacteria - Acinetobacter baumannii - have become resistant to last-line antibiotics. These are usually the last treatment options for patients infected with bacteria that are resistant to other available antibiotics.” The bacteria is primarily found in hospital settings.  

“With this existing pandemic of antimicrobial resistance there is hope that this and maybe more new compounds will help to fight it, but it will still be with us a long time,” Urs said. 

Ken agreed. “Bacteria will always evolve resistance under the selective pressure of any new compound we bring forward. So we need to have that mentality that we are not done. We will always need new solutions as the bacteria evolve to become resistant. We can slow that down through stewardship programs - identifying the right patients that need that drug, and avoiding overuse.” 

While new technologies such as machine learning and artificial intelligence are supporting discovery, nothing can replace dedicated scientists.

Collaboration between the diagnostics and pharmaceutical divisions at Roche has been crucial, along with academic partnerships, Ken said. In this case, Roche has worked closely with Harvard University to better understand the targeted bacteria physiology and how it can be killed.

“Because of the economic challenges of bringing new antibiotics forward there are not a lot of large pharmaceutical companies left in this space,” Ken continued.

For Urs, now in well-deserved retirement, the influence of his work and Roche's enduring commitment gives hope for continued progress in combating infectious diseases.

“We have saved millions of lives with antibiotics and the potential that this can go on with these new drugs is huge. I believe it will happen.”