Thomas Holbro: Think big!
Published on 20/09/2023
Thomas Holbro was going through one of the most difficult times during his career back in 2017. An important trial in the acute heart failure space he oversaw as part of his work in the Novartis Global Drug Development (GDD) unit had just read out with neutral results and he was tasked to sift through the data to extract some key findings.
It could have all been different. The outcome of the trial had been eagerly awaited and would have given Novartis fresh impetus to extend its leadership position in the cardiology space. But although previous clinical trial data showed the compound to be effective, late-stage tests failed to corroborate the early results.
Late-stage development failures are always hugely disappointing and lead to significant uncertainties for involved teams, possibly with personal and or even larger organizational implications. This time, it was different. Leadership appreciated that failure is part of drug discovery.
“Our leadership made it clear that together with a small team we should wind down the program. But they also told us in advance that they wanted us to stay and take over a new program later,” Holbro told live magazine back in 2018.
This not only took the pressure off Holbro and his colleagues but motivated them to stay alert and gather as much information that would help them for the next trials. This, as leadership had hoped, would also give them the extra motivation to redouble their efforts in future.
It played out exactly in that way – if not better. Holbro moved to lead another program, which now looks to be a potential game changer in several disease indications.
Think big
“As a scientist, I was always guided by facts, and the lesson we learned from the failed cardiovascular trial also helped me during the next clinical tests that I led. Furthermore, gaining the trust from the leadership motivated me to go on.”
The motivational boost came at the right time, as the upcoming program could have hardly been more challenging. Colleagues at the Novartis Institutes for BioMedical Research (NIBR) had developed a new molecule that could be used to interfere in a series of diseases in which the complement system – a part of the human immune system – is misfiring.
Besides the complex biology underlying the complement system as well as the intricate decision about which of the many possible indications to pursue first, the team faced the added challenge of setting up trials in rare disease areas, which are notoriously challenging from both the medical and the commercial point of view. But the team was ready to go full speed and take the risk, as they were fully convinced of the underlying science and the huge patient need.
To gain time and to resolve concerns about potential side effects, colleagues from NIBR and Holbro’s development team connected very early to set up a Phase II study that served as a proof-of-concept test but at the same time answered key questions for further development. The goal was to complete this step immediately and move into late-stage clinical trials – typically referred to as Phase III studies.
This joint team also did another unusual thing. Instead of testing the compound in different disease areas one by one sequentially, they launched several studies in parallel. “The reasons for this move were relatively simple. First, it made scientific and strategic sense, second it was valid from a patient perspective, and third, it was also convincing from a commercial point of view because we were able to create necessary synergies by building what we now call ‘a pipeline in a pill,’” Holbro said.
Also, they were thinking big when it came to late-stage trials. “We designed a head-to-head study against the most efficacious drug in the market and decided to test our drug candidate for superiority,” Holbro explained. “The study would only have a positive outcome if we were able to deliver better results than the current gold standard.”
