The fall of Β-lactam R&D
In the 1980’s there must have been >1,000 scientists, including chemists, microbiologists, pharmacologists etc, working in the field of Β-lactam R&D in major Pharma like Beecham, Bristol Myers Sqibb, Dainippon Sumitomo Pharma, Eli Lilly, Merck, Pfizer and Roche. I’m sure this is not a complete list, but the point is that there were many teams of >100 people working on antibiotic R&D in most large Pharma companies. They delivered generations of antibiotics including penicillins, cephalosporins, carbapenems and monobactams.
Antibiotic resistance was a concern with each generation of compounds overcoming serine lactamase resistance of the time. Scientists were also tasked with altering the spectrum of the antibiotics to capture the infections of their time and to improve the pharmacology to create products that could be dosed less frequently to create a marketing advantage.
It became difficult to create a breakthrough differentiated product in this landscape, especially Β-lactam’s that could be dosed once or twice a day, and so return on investment into these large teams fell. Mergers created unsustainably large antibiotic capabilities and led to redundancies.
By the 1990’s critical mass of Β-lactam R&D had collapsed.
Many of the breakthroughs in recent years may have their foundations in the people and expertise from the 1980’s including ceftobiprole, avibactam and cefiderocol.
A key question we should all ask is whether Β-lactam R&D is complete and finished or whether the new challenges of resistance and spectrum and much less concern around dosage regimens lead to new opportunities for continued Β-lactam discovery and development.
I would really like to encourage a discussion, including those with the deep experience from the 70s, 80s and 90s, with the new generation of researchers, around what might be worth investigating to ensure that no Β-lactam “stone” is left unturned in the search for new generations of antibiotics – they may not be hugely innovative, but they might be useful!
What new chemistry is available to be deployed? What avenues merit further investigation?
At the very least, we could create a foundation of knowledge for future generations to make sure that the Β-lactam class is truly exhausted before we give up on it!
Over the coming months I will be adding to this blog with points for discussion. Hopefully some will enjoy the musing and perhaps even join in!