How Pembrolizumab Became Oncology’s Closest Thing to a “Silver Bullet”
Are genius molecules a product of nature or nurture?
How you spend your CI budget is as important as how much you are spending; therefore, it is vital to assess the upfront value associated with each potential project in order to ensure your money goes where it should and that the management team is happy.
- October 19, 2020



Kevin Baruzzi, Dr. Arun R. Shrivats and Daria Andreeva
Among the available cancer treatments, pembrolizumab is an industry bellwether: A drug that is as close to a “silver bullet” as the industry has ever had in history. Here are some of the facts about pembrolizumab that have given it a hero status among oncology patients worldwide:

Pembrolizumab has opened up new paradigms in oncology treatment, including a shift toward a molecule-based paradigm (TMB, MSI-H) from a tumor biology-based paradigm. It has also successfully led the charge on a precision, biomarker-based approach to immunotherapy, which has been the province of targeted therapies until now.
Projections suggest pembrolizumab is clearly still an ascendant product: Its sales in 2019 were $12 billion, with analysts estimating this figure will reach $22 billion by 2025.
When a game-changing drug such as pembrolizumab appears on the horizon, one must be intellectually curious and ask how it came into being.
Was pembrolizumab a special molecule – a find of nature – that heralded, perhaps via the minutest alteration, an immunotherapy breakthrough, a chemistry miracle?
Or was pembrolizumab a talent that fell into the right hands and was housed in labs where scientists knew exactly how to nurture it?
To layman eyes viewing the image below, the temptation may be to see the remarkable similarity between pembrolizumab nivolumab (BMS’ compound) and say “nature”.

Like all genius successes, this brings us to a critical ingredient: The way pembrolizumab has been nurtured, and the credit here goes to Merck, perhaps even more so to Merck Research Labs (MRL). MRL-led studies have defied industry expectations on probabilistic success and failure.


Are there learnings here for pharmaceutical companies in general? The answer is a resounding yes.
Every major pharmaceutical company faces the breakthrough imperative, and perhaps the lesson here is that breakthrough drugs are not only born but are also made. More importantly, is there a repeatable model? The answer to this is more complex.
Yes, Merck has demonstrated a repeatable model when it comes to indication and tumor approvals, gaining them at a fast clip and improving success rates. At the same time, even Merck has not shown that there would be a second pembrolizumab in the portfolio just yet, or probably ever. This speaks to an essential truism in biopharma today, specifically that pharma-standard drug assets may be born anywhere, driven by serendipity and effort and best nurtured and cultivated in high-performing development organizations that sit within Big Pharma.
There has been talk in the past on decoupling what Big Pharma do well, namely commercializing drugs from innovation, for which it has an uneven track record. While it may be true that commercialization requires effort and scale that is unavailable to biotech labs, the reality is that the commercial engine is increasingly becoming the table stake; it is not the source of the greatest value add from pharmaceutical companies, and certainly not what differentiates a good Big Pharma partner from a great one. The differentiation and disproportionate value from Big Pharma comes from the confidence and greater chance for success that it can offer to clinical development options available to an asset.
The cumulative experience of large development teams can help steer indication and trial design choices toward successes with a higher probability. One may dare say that it took an MRL to nurture pembrolizumab into a mega blockbuster. Nurturing is key to achieving that full potential that resides in every pharmaceutical asset, and one need not look any further than pembrolizumab to find compelling evidence!
This blog post is a retrospective example of pembrolizumab’s success, but what does the future hold?