“Patent thickets” and mergers cushion the fall.

For clarity, sales at risk refers to a product’s annual revenue in the year before loss of exclusivity. Actual or predicted loss is the difference between that sales at risk number and the first full year of sales post expiry, as reported by companies for historic expiries or computed by Evaluate Pharma’s consensus for those still to happen.

The historic numbers in this analysis show that sales never drop as precipitously as these at-risk estimates suggest. Even small molecules, which see revenues disappear much more rapidly than biologicals, do not immediately drop to zero when copycats arrive.

But it is clear that there is a lot at stake for biopharma in the coming years, even if the real rate of erosion is unknown.

Burning questions

Companies and investors are keen to know how quickly a major source of income will be lost, but in reality this is very hard to estimate, particularly for biologicals. The burning question on Abbvie’s recent earnings call was what Humira might sell in 2023, but opinions range widely, despite the close scrutiny.

The sellside is pencilling in US sales of $10.9bn in 2023, according to Evaluate Pharma, while the company has issued guidance in the $8.4-12.0bn range.

Another variable for expiries further out is the exact date of patent loss. Many of the products highlighted here are still being litigated, so could end up with longer life spans.

But these products will fall eventually. And what do large developers do when confronted with a revenue gap? They make acquisitions. This approaching wave of expiries is already being cited by those keen to see an uptick in M&A, and in many ways the need to replace sales provides a more convincing motivation for dealmaking than tumbling biotech valuations.

All of those named below will be feeling the pressure, in particular Bristol Myers Squibb and Abbvie, which appear more than once in the top 10. The likes of Merck & Co and Regeneron, meanwhile, face the loss of products that dominate their revenue streams.

The impending fall of these mega-blockbusters will be music to the ears of those advocating lower drug costs, of course. But developers will not give up without a fight, and it will require a significant strengthening of political will to weaken industry's ability to weave the so-called patent thickets that protect these huge franchises. For now, it feels much more likely that these patents will get extended rather than falling unexpectedly.