Why FDA Approval Isn't the Moment Biosimilars Start Competing

Amgen got FDA approval for Amjevita - the first Humira biosimilar - in September 2016. Amgen shipped its first US vial in January 2023.

Six and a half years between approval and market entry, on a drug that was already developed, already manufactured, already tested.

Nine more Humira biosimilars followed the same pattern. FDA approved them one by one between 2016 and 2022. They all launched in the same narrow window in 2023. The full list, with approval dates and years shelved, is below.

The gap between "approved" and "on sale" isn't a quirk of Humira - it's how biologics competition works. Once you see the mechanism, you can predict exactly where it will happen next (14 biosimilars are in exactly that position right now).

How the gap gets built

Humira's original US compound patent - US 6,090,382, "Human antibodies that bind human TNFα" - expired December 31, 2016.

Under the simplest model of patent protection, biosimilar competition could have begun in Q1 2017. Amgen's September 2016 approval was timed for exactly that window.

But a drug's compound patent is only one piece of its legal protection. AbbVie had filed more than 300 US patent applications on Humira, with 165 granted as of 2023.

The portfolio covered specific formulations, pre-filled syringe devices, dosing methods for individual indications, manufacturing processes, and cell culture media. It's one of the largest patent portfolios ever built around a single biologic.

Individually, many of the secondary patents were narrow and defensible-around. Collectively, they created a legal surface area that was faster to negotiate than to litigate.

One subtlety to understand before the negotiation story makes sense: developing and filing for FDA approval is itself not a patent issue.

Under 35 U.S.C. §271(e)(1), the Bolar safe harbor, any activity reasonably related to FDA approval is explicitly exempt from patent infringement.

Amgen could develop Amjevita, run trials, manufacture process-qualification batches, file its BLA, and receive FDA approval, all without infringing AbbVie's patents. The patents only come into play at commercial sale.

Why negotiation, not litigation

Because development is non-infringing and commercial sale is infringing, the biosimilar maker's real decision doesn't arrive until the launch stage.

At that point, the maker has a real choice: fight each patent claim in court, or settle with the reference product holder on launch terms. Both are legal. Both are normal.

The mechanics favor settlement, and the math is worth walking through.

An at-risk launch - selling while patent disputes are still pending - exposes the seller to treble damages under 35 U.S.C. §284.

On a drug with $15-20 billion in annual US sales, treble damages on even a year of at-risk revenue could run into tens of billions in liability. For a biosimilar maker with a few hundred million in development costs, that's an asymmetric trade: the upside of winning is saving years of waiting, the downside of losing is existential.

There's a second, less-discussed factor.

The Biologics Price Competition and Innovation Act deliberately does not grant a 180-day first-filer exclusivity to biosimilars that successfully challenge reference-product patents.

Unlike generics, a biosimilar maker who invalidates an originator's portfolio gets the same launch window as every competitor who did nothing. The economic incentive to fight patents is low; the economic incentive to settle quickly on favorable terms is high.

This is why ten Humira biosimilars launched in the same narrow 2023 window. Every biosimilar maker reached a separate agreement with AbbVie; the aggregate outcome looks coordinated because the individual math was the same for everyone.

While they waited: Europe

Biosimilar makers didn't sit on their hands during the US wait.

The EU compound patent on Humira expired in October 2018 - more than four years before the US launch window opened.

EU patent law is less forgiving of secondary patents, so AbbVie didn't have the same layered portfolio to negotiate against in Europe. Three Humira biosimilars launched in the EU on the same day in October 2018: Amgevita (Amgen), Imraldi (Biogen/Samsung Bioepis), and Hyrimoz (Sandoz).

Same drug, same factories, different label. Amgen sold Amjevita in Europe under the brand name Amgevita starting in 2018 - five years before it was legally allowed to ship the same drug in the US.

Economically, this softened the US wait substantially. Biosimilar makers were earning real revenue in Europe while their US inventory sat idle. The "shelved" years in the US weren't zero-revenue years for the overall program - they were ex-US revenue years with a parked US launch on the horizon.

This pattern - EU cliff arrives years before US cliff - is typical for biologics with layered patent portfolios. For anyone modeling future cliffs, EU erosion is usually a reliable leading indicator of US timing. Humira's transatlantic delta was 4.3 years. Other biologics have run larger.

The commercial market moved fast

Three years after the US biosimilar launch window opened, Humira's global revenue was down nearly 80% from peak.

FY 2022 global Humira revenue was $21.24 billion - AbbVie's highest-ever annual sales on the drug, and the last full year before US biosimilars entered the market. By FY 2024 the same drug generated $8.99 billion globally - a 58% decline in two years. FY 2025 came in at $4.54 billion, a 79% drop from the 2022 peak.

The mechanism - patent expiry allowing settled biosimilars to launch - played out on the timeline the patents themselves had signaled years in advance.

That's the commercial market story. It matches what industry models predict: cliff dates are public, biosimilar entries are public, erosion curves are well-studied.

The Medicare market didn't

Here's the part I find more interesting, because it doesn't match the commercial story.

In 2024 - the second year of US biosimilar availability - Humira Medicare Part D spending was $5.72 billion. All 35 Humira biosimilar SKUs combined totaled approximately $162 million in the same program. Biosimilar share of Medicare Part D adalimumab spending in 2024: 2.8%.

Global commercial Humira revenue dropped about 58% between 2022 and 2024. Medicare Part D Humira spending rose about 5% over the same window. Two curves measuring the same drug, in the same country, moving in opposite directions.

The mechanism behind the lag is nuanced, and a full explanation requires expertise in Medicare Part D contracting that I don't have. The factors most commonly cited: Humira historically commanded some of the largest manufacturer rebates in Part D, and biosimilars priced lower from launch have less room to offer competing rebate deals that would make plans switch.

Multi-year formulary contracts, continuity-of-care rules on biologic switching, and patient-level cost-sharing dynamics all add friction on top. The result is a Medicare Part D market that's responding to biosimilar competition on a different - slower - timeline than the commercial market.

How much of the current lag is structural versus transitional - as the 2024-2025 Inflation Reduction Act reforms reshape Part D pricing - is a genuinely open question.

For anyone building a post-cliff revenue model on a biologic franchise, this matters. Commercial and Medicare are two different curves, and if your model uses one for both, it's almost certainly overstating erosion on the Medicare side. It's a recoverable signal - worth modeling separately.

The pattern

Approvals are lagging indicators.

Patent cliffs are the event.

The gap between them is the part that matters - and it's not a historical quirk of Humira. Fourteen biosimilars sit today in exactly the same position Amjevita sat in 2017: FDA-approved, legally unsellable in the US, waiting for the patent cliff to arrive.

The longest-waiting one has been in that position since August 2016, and its reference product's US patent cliff isn't scheduled until April 2029. That's roughly double the Amjevita wait, on a drug whose story unfolded through head-on litigation rather than settlement. That story is here.