Keytruda earned $31.68 billion for Merck in 2025 out of $65.01 billion in total sales [1]. That is 48.7% of company sales (analysis). Merck lists 2028 as the US expiry year for the Keytruda compound patent family [1].
One ratio like this tells a planner more than a list of expiry dates. This article builds a multi-year patent cliff model from documented SEC, CMS, FDA and court data. It then tests the model against five real loss-of-exclusivity (LOE) events.
The Short Answer: What a Patent Cliff Model Needs
A multi-year patent cliff model needs six steps. Build a dated LOE calendar. Measure revenue exposure. Pick an erosion archetype for each product. Add the effect of US price-setting rules. Subtract mitigation. Track the remaining gap against dated triggers.
How big is the 2025-2030 patent cliff?
Evaluate puts the figure above $300 billion for 2025 to 2030. Its page does not state the method behind the number [2].
“Between 2025 and 2030, over $300bn in prescription drug revenues will lose exclusivity.” (Evaluate, October 13, 2025) [2]
William Blair gives a similar figure of more than $300 billion over the next five years, as cited by Reuters on May 1, 2026 [3]. Bernstein analysts estimate that revenue exposed to patent expiry over the next seven years is about 2.5 times the exposure of the prior 16 years [3].
The Nine Findings That Matter
Keytruda was 48.7% of Merck’s 2025 sales ($31,680 million of $65,011 million). The US compound patent family expires in 2028, with two further patents in 2029 [1]. The share is analysis.
Eliquis and Opdivo together were 50.8% of Bristol Myers Squibb (BMS) 2025 revenue ($24,492 million of $48,194 million) [4]. BMS lists US 2028 as the earliest exclusivity date for Opdivo [5]. The share is analysis.
Humira revenue fell 78.6% from $21.2 billion in 2022 to $4.540 billion in 2025 [6] [7]. The percentage is analysis. AbbVie total net revenue still grew 8.6% in 2025 [7].
Skyrizi and Rinvoq earned $25.866 billion in 2025, 1.22 times Humira’s 2022 revenue [7] [6]. The ratio is analysis.
Entresto net sales fell 1% for full-year 2025 but 43% in the fourth quarter [8]. An annual figure hides the exit run-rate.
Revlimid worldwide sales fell 49% in 2025, to $2.951 billion, under US generic licenses that were volume-limited until January 31, 2026 [4] [5].
The first ten Medicare negotiated prices are 38% to 79% below list. The unweighted mean is 63.1% [9]. The mean is analysis.
Keytruda Qlex earned $590 million in the first half of 2026. That is 3.6% of the $16.4 billion Keytruda total [10]. The share is analysis.
FDA lists eight ustekinumab biosimilars approved between October 2023 and May 2025 [11]. The first US launch was on January 1, 2025, under a settlement [12].
What Is a Patent Cliff? Definitions Used in This Model
What does loss of exclusivity (LOE) mean?
LOE is the date after which no patent or regulatory right blocks a generic or biosimilar from the US market. It is a market event, not a legal filing.
Is patent expiry the same as generic entry?
No. Merck states that expiry of the compound patent generally ends market exclusivity. It also states that other patents may give additional market exclusivity [1]. Settlements can move entry earlier or later than expiry. Januvia is an example. Merck states that settlements extend its US exclusivity through May 2026 [1].
Generic vs. biosimilar: which rules apply?
Generics copy small-molecule drugs and follow 21 U.S.C. § 355. Biosimilars copy biologics and follow 42 U.S.C. § 262. For a biologic, the statute bars a biosimilar application for 4 years after first licensure. It bars approval for 12 years [13].
Methodology: Data, Selection Rules, Calculations and Limits
What data did we analyze, and for which period?
We read company annual reports (Form 10-K and Form 20-F) for fiscal 2025, quarterly earnings releases through Merck’s second quarter of 2026, CMS negotiation fact sheets, FDA pages, federal statutes and one court-reporting source for each case. Reported sales cover 2022 to the second quarter of 2026. Forward dates run to 2033.
Which records are included?
A product is included if a company filing states a US or EU expiry date, if a generic or biosimilar has entered, or if CMS has set a negotiated price. A drug is counted once. Eliquis uses the global revenue that BMS reports. The Pfizer share is not added.
How were the calculations made?
Shares are product revenue divided by company revenue for the same year. Declines are one minus the later figure divided by the earlier figure. Where a company reports only a percent change, the prior figure is back-calculated and marked as analysis. Scenario tables multiply a base revenue by a chain of annual retention factors.
What are the limits?
Company revenue is global and net of rebates. US-only figures are not available for several products. The Stelara and Darzalex dollar values come from rounded percentages in the J&J 10-K, so they are approximate [14]. Evaluate’s $300 billion figure uses a method we cannot see. Scenario curves are assumptions.
Patent Timeline: When Do the Big Brands Lose Exclusivity?
Table 1 lists scheduled and settled dates from company filings. Treat each date as the earliest credible entry, not a forecast of entry.
Table 1. LOE calendar for selected brands (status as of company filings for fiscal 2025)
Drug
Company
Active ingredient
2025 revenue
Key LOE dates
Date type
Source
Keytruda
Merck
pembrolizumab
$31.68B (incl. Qlex)
US 2028 (two more patents 2029); EU 2031; Japan 2032-2033; China 2028
Patent expiry
[1] [15]
Eliquis
BMS / Pfizer
apixaban
$14.44B (BMS-reported)
US: settled generics permitted 2028; EU patents and SPCs expire Nov 2026
Settlement; patent expiry
[5] [4]
Opdivo
BMS
nivolumab
$10.05B
US 2028; EU 2030; Japan 2031
BMS minimum exclusivity estimate
[5] [4]
Darzalex / Darzalex Faspro
Johnson & Johnson
daratumumab
About $14.1B (analysis: 15.0% of $94.19B)
US 2029 (two patent families); EU 2031/2032 in select countries
Patent expiry
[14] [16]
Ibrance
Pfizer
palbociclib
Not in sources reviewed
US 2027; EU 2028; Japan 2028
Basic product patent
[17]
Xtandi
Pfizer / Astellas
enzalutamide
Not in sources reviewed
US 2027
Basic product patent
[17]
Lynparza
AstraZeneca / Merck
olaparib
Not in sources reviewed
US 2027; EU 2029
Patent expiry
[1]
Gardasil 9
Merck
HPV vaccine
$5.23B (Gardasil total)
US 2028; EU 2030
Patent expiry
[1] [15]
Keytruda patent expiration: what happens in 2028?
Merck lists 2028 for the US Keytruda compound patent. Two additional patents in the family expire in 2029 because of patent term adjustment [1]. The EU date is 2031 and the Japan date is 2032 to 2033 [1].
What does Merck say about US price-setting for Keytruda?
Merck states that it expects Keytruda to be selected in 2027 for government price setting. It also states that US sales of Keytruda “will decline materially after that time” [1]. The price would take effect January 1, 2029 [1].
Eliquis generic entry: when can apixaban generics launch?
BMS states that the settled generic companies are permitted to launch in 2028, subject to additional challenges [5]. The BMS-Pfizer Alliance stated on September 3, 2021 that the earliest launch date is April 1, 2028 [18]. The Federal Circuit affirmed that the composition-of-matter patent (US 6,967,208) and the formulation patent (US 9,326,945) are valid and infringed [18].
Why do the Pfizer and BMS filings show different years?
Pfizer’s 10-K table lists 2027 for the Eliquis basic product patent, with a footnote [17]. BMS and the Alliance give 2028 as the launch date for settled generics [5] [18]. This model uses 2028, because it is the date tied to a settlement and a court ruling.
Opdivo, Darzalex, Ibrance and Xtandi: what are the dates?
BMS estimates US minimum exclusivity for Opdivo at 2028, EU at 2030 and Japan at 2031 [5]. J&J states that both Darzalex patent families expire in the US in 2029 [14]. Pfizer lists US 2027 for both Ibrance and Xtandi [17].
Which Legal Rules Set the LOE Date?
What exclusivity periods does FDA grant?
FDA lists new chemical entity exclusivity at 5 years, new clinical investigation exclusivity at 3 years and orphan drug exclusivity at 7 years. Pediatric exclusivity adds 6 months to existing protection. The patent-challenge exclusivity for a first generic filer is 180 days [19].
How does a Paragraph IV challenge delay generic approval?
When a patent owner sues within 45 days of notice, approval can be delayed until a 30-month period ends [20]. For an application filed in the fourth year after brand approval, the stay can run until 7.5 years after that approval [20]. Brand owners and challengers use these dates to set settlement terms.
How much can patent term extension add?
Patent term extension (PTE) cannot exceed 5 years. It counts only half of the testing phase plus the full approval phase. Total remaining term after approval cannot exceed 14 years [21].
What is the biologic pathway, and what is the patent dance?
A biosimilar applicant may file 4 years after the reference product is licensed. FDA cannot approve it until 12 years after licensure [13]. Subsection (l) of the same statute sets out the “patent dance,” a structured exchange of patent lists between the applicant and the reference product sponsor [13].
Where do analysts find these dates?
The FDA Orange Book lists patent and exclusivity data for small molecules. FDA states that the Orange Book is the official vehicle for exclusivity information and that expired items are removed [19]. DrugPatentWatch organizes patent expiration dates, exclusivity, international patents, generic launch and litigation into one profile per drug [22]. Use a profile of that kind to draft the LOE calendar. Then check each date against the Orange Book and the company’s SEC filing, as Table 1 does.
Case Studies: What Happened After LOE?
Table 2 lines up five events. Each row shows the reference level before the event and the latest reported level.
Table 2. Realized erosion after LOE events
Drug
Company
LOE event
Reference level
Latest level
Change
Source
Humira
AbbVie
First US biosimilar launch, Jan 31, 2023
2022: $21.2B
2025: $4.540B
-78.6% (analysis)
[23] [6] [7]
Stelara
J&J
First US biosimilar launch, Jan 1, 2025
2023 peak: $10.9B
2025: about $6.1B (analysis)
About -44% (analysis)
[24] [14] [16] [12]
Entresto
Novartis
US exclusivity lost, July 2025
Q4 2024: about $2.198B (analysis)
Q4 2025: $1.253B
-43% (reported)
[25] [8]
Revlimid
BMS
Volume-limited US generic licenses ended Jan 31, 2026
2024: about $5.79B (analysis)
2025: $2.951B
-49% (reported)
[5] [4]
Januvia / Janumet
Merck
Settlement exclusivity ended May 2026
Q2 2025: about $622M (analysis)
Q2 2026: $429M
-31% (reported)
[1] [10]
Humira biosimilar impact: how fast did sales fall?
Humira earned $21.2 billion in 2022 [6]. Amgen launched Amjevita on January 31, 2023 [23]. AbbVie reported $8.993 billion for 2024, down 37.6%, and $4.540 billion for 2025, down 49.5% [26] [7].
What was the 2023 step?
AbbVie’s 2024 release does not state 2023 Humira revenue. Back-calculation from the 37.6% decline gives about $14.4 billion for 2023 (analysis), a drop of about 32% from 2022 [26].
How did AbbVie replace the revenue?
Skyrizi earned $17.562 billion and Rinvoq $8.304 billion in 2025 [7]. Together they are 5.7 times 2025 Humira revenue (analysis). Total net revenue rose from $56.334 billion to $61.160 billion [7].
Stelara biosimilar launch: what did J&J lose?
Stelara peaked at $10.9 billion in 2023. Sales fell 40% in the first nine months of 2025 [24]. The J&J 10-K states that Stelara was about 6.5% of 2025 revenue [14]. On $94.193 billion of total sales [16], that is about $6.1 billion (analysis).
How many ustekinumab biosimilars exist?
FDA lists eight: Wezlana (October 2023), Selarsdi (April 2024), Pyzchiva (June 2024), Otulfi (September 2024), Imuldosa (October 2024), Yesintek (November 2024), Steqeyma (December 2024) and Starjemza (May 2025) [11]. Amgen settled with J&J in 2023, and the settlement moved the launch of Wezlana to no later than January 1, 2025 [12].
Did J&J total sales still grow?
J&J total sales rose 6.0% to $94.193 billion in 2025. Stelara cost the Innovative Medicine segment about 1,040 basis points of growth [16]. CFO Joseph Wolk said the company “probably had to cut some investment” to prepare for biosimilars [24].
Entresto generic entry: what did the fourth quarter show?
On January 10, 2025, the Federal Circuit reversed a ruling that the claims of US 8,101,659 lacked written description support. It affirmed the findings on enablement and obviousness [27]. Novartis states that it lost US market exclusivity for Entresto in July 2025 [25].
Why does the full-year figure mislead?
Full-year 2025 Entresto sales were $7.748 billion, down 1%. Fourth-quarter sales were $1.253 billion, down 43% [8]. Excluding revenue deduction adjustments, the fourth-quarter decline was 32% [8]. A model that uses annual data would miss the speed of the drop.
What happens in Europe?
Novartis states that regulatory data protection for Entresto in Europe expires in November 2026 [25]. Entresto was 14.2% of Novartis net sales of $54.532 billion in 2025 (analysis from $7,748 million) [8].
Revlimid and Pomalyst: how do settlements shape the slope?
BMS states that US Revlimid generics sold under volume-limited licenses until January 31, 2026 [5]. Revlimid revenue fell 49% in 2025, and Pomalyst revenue fell 23% worldwide [4]. Together the two products were 11.8% of BMS 2025 revenue (analysis). BMS expected US Pomalyst generic entry in the first quarter of 2026 [5].
Januvia and Janumet: what does a settlement-gated cliff look like?
Januvia and Janumet earned $2.544 billion in 2025, up 12% [15]. Merck states that the Medicare negotiated price for Januvia took effect January 1, 2026 [1]. In the second quarter of 2026, sales were $429 million, down 31% on lower US demand, lower net pricing and generic competition abroad [10].
A Taxonomy of LOE Erosion: Five Archetypes
The five archetypes below are an original classification for this model. They are not an established industry standard. Each one links to a documented event.
Archetype 1: Hard drop
A small-molecule brand faces several generics at once. The Entresto fourth quarter (-43%) and the Januvia second quarter (-31%) are the data points in Table 2.
Archetype 2: Settlement-gated slope
Settlements set the entry date, and sometimes the volume. Revlimid fell 49% in 2025 while licenses were volume-limited [4] [5]. Wezlana’s launch date came from a settlement [12].
Archetype 3: Biosimilar grind
Biologics lose revenue over several years. Humira lost about 32%, 37.6% and 49.5% in three consecutive years (analysis for 2023; reported for 2024 and 2025) [26] [7].
Archetype 4: Policy cut
A government-set price lowers revenue before or after generic entry. Eliquis has a 2026 negotiated price of $231 against a $521 list price, a 56% discount [9].
Archetype 5: Shielded switch
A new formulation moves patients to a product with longer protection. Merck lists US 2043 for Keytruda Qlex [1]. The shield is only as strong as the patents that protect it. The Keytruda Qlex section below covers the dispute.
The Framework: Six Steps to Model a Multi-Year Patent Cliff
Step 1: Build the LOE calendar
List each product with its earliest credible entry date. Label each date as one of four types: confirmed by settlement or court, scheduled by expiry, contested by pending litigation, or estimated. Table 1 uses this approach.
Step 2: Measure exposure
Calculate the Exposure Ratio.
Formula: Exposure Ratio (ER)
ER = revenue of products with LOE inside the window divided by total company revenue. Merck’s Keytruda ER is 48.7%. The BMS ER for Eliquis plus Opdivo is 50.8% (analysis for both).
Step 3: Assign an erosion archetype
Pick one archetype per product from the taxonomy above. Then pick a yearly decline series. Use documented analogs, as in Table 2, and state each series as an assumption.
Formula: Retention curve
R(t) is the product of (1 minus the decline) for each year to t. For Humira-style declines of 32%, 37.6% and 49.5%, R(3) is 21.4% (analysis).
Step 4: Overlay price-setting rules
Check whether CMS has selected the product, and when the negotiated price starts. The Inflation Reduction Act section below gives the timing rules and the price data.
Step 5: Subtract mitigation
Mitigation has three parts: a shielded reformulation, new product launches and acquisitions. Measure each in revenue, not in pipeline count.
Formula: Shield-adjusted retention
Adjusted R(t) = (1 minus s) times R(t) plus s, where s is the share of revenue moved to a protected product. Keytruda Qlex was 3.6% of Keytruda revenue in the first half of 2026 (analysis) [10].
Formula: Successor ratio
Successor ratio = revenue of successor products divided by revenue of the eroding product at its pre-LOE high point. For Humira, that point is 2022. AbbVie’s ratio is 1.22 (analysis). For Merck in the first half of 2026, Winrevair ($1.114 billion) and Capvaxive ($325 million) equal 8.8% of Keytruda revenue (analysis) [10].
Step 6: Track the gap and set triggers
Subtract modeled revenue from a no-LOE baseline each year. Review the gap whenever a trigger date passes. The dashboard section below lists the triggers.
Scenario Analysis: Three Erosion Curves and a Keytruda Stress Test
What are the scenario assumptions?
All scenarios start from a flat base. Year 1 is the first full year after entry. Three decline series apply.
Curve definitions
Humira-analog: declines of 32.0%, 37.6% and 49.5% (derived from AbbVie data). Moderate: 15%, 30% and 40% (assumption). Slow: 10%, 20% and 25% (assumption). The Moderate and Slow series have no source. They bracket the Humira-analog case.
What does a $10 billion franchise lose over three years?
Table 3 applies each curve to $10 billion of exposed annual revenue, with three shield levels (analysis).
Table 3. Revenue retained and cumulative loss per $10B of exposed revenue (analysis; assumptions as stated)
Curve
Shield s
Year 1 ($B)
Year 2 ($B)
Year 3 ($B)
Year 3 retention
3-year cumulative loss ($B)
Humira-analog
0%
6.80
4.24
2.14
21.4%
16.81
Humira-analog
25%
7.60
5.68
4.11
41.1%
12.61
Humira-analog
50%
8.40
7.12
6.07
60.7%
8.41
Moderate
0%
8.50
5.95
3.57
35.7%
11.98
Moderate
25%
8.88
6.96
5.18
51.8%
8.98
Moderate
50%
9.25
7.97
6.79
67.8%
5.99
Slow
0%
9.00
7.20
5.40
54.0%
8.40
Slow
25%
9.25
7.90
6.55
65.5%
6.30
Slow
50%
9.50
8.60
7.70
77.0%
4.20
Keytruda 2029-2031: what is the upper-bound stress test?
Table 4 applies the same curves to the full 2025 Keytruda revenue of $31.68 billion. This is an upper bound. It treats all revenue as exposed from year 1, and it ignores the later EU date of 2031 [1]. It also ignores growth. Keytruda grew 7% in 2025 [15], so a flat base understates the starting point.
Table 4. Keytruda whole-franchise stress test, no shield (analysis; base $31.68B from the Merck 2025 earnings release)
Curve
Year 1 ($B)
Year 2 ($B)
Year 3 ($B)
3-year cumulative loss vs. flat base ($B)
Humira-analog
21.54
13.44
6.79
53.3
Moderate
26.93
18.85
11.31
38.0
Slow
28.51
22.81
17.11
26.6
What would the shield need to reach?
Qlex was 3.6% of Keytruda revenue in the first half of 2026 (analysis) [10]. The 25% and 50% shield cases in Table 3 need about 7 times and 14 times that share (analysis). Qlex sales rose from $35 million in the fourth quarter of 2025 to $463 million in the second quarter of 2026 [15] [10]. That is a 13-fold rise in two quarters (analysis).
How Does the Inflation Reduction Act Change the Patent Cliff?
When is a drug eligible for Medicare price negotiation?
Small-molecule drugs become eligible 7 years after FDA approval. Biologics become eligible 11 years after licensure. The negotiated price applies 9 and 13 years after approval [28]. KFF also describes a proposal to add 4 years. That proposal is not current law [28].
What did the first 17 negotiated prices look like?
Table 5 lists the ten prices that took effect January 1, 2026 and seven of the fifteen that take effect January 1, 2027.
List prices for the 2026 group are 2023 figures. List prices for the 2027 group are 2024 figures [9] [29]. The unweighted mean discount for the ten 2026 drugs is 63.1% (analysis). CMS estimated that the 2026 prices would have cut 2023 net Medicare spending by about $6 billion, or 22% [9]. It estimated that the 2027 prices would have cut 2024 net spending by about $12 billion, or 44% [29].
What happens in 2028 and 2029?
CMS announced 15 drugs for 2028 on January 27, 2026. The list includes Trulicity, Biktarvy, Orencia, Cosentyx, Erleada, Kisqali, Entyvio, Verzenio, Botox, Lenvima, Xolair, Rexulti, Xeljanz, Anoro Ellipta and Cimzia. It is the first cycle that includes Part B drugs [30].
How does the orphan drug rule change timing?
H.R. 1 widened the orphan exclusion to drugs with more than one orphan designation or approval. Milliman reports that Darzalex is ineligible under current approvals and that Opdivo and Keytruda are delayed to later years [30]. Merck still expects Keytruda selection in 2027 [1].
What happens when a biosimilar or generic is marketed?
A drug is exempt from selection once a generic or biosimilar is approved and marketed. Milliman names Humira, Prolia and Eylea as examples [30]. J&J states that CMS will remove Xarelto and Stelara from the Selected Drug List beginning in 2027 [14].
When do price cuts and generic entry stack?
Four brands show different orders of events (analysis from cited dates). Stelara had a biosimilar in January 2025 and a negotiated price in January 2026, 12 months later [12] [9]. Entresto lost US exclusivity in July 2025 and had a negotiated price in January 2026, 6 months later [25] [9]. Januvia had a negotiated price in January 2026 and settlement exclusivity ended in May 2026, 4 months later [9] [1]. Eliquis has a negotiated price in 2026 and settled generic entry in 2028 [9] [5].
Does a price cut mean falling revenue?
Not by itself. Eliquis revenue rose 8% worldwide in 2025 to $14.443 billion [4]. BMS guides to Eliquis growth of 10% to 15% in 2026 [4]. BMS also states that it will provide Eliquis free to Medicaid from January 1, 2026 [5].
Who Is Exposed? Exposure Ratios for Five Companies
Table 6 combines company filings into one comparison. All ratios are analysis.
Table 6. Revenue concentration in products at or near LOE (fiscal 2025)
Company
Exposed product(s)
2025 product revenue
2025 company revenue
Share
Status
Source
Merck
Keytruda
$31.68B
$65.01B
48.7%
US expiry 2028
[1] [15]
BMS
Eliquis + Opdivo
$24.49B
$48.19B
50.8%
US 2028
[4] [5]
BMS
Revlimid + Pomalyst
$5.68B
$48.19B
11.8%
Eroding
[4]
J&J
Darzalex
About $14.1B
$94.19B
15.0%
US 2029
[14] [16]
J&J
Stelara
About $6.1B
$94.19B
6.5%
Eroding
[14] [16]
Novartis
Entresto
$7.75B
$54.53B
14.2%
Eroding
[8]
AbbVie
Humira
$4.54B
$61.16B
7.4%
Eroded
[7]
Which company carries the highest concentration?
In this table, BMS shows 50.8% in two products and Merck shows 48.7% in one. The two companies differ in structure. Merck’s exposure rests on one molecule. BMS’s exposure splits across an anticoagulant and a PD-1 antibody, with different patent and settlement paths [5].
What is Pfizer’s exposure?
Pfizer states that it expects “a significant reduction of revenue from patent-based or regulatory exclusivity expiries in 2026 through 2030” [17]. Its table lists US 2026 for Xeljanz, Prevnar 13 and Vyndaqel. It lists US 2027 for Eliquis, Ibrance and Xtandi [17].
Keytruda Qlex vs. Keytruda: Does Subcutaneous Dosing Extend Protection?
What is Keytruda Qlex?
Keytruda Qlex combines pembrolizumab and berahyaluronidase alfa for subcutaneous use [1]. BioSpace reported on September 22, 2025 that the FDA approved it, with dosing every three or six weeks. In a lung cancer study, the overall response rate was 45% for Qlex and 42% for intravenous Keytruda. Merck said it would price Qlex at parity with the intravenous form [31].
How strong is the patent shield?
Merck lists US 2043 and EU 2031 for Qlex [1]. Halozyme disputes the product. Halozyme sued MSD in the US over 15 patents. MSD has invalidated claims of 4 of them before the Patent Trial and Appeal Board, and 13 more petitions were pending at the time of the report [32].
What have European courts decided?
In December 2025, the Munich Regional Court granted Halozyme a preliminary injunction against distribution of Keytruda SC in Germany [32]. On July 14, 2026, the District Court of The Hague dismissed Halozyme’s request to bar sales in Denmark and Sweden. The European patent at issue expires on December 27, 2032. The merits hearing in The Hague was set for July 31, 2026 [32].
What does this mean for the model?
Treat the shield variable s as contested, not confirmed. Label Qlex protection “contested” in the LOE calendar until the US and EU cases resolve.
Biosimilar Launch Rules: What Is Changing at FDA?
What did FDA propose in October 2025?
FDA’s draft guidance would let most biosimilar makers use comparative analytical assessments in place of comparative efficacy studies. A study could still be required in some cases, such as locally acting products [33]. FDA also plans final guidance stating that switching studies are not required to show interchangeability [33].
FDA Commissioner Marty Makary said: “We are taking a strong stand to advance and promote interchangeability” [33].
How much do generics and biosimilars save?
The Association for Accessible Medicines (AAM) reports that generics were about 90% of US prescriptions and about 12% of spending in 2024. It reports $467 billion in generic savings in 2024 and $20.2 billion in biosimilar savings, or $56.2 billion since 2015 [34]. FDA reports 773 generic applications fully approved in 2023, with estimated net savings of $18.6 billion over 12 months [35].
Is there a biosimilar gap?
AAM states that 90% of brand biologics losing protection in the next ten years have no biosimilar in development [34]. AAM is an industry association, so treat this as an advocacy figure. For the model, it means that biologic erosion can be slower than the Humira-analog curve when no developer is in the field.
What This Means for Brand Manufacturers, Challengers, Payers and Medical Teams
What this means for brand manufacturers
Track conversion to a protected formulation as a leading indicator. The Qlex series shows how fast it can move (13-fold in two quarters) and how small the base still is (3.6% of Keytruda revenue). Design settlements with the slope in mind. Revlimid shows what volume-limited licenses do to a curve [5] [4].
What this means for generic and biosimilar developers
Rank targets by exposure, entry date and competitor count. Eight ustekinumab biosimilars were approved within 20 months [11]. Eligible products with no developer, per AAM, may offer less crowded entry [34].
What this means for payers and Part D plans
Model the price cut and the generic entry as two separate events. The 12-month, 6-month and 4-month gaps in this article show that the order varies by drug.
What this means for medical affairs and pharmacovigilance teams
When an LOE date passes, patients can move among the brand and several copies. FDA plans to remove switching studies as an interchangeability requirement [33]. Teams that support a brand should plan for safety reporting that names product and manufacturer. This is our recommendation. No cited source requires it.
What this means for investors and business development
Merck’s second-quarter 2026 release shows two acquisitions. It completed Terns for $6.8 billion, with a $5.7 billion R&D charge. It also recorded a $9.0 billion one-time R&D charge for Cidara [10]. Q1 2026 biotech M&A reached $84 billion against $44.4 billion a year earlier, per Dealogic data in a Reuters report [3]. Patrice Mesnier of Oldenburg Capital Partners said of buyers: “They are no longer buying optionality. They are buying time.” [3]
Early-Warning Dashboard: Dated Triggers to Monitor
Table 7 lists dated events from the sources in this article. Add litigation dockets and Orange Book changes as they occur.
Table 7. Dated LOE and price-setting events
Date
Event
Date type
Source
Nov 2026
EU Eliquis composition-of-matter patents and SPCs expire
Scheduled
[5]
Nov 2026
EU regulatory data protection for Entresto expires
Scheduled
[25]
Jan 1, 2027
Negotiated prices start for Ozempic family, Ibrance, Xtandi, Pomalyst, Trelegy, Calquence and Janumet
Confirmed
[29]
2027
US basic patent expiry for Ibrance, Xtandi and Lynparza
Scheduled
[17] [1]
2027
Merck expects Keytruda selection for price setting
Company expectation
[1]
2028
US expiry for Keytruda, Opdivo and settled Eliquis generic entry
Scheduled / settled
[1] [5]
Jan 1, 2029
Government-set Keytruda price, if selected in 2027
Company expectation
[1]
2029
US Darzalex patent families expire
Scheduled
[14]
Jul 2030
Generic Lenvima entry under settlements
Settled; litigation ongoing
[1]
Which leading indicators matter most?
Four indicators carry the most signal. First, quarterly revenue in the last two quarters before LOE, as Entresto’s fourth quarter shows. Second, conversion share to a protected formulation. Third, PTAB and court rulings on the protecting patents. Fourth, each CMS selection list.
Key Takeaways
Evaluate puts 2025-2030 revenue losing exclusivity above $300 billion. Its method is not stated [2].
Keytruda is 48.7% of Merck sales, and US expiry is 2028 [1].
Eliquis and Opdivo are 50.8% of BMS revenue, and both have US 2028 dates [4] [5].
Humira lost 78.6% of revenue in three years, yet AbbVie grew because successors earned 1.22 times Humira’s 2022 revenue (analysis) [7].
Quarterly data show LOE damage earlier than annual data. Entresto fell 1% for the year and 43% in the last quarter [8].
Negotiated prices for the first ten drugs average 63.1% below list (analysis) [9].
Keytruda Qlex is 3.6% of Keytruda revenue, and its patents are in dispute [10] [32].
A $10 billion franchise can lose $4.2 billion to $16.8 billion over three years, depending on curve and shield (analysis, Table 3).
FAQ
How long does the 30-month stay last, and when does it start?
The stay is 30 months from the date the patent owner receives notice of the challenge. It applies only if the owner sues within 45 days of that notice [20].
How many years can patent term extension add?
Up to 5 years. The remaining term after approval plus the extension cannot exceed 14 years [21].
When can a biosimilar company file, and when can FDA approve?
A company can file 4 years after the reference product is licensed. FDA can approve 12 years after licensure [13].
What does the FDA Orange Book list?
It lists patents and exclusivities for approved drugs. A pediatric-exclusivity patent appears twice, once with the original date and once with the six-month extension. Expired items are removed [19].
How many generic drugs did FDA approve in 2023, and what did they save?
FDA fully approved 773 generic applications in 2023. It estimated $18.6 billion in net savings over the 12 months after approval [35].
What share of US prescriptions do generics fill?
AAM reports about 90% of 2024 prescriptions and about 12% of spending [34].
Merck reported a $5.7 billion charge for Terns, which closed for $6.8 billion in the second quarter, and a $9.0 billion one-time charge for Cidara [10].
How many patents does Halozyme assert against Keytruda Qlex in the US?
Fifteen. MSD has invalidated claims of 4 at the PTAB, and 13 more petitions were pending in the July 2026 report [32].
When do the European Eliquis patents expire?
BMS states that the apixaban composition-of-matter patents and related SPCs expire in November 2026. Generics already sell in some EU countries [5].
