Keytruda loss of exclusivity: two licences, two sets of dates

Merck lists the US compound patent for intravenous Keytruda at 2028 and for subcutaneous Keytruda Qlex at 2043. Qlex is a separate FDA licence. This page records what the public record showed when each source was read, between 15 and 23 October 2026, and where it shows nothing.

Who and what does this page refer to?

• Keytruda is the brand name for pembrolizumab, which a Zydus Lifesciences and Formycon release (13 October 2026) describes as an immune checkpoint inhibitor that binds to and blocks the PD-1 receptor. PD-1 (programmed cell death protein 1) is a receptor on immune cells. Keytruda Qlex is pembrolizumab combined with berahyaluronidase alfa-pmph. Keytruda is licensed for intravenous (IV) use, into a vein, and Keytruda Qlex for subcutaneous (SC) use, under the skin. In Europe Merck markets the subcutaneous product as Keytruda SC.
• Merck is Merck & Co., Inc., Rahway, N.J., USA, which describes itself as known as MSD outside the United States and Canada (Merck release, 4 August 2026). Merck's 10-K describes Merck Sharp & Dohme LLC as its subsidiary. The complaint in the US case described below names Merck Sharp & Dohme Corp. as defendant. The FDA Purple Book names Merck Sharp & Dohme LLC as applicant for Keytruda Qlex and MSD International Business GmbH as applicant for Keytruda. MSD BV is described by Halozyme as Merck's central European marketing authorisation holder and worldwide packaging and distribution hub.
• Halozyme is the short form this page uses for the party that alleges Merck's subcutaneous product infringes its patents. Where a statement comes from Halozyme's own press release, the page uses the issuer's name as the release gives it, Halozyme Therapeutics, Inc.; where it comes from the US court record, the page uses the plaintiff's name as the court does, Halozyme, Inc. MDASE is the name for Halozyme's portfolio of patents on modified hyaluronidase, an enzyme; Merck's 10-Q says Halozyme alleges certain MDASE patents cover an ingredient in Merck's subcutaneous product.
• BLA is a Biologics License Application, the application to the FDA for licensure of a biological product. Section 351(k) of the Public Health Service Act (42 U.S.C. 262(k)) is the FDA pathway for biosimilar applications. A biosimilar is a biological product shown to be highly similar to an already-licensed reference product.
• Purple Book is the FDA's database of licensed biological products. openFDA is the FDA's public data service; this page uses its Drugs@FDA endpoint, which returns FDA application records.
• Post-grant review (PGR) and inter partes review (IPR) are proceedings before the US Patent Trial and Appeal Board (PTAB) in which a party asks that a patent's claims be held invalid or unpatentable. A preliminary injunction is a court order, made before a case is finally decided, that requires a party to refrain from an activity while the case continues.
• NSE is the National Stock Exchange of India, where Zydus Lifesciences filed its release. BsUFA is the Biosimilar User Fee Amendments, which the release cites for the FDA's review timeline.
• Loss of exclusivity (LOE) is the point at which legal barriers, such as patents and regulatory exclusivity, no longer prevent competing versions from entering. A patent expiry date is one input to it, not the same thing. LOE Edge is the loss-of-exclusivity intelligence product from Phontix AI Private Limited.

Large companies operate through several legal entities, often one for each country or function. Press releases, court filings and regulatory records each name the entity that acted in that document, and these are not always the same one. This page uses the name each source gives. It does not treat two named entities as one company, or say that one controls the other, unless a source says so.

When does Keytruda lose exclusivity?

There is no single date in the public record. Merck's annual report lists the US compound patent for intravenous Keytruda at 2028 and for Keytruda Qlex at 2043. Qlex is a separate FDA licence (BLA 761467). The FDA registers, read on 15 October 2026, showed no licensed Keytruda biosimilar.

• Merck-listed US patent years: Keytruda 2028, Keytruda Qlex 2043. Source: Merck & Co., Inc., Form 10-K for the year ended 31 December 2025, Item 1, patent table. These are Merck's disclosures; Phontix AI has not independently checked patent term at the USPTO.
• Two FDA licences, not one. Keytruda is BLA 125514 (original approval 4 September 2014). Keytruda Qlex is BLA 761467 (original approval 19 September 2025). Source: Drugs@FDA data via openFDA and the FDA Purple Book, read 15 October 2026.
• No licensed biosimilar on the FDA registers. openFDA lists two pembrolizumab applications, both Merck's, and the Purple Book shows no biosimilar for either product (Purple Book database last updated 30 September 2026). These registers list licensed products, so this says nothing about any application under review.
• First publicly announced FDA acceptance of a Keytruda biosimilar application: 13 October 2026, according to the companies. Zydus Lifesciences and Formycon AG jointly announced that the FDA accepted the BLA for FYB206; the companies say that, to the best of their knowledge, this is the first publicly announced acceptance of a filing for a proposed Keytruda biosimilar. Zydus holds exclusive commercialisation rights for the United States and Canada. Source: joint Zydus Lifesciences and Formycon press release, filed by Zydus with the NSE, 13 October 2026.
• Q2 2026 sales as reported: Keytruda and Keytruda Qlex combined $8,366 million, up 5% (4% excluding currency); Keytruda Qlex alone $463 million. Source: Merck second-quarter 2026 results, Form 8-K Exhibit 99.1, 4 August 2026.

Plain-language summary. A patent year is not the date a competitor can sell. Keytruda is two FDA-licensed products with different Merck-listed patent years, and the subcutaneous one is the subject of patent litigation in the US and Europe brought by Halozyme. The public record reviewed for this page does not give an entry date for either product.

Method note. Every figure below names its source and date. Evidence is primary (SEC, FDA, statute, company releases) except where marked secondary. Phontix AI calculations are labelled as such. Gaps are stated in the text and are not estimated. How Phontix AI reads FDA registers is described on the LOE Edge methodology page.

What dates does Merck give for Keytruda and Keytruda Qlex?

Merck's 10-K for the year ended 31 December 2025 lists patent expiry years by product and market. Patent expiry is not loss of exclusivity: regulatory exclusivity, patent term adjustment and litigation each move the date a competitor can enter.

Source: Merck & Co., Inc., Form 10-K, year ended 31 December 2025, Item 1, "Patents, Trademarks and Licenses", read in full on SEC EDGAR on 15 October 2026. Merck's table key defines N/A as "Currently no marketing approval." These are Merck's disclosures, not independently checked at the USPTO or EPO.

Two footnotes qualify the table. Merck states that the Keytruda compound patent family contains two additional patents that expire in 2029 due to patent term adjustment, and that it expects them to be the subject of litigation in the future. For Qlex in the EU, Merck states that a patent application is pending which, if granted, will expire in 2040. Both are Merck statements, not Phontix AI forecasts.

Is Keytruda Qlex a separate licence from Keytruda?

Yes, on the FDA's records. Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph) is BLA 761467, an original application classified by the FDA as Type 1 (new molecular entity), with original approval on 19 September 2025. Keytruda is BLA 125514, with original approval on 4 September 2014. Both are section 351(a) licences, and the Purple Book lists each as a reference product. Sources: Drugs@FDA data via openFDA; FDA Purple Book product pages for BLA 125514 and BLA 761467, read 15 October 2026.

Route of administration. Under section 351(k), an application must include information showing that the biosimilar's route of administration, dosage form and strength are the same as those of the reference product (42 U.S.C. 262(k)(2)(A)(i)(IV)). The statute defines a reference product as the single licensed biological product against which a biosimilar is evaluated (42 U.S.C. 262(i)(4)). Our reading, at medium confidence: Keytruda is licensed for intravenous use and Keytruda Qlex for subcutaneous use, so a biosimilar application referencing Keytruda would be for an intravenous product. The statutory text is clear on the same-route requirement; applying it to these two products is our inference.

Exclusivity periods. The statute bars FDA approval of a biosimilar until 12 years after the date on which the reference product was first licensed, and bars submission of the application until 4 years after that date (42 U.S.C. 262(k)(7)(A) and (B)). The Purple Book field "Date of First Licensure" is blank for both BLA 125514 and BLA 761467 (read 15 October 2026), so neither period can be computed from the public record. Section 262(k)(7)(C) also states that those two periods do not apply to a licence for a supplement, or to a subsequent application by the same sponsor for a change, not including a modification to the structure of the biological product, that results in a new route of administration, dosage form or delivery system, among other things. Whether the FDA treats BLA 761467 as falling within that provision is not stated in the records reviewed. Our reading, at low confidence: the statutory text gives no basis for assuming that Keytruda Qlex carries its own twelve-year period. This page states no exclusivity end date for either product. Sources: 42 U.S.C. 262, read on Cornell Legal Information Institute and in the 2023 edition on govinfo.gov, 15 October 2026.

Which Keytruda biosimilars have been publicly announced?

This list is built from announcements. The FDA does not disclose that a biological product application exists before approval unless it has been publicly disclosed or acknowledged (21 CFR 601.51(b)). So any count of pending applications can only come from announcements, and none of the lists below is a closed set.

Inclusion rule: events found in the sources reviewed for this page; the biosimilar searches were run on 15 October 2026. Where a row rests on secondary reporting alone, it is labelled. A wider list of developers from a single secondary source was not added. The table is not exhaustive.

On FYB206, the companies state that the BLA was submitted in the third quarter of 2026, that the product was developed without a comparative Phase III efficacy trial following a development pathway agreed with the FDA in early 2025, and that under BsUFA the FDA aims to complete its review within twelve months of submission. They state that FYB206 is an investigational product that has not received regulatory approval in any country, and that biosimilarity has not been established by regulatory authorities and is not claimed. An FDA action date and a launch date are different events; this page predicts neither.

Merck's 10-Q for the quarter ended 30 June 2026 states that a biosimilar of Keytruda launched in Argentina in 2025. Outside the US, Pearce IP (10 August 2026, secondary) reports pembrolizumab biosimilar approvals or launches by Bioeticos in Paraguay, Biocad in Vietnam and Sana Pharma in Jordan. Phontix AI has not checked those regulatory records.

What has been litigated over subcutaneous Keytruda?

Halozyme alleges that patents in its MDASE portfolio cover an ingredient in Merck's subcutaneous pembrolizumab product. Merck contests the allegations. The record below is past tense and attributes each position to the party asserting it. "As at" dates are the dates of the source. JUVE Patent (9 October 2026) uses "Halozyme" and "MSD" for the parties in the Dutch proceedings. This page does not state which legal entities of either group are the named parties in the German and Dutch proceedings.

• United States. In the US District Court for the District of New Jersey, case number 2:25-cv-03179, Halozyme, Inc. is the plaintiff and Merck Sharp & Dohme Corp. is the defendant named in the complaint, which was filed on 24 April 2025 (CourtListener copy of the court docket, read 22 October 2026). Halozyme alleges that Merck's activities relating to subcutaneous pembrolizumab infringe or will infringe 15 MDASE patents (Merck Form 10-Q signed 7 August 2026; Halozyme release, 7 October 2026). The plaintiff's complaint (ECF No. 1, read in part on 22 October 2026) carries the same case number, asserts 15 patents from a single family that the complaint says embody the plaintiff's MDASE technology, and refers to subcutaneous administration of Keytruda. The docket records that on 6 August 2026 the court administratively stayed the case pending the outcome of the patent reviews before the PTAB and, if applicable, the US Court of Appeals for the Federal Circuit, with a status conference set for 23 November 2026. The CourtListener copy's last known filing is dated 12 August 2026, and it states that its entries may not be up to date. As at 7 August 2026, Merck states that all 15 patents are the subject of its PGR petitions or of separately filed IPR petitions; that the PTAB instituted 14 PGR petitions; that the PTAB has issued final written decisions on four of them finding every challenged claim unpatentable; that Director Review requests filed by Halozyme to date have been denied; and that institution decisions on the IPR petitions were pending. Halozyme's position on those proceedings is not stated in the sources reviewed.
• Germany. A preliminary injunction was awarded against Merck on European Patent EP 2 797 622 (EP622), prohibiting sales of Keytruda SC in Germany, following a hearing in December 2025 (Merck Form 10-Q signed 7 August 2026). Halozyme dates the injunction at 4 December 2025 (Halozyme release, 7 October 2026). As at 7 August 2026, Merck states that it has appealed and that the appeal hearing was set for 19 November 2026. The sources reviewed report no later change; the appeal outcome is not on the record reviewed.
• Netherlands, 22 July 2026. The District Court of The Hague rejected a Halozyme application for a preliminary injunction covering Denmark and Sweden while accelerated main proceedings were pending. JUVE Patent (22 July 2026) reports that the court held a statement in Merck's written pleading was not a binding undertaking; the report describes no finding on the patent's validity or infringement.
• Netherlands, 7 October 2026. Halozyme announced that the specialised Dutch patent court of The Hague found Merck to be infringing EP622, rejected Merck's arguments that the patent is invalid, and ordered MSD BV to refrain from manufacturing, offering, placing on the market, using, importing or stocking Keytruda SC for those purposes in Belgium, Denmark, France, Ireland, Italy, Sweden, Switzerland and the Netherlands (Halozyme release, 7 October 2026). Halozyme states that intravenous Keytruda is not covered by the patent or the order. JUVE Patent (9 October 2026) reports that the District Court of The Hague ruled in main infringement and revocation proceedings: it dismissed Merck's revocation action against the Dutch part of EP622 and granted Halozyme's infringement counterclaims. JUVE reports that MSD must stop within seven days of the judgment being served, with penalties of up to €50 million, and that the cross-border part of the injunction ceases to apply in any country where the national part of the patent is revoked. The judgment itself was not read. As at 22 October 2026, the sources reviewed (Halozyme's newsroom, JUVE Patent of 9 October 2026, Fierce Pharma of 7 October 2026) report no appeal; appeal status is not confirmed.
• Merck's position. Fierce Pharma (7 October 2026) reports that Merck disagreed strongly with the decision in an emailed statement. It reports a Merck spokesperson as saying that Merck considers Halozyme's patent invalid globally and the infringement allegation without merit, and will be evaluating next steps. No Merck release or filing on the 7 October 2026 order was found in the sources reviewed.
• Other proceedings. Merck states that it filed revocation actions against EP622 in the UK, France, Germany, the Netherlands, Denmark, Sweden and Switzerland; that Halozyme counterclaimed for an injunction in the UK but undertook not to enforce any injunction there until validity is finally determined; and that in May 2026 Halozyme consented to revocation of EP622 in the UK (Merck Form 10-Q signed 7 August 2026).
• Merck's disclosure. Merck's 10-K states that the timing of commercial availability of Keytruda SC in individual EU countries depends on multiple factors, including the completion of national reimbursement procedures and the outcome of litigation with Halozyme.

Patent EP 2 797 622 was searched by number for this page. No US patent numbers are named here.

What do Merck's reported sales show?

Merck reports Keytruda and Keytruda Qlex combined, and separates Qlex in the quarterly release. Growth is shown at actual and at constant (excluding currency) rates.

Sources: Merck Form 8-K Exhibit 99.1, 4 August 2026 (Q2 and the product split); Merck Form 10-Q, quarter ended 30 June 2026 (Q2 and first half); Merck Form 10-Q, quarter ended 31 March 2026 (Q1); Merck Form 10-K, year ended 31 December 2025 (full year). The newest reported period when these sources were read on 15 October 2026 was Q2 2026.

In Q2 2026 Keytruda Qlex sales were $463 million and standalone Keytruda sales were $7,904 million, down 1% (down 2% excluding currency). Qlex sales in Q1 2026 were $128 million. The release does not attribute the standalone movement to a cause, and this page does not either. The two lines sum to $8,367 million, against the $8,366 million Merck reports for the combination; the release does not explain the $1 million difference and states elsewhere that amounts may not sum due to rounding. Phontix AI calculation: Qlex was about 5.5% of combined Q2 2026 sales ($463 million of $8,366 million).

Merck's 10-Q for the quarter ended 30 June 2026 states that the company anticipates the impact of biosimilar erosion to Keytruda sales will be immaterial in 2026. The same passage states that a biosimilar of Keytruda launched in Argentina in 2025 and that Merck expects further launches in smaller international markets during 2026.

What does Merck expect for Medicare price negotiation?

Merck's 10-K states that it expects Keytruda to be selected in 2027 for government price setting, which would become effective on 1 January 2029. Merck's 10-Q signed 7 August 2026 repeats this expectation. These are Merck's expectations, and this page does not state what any CMS list shows.

The statute contains two rules that refer to biosimilars (42 U.S.C. 1320f-1, read on Cornell Legal Information Institute on 15 October 2026):

• Selected-drug status. A selected drug remains selected for each year beginning before the first year that begins at least nine months after the Secretary determines that at least one biosimilar, licensed with the selected drug as its reference product, is marketed pursuant to that licensure (subsection (c)(1)).
• Delay of selection. For a biological product that would otherwise be selected, selection is delayed by one year if the Secretary determines there is a high likelihood that a biosimilar will be licensed and marketed before the date two years after the selected drug publication date, and a biosimilar manufacturer requests the delay before that publication date (subsection (f)).

Whether either rule could apply to Keytruda or Keytruda Qlex is not addressed in the sources reviewed. No entry date for any Keytruda biosimilar is assumed here.

What is the status of each Keytruda product?

"None listed" means none licensed: the Purple Book and Drugs@FDA list licensed products, so this says nothing about any application under review. Where the Purple Book and Drugs@FDA name different entities, both are shown.

How should a team deciding whether to build read these dates?

• Read 2028 as Merck's disclosed US patent year for intravenous Keytruda. It is not an entry date, and it does not address regulatory exclusivity or litigation.
• Read the Qlex row as a separate product. Its dates do not move the intravenous row. Our reading, at medium confidence, is that a biosimilar of one is not a biosimilar of the other, because the statute requires the same route of administration as the reference product.
• Read the biosimilar table as announcements only. The FDA does not publish applications under review. For a biologic that already has licensed US biosimilars, see Denosumab biosimilars.
• Read the Halozyme record as the parties' positions. Each court outcome applies to the named patent, market and defendant.
• Read the blank first-licensure field as a limit on what the public record shows. Vedolizumab biosimilars reports the same blank field for another biologic. Until the FDA populates it, the periods in section 262(k)(7) cannot be computed, and whether Qlex carries its own period is not settled by the text we read.

Frequently asked questions

Related reading

• Vedolizumab biosimilars: Takeda's New Jersey suits and London claims over another biologic.
• Denosumab biosimilars: US biosimilar entries and Amgen's sales.
• Apixaban loss of exclusivity: a small-molecule comparison.

What LOE Edge shows today

LOE Edge is the loss-of-exclusivity intelligence product from Phontix AI Private Limited. Its demo reads FDA records only: the Orange Book and drug label data through openFDA for small molecules, and the Purple Book data file for biologics. It has no EU5 or India data and no forecast view. For biologics it shows a dash for confidence, because patent-structure scoring does not apply to them.

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Methodology and sources

Phontix AI Private Limited first compiled this page on 15 October 2026 and last changed it on 25 October 2026, from the sources below. Each dated statement gives the date its source was read. Evidence labels: P = primary (regulator, statute, filing, company release); S = secondary (trade or legal press, outlet and date named in the text). Nothing on this page is investment advice. Named companies are discussed on the basis of public records only.

1. Merck & Co., Inc., Form 10-K, year ended 31 December 2025, SEC EDGAR. P.
2. Merck & Co., Inc., Form 10-Q, quarter ended 30 June 2026, signed 7 August 2026, SEC EDGAR. P.
3. Merck & Co., Inc., Form 10-Q, quarter ended 31 March 2026, SEC EDGAR. P. Used for the Q1 2026 sales row only.
4. Merck & Co., Inc., Form 8-K Exhibit 99.1, second-quarter 2026 results, 4 August 2026, SEC EDGAR. P.
5. FDA, Drugs@FDA data via openFDA drugsfda endpoint, BLA 125514 and BLA 761467, read 15 October 2026. P.
6. FDA, Purple Book product details, BLA 125514 (Keytruda), read 15 October 2026; database last updated 30 September 2026. P.
7. FDA, Purple Book product details, BLA 761467 (Keytruda Qlex), read 15 October 2026; database last updated 30 September 2026. P.
8. 42 U.S.C. 262, Regulation of biological products, 2023 edition on govinfo.gov; also read on the Cornell Legal Information Institute site. Both read 15 October 2026. P (statute text).
9. 42 U.S.C. 1320f-1, Selection of negotiation-eligible drugs as selected drugs (Cornell Legal Information Institute), read 15 October 2026. P (statute text; the official uscode.house.gov page could not be opened).
10. Zydus Lifesciences and Formycon AG, joint press release filed with the NSE, 13 October 2026. P (company).
11. Halozyme Therapeutics, Inc., press release, 7 October 2026. P (company; allegations and positions are Halozyme's).
12. JUVE Patent, The Hague dismisses Halozyme's PI bid against MSD over Keytruda, 22 July 2026. S.
13. Fierce Pharma, Halozyme wins Keytruda SC injunction in several European markets, 7 October 2026, reporting an emailed Merck statement and remarks from a Merck spokesperson. S.
14. OncLive, Pembrolizumab biosimilar meets primary Phase 1 and Phase 3 end points in NSCLC, 29 June 2026. S.
15. Pearce IP, Samsung Bioepis files first Korean application for biosimilar to Keytruda, 10 August 2026. S. The article's own account of Paraguay, Vietnam and Jordan is also secondary.
16. Cipla and Qilu, exclusive US licensing and supply agreement release, 3 September 2026, PR Newswire via BioSpace. P (company, republished).
17. 21 CFR 601.51(b), disclosure of biological product files. eCFR.
18. Free Law Project, CourtListener RECAP copy of the docket, case 2:25-cv-03179 (D.N.J.), read 22 October 2026. S (a copy of PACER data; CourtListener states entries may not be up to date).
19. JUVE Patent, Halozyme takes the win over MSD's cancer drug Keytruda in the Netherlands, 9 October 2026. S.
20. US District Court for the District of New Jersey, case 2:25-cv-03179, complaint, ECF No. 1, filed 24 April 2025, read on 22 October 2026 on a copy hosted by Pearce IP (pages 1 and 3). Caption on page 1: plaintiff Halozyme, Inc.; defendant Merck Sharp & Dohme Corp. P (court filing), but not obtained from PACER.

Phontix AI calculations: Qlex share of Q2 2026 combined sales (463 / 8,366 = 5.5%). No other figure on this page is our own calculation or modelling.

Limits. Drugs@FDA and the Purple Book list licensed products, not applications under review. Patent years are Merck's disclosures and were not checked at the USPTO or EPO. Litigation is described from Merck's SEC filings, company releases and trade or legal press, and, for the New Jersey case, from the CourtListener copy of the docket. The complaint was read in part (pages 1 and 3) on a copy hosted by Pearce IP; no judgment was read.