Biosimilar Cases to Watch: Prolia/Xgeva and Denosumab Competitors

With 3 approved biosimilars, at least 5 more awaiting approval, and launches expected to start as early as May 31, 2025, the Prolia / Xgeva (reference denosumab) $3.8 billion market is being closely watched.¹ Five Biologics Price Competition and Innovation Act (BPCIA) litigations asserting a total of 47 patents have been filed to date, and while two have settled, the remaining early-stage cases were recently consolidated into a Multidistrict Litigation (MDL) in the District of New Jersey (DNJ).² We give an overview of the state of denosumab biosimilars and explore the history and implications of the related patent disputes.

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Sandoz’s Jubbonti/Wyost (denosumab-bbdz) were the first interchangeable biosimilar approvals in March 2024,³ followed by Samsung Bioepis’s Ospomyv/Xbryk (denosumab-dssb) interchangeable biosimilars in February 2025,⁴ and Celltrion’s Steoboclo/Osenvelt (denosumab-bmwo).^5* At least 5 abbreviated biologics license applications (aBLAs) await FDA-approval, including Fresenius Kabi’s FKS518,⁶ Teva’s TVB-009P,⁷ Organon / Henlius’s HLX14,⁸ Accord / Intas’s INTP23,⁹ and Gedeon Richter / Hikma’s RGB-14.¹⁰

Sandoz settled the first BPCIA litigation (1:23-cv-02406 (D.N.J.)) after about 1 year,¹¹ stipulating that US Patent No. 7,364,736 claiming antibodies and compositions was valid and infringed, agreeing to an injunction through its 2/19/2025 expiration and a launch date of 5/31/2025, or earlier under certain undisclosed circumstances. A 6-day preliminary injunction hearing was held in this case, but the stipulated injunction was filed the same day the court was set to rule on the injunction. Celltrion recently stipulated to the infringement and validity of the 29 patents asserted against it, approximately 8 months into its BPCIA litigation (1:24-cv-06497 [DNJ]), agreeing to a launch date as early as 6/1/2025.¹²

The remaining 3 cases against Samsung Bioepis (1:24-cv-08417 [DNJ]), Fresenius Kabi (1:25-cv-01080 [DNJ]), and Accord (1:25-cv-01305 [DNJ]) were just consolidated in MDL 1:25-md-03138 [DNJ]). In its decision,² the MDL panel noted its considerations in consolidating the cases, which may be important for future biosimilar litigants seeking centralization. Important to the panel were the common questions of fact, convenience and efficiency of centralization, the early procedural posture of the cases, the common set of asserted patents, and avoiding the risk of duplicative discovery and inconsistent rulings.

In finding DNJ the most appropriate venue, the panel noted that the judge was already presiding over 2 of the pending actions and previously oversaw the Sandoz action, where she became familiar with the technology through a technical tutorial and preliminary injunction hearing. The panel rejected defendants’ arguments that consolidation would cause confidentiality issues between the competitors, noting similar arguments were rejected in the Eylea (reference aflibercept) MDL. The panel was also not concerned that the cases included nonoverlapping patents and may include inconsistent arguments based on the different manufacturing methods for each biosimilar.

Of note, there have not been any Patent Trial and Appeal Board proceedings filed against Prolia/Xgeva patents, which is quite unusual. Remicade (reference infliximab) is the only other reference product facing biosimilar competition that did not also receive a petition for inter partes or post-grant review (IPR).¹³ It is possible this is because the majority of the patents asserted in the Prolia/Xgeva biosimilar litigations are manufacturing patents, which is the least frequently challenged type of patent in IPRs.

Also unusual in this set of litigations are the terms of the settlement agreements,^14,15 which allow for only a 1-day period of exclusivity for the first settling biosimilar. In litigations for biosimilars of other reference products, settlement agreements have typically included exclusivities of approximately 2 to 6 months for the first settling biosimilars.

An open question is whether there will be an at-risk launch given Samsung Bioepis’s recent biosimilar approval. This seems unlikely given the Court’s scheduling order requiring submission of launch plans and the lack of a preliminary injunction hearing scheduled thus far.¹⁶ It’s possible that Samsung Bioepis agreed to a consent injunction until at least May 31, 2025, but that information has thus far not been publicly disclosed. At-risk launch may not be out of the question for Samsung Bioepis, though, as it previously launched its Remicade biosimilar Renflexis (infliximab-abda) during pending litigation.¹⁷

With the pending litigations in early discovery, it remains to be seen how the denosumab market will progress. It’s possible, given the imminent launches of competitors, the other biosimilars may soon settle to secure launch dates as close to the others as possible to remain competitive in the market.

References

Prolia^® / Xgeva^® (denosumab). Biologics HQ. Updated February 28, 2025. Accessed March 9, 2025. https://biologicshq.com/product/prolia-xgeva/

Transfer order for case MDL No. 3138. United States Judicial Panel on Multidistrict Litigation. February 6, 2025. Accessed March 9, 2025. https://biologicshq.com/wp-content/uploads/2025/03/MDL-Panel-Transfer-Order-2025-02-06-EDNC-5-24-cv-00642-37.pdf

1. Jubbonti^® / Wyost^® (denosumab-bbdz). Biologics HQ. Updated February 28, 2025. Accessed March 9, 2025. https://biologicshq.com/product/jubbonti-wyost/
2. Ospomyv / Xbryk (denosumab-dssb). Biologics HQ. Updated February 28, 2025. Accessed March 9, 2025. https://biologicshq.com/product/ospomyv-xbryk/
3. Jeremias S. FDA approves third pair of denosumab biosimilars. The Center for Biosimilars^®. March 4, 2025. Accessed March 9, 2025. https://www.centerforbiosimilars.com/view/fda-approves-third-pair-of-denosumab-biosimilars
4. FKS518 (denosumab). Biologics HQ. Updated February 28, 2025. Accessed March 9, 2025. https://biologicshq.com/product/fks518/
5. TVB-009P (denosumab). Biologics HQ. Updated February 28, 2025. Accessed March 9, 2025. https://biologicshq.com/product/tvb-009p/
6. HLX14 (denosumab). Biologics HQ. Updated February 28, 2025. Accessed March 9, 2025. https://biologicshq.com/product/hlx14/
7. INTP23 (denosumab). Biologics HQ. Updated February 28, 2025. Accessed March 9, 2025. https://biologicshq.com/product/intp23/
8. RGB-14 (denosumab). Biologics HQ. Updated February 28, 2025. Accessed March 9, 2025. https://biologicshq.com/product/rgb-14/
9. Morsali D, Schwarts RS. Amgen and Sandoz settle Prolia® / Xgeva® biosimilar litigation. Biologics HQ. April 30, 2024. Accessed March 9, 2025. https://biologicshq.com/amgen-and-sandoz-settle-prolia-xgeva-biosimilar-litigation/
10. Schwartz RS. Celltrion and Amgen Reach Settlement in Prolia® / Xgeva® Biosimilar Litigation. Biologics HQ. January 28, 2025. Accessed March 9, 2025. https://biologicshq.com/celltrion-and-amgen-reach-settlement-in-prolia-xgeva-biosimilar-litigation/
11. Remicade^® (infliximab). Biologics HQ. Updated February 28, 2025. Accessed March 9, 2025. https://biologicshq.com/product/remicade/
12. Sandoz reaches agreement with Amgen resolving all patent litigation related to its US denosumab biosimilars. Press release. Sandoz; April 30, 2024. Accessed March 9, 2025. https://www.sandoz.com/sandoz-reaches-agreement-amgen-resolving-all-patent-litigation-related-its-us-denosumab-biosimilars/
13. Amgen update on patent litigation related to Celltrion denosumab biosimilar products. Press release. Amgen; Accessed March 9, 2025. https://www.amgen.com/newsroom/company-statements/amgen-update-on-patent-litigation-related-to-celltrion-denosumab-biosimilar-products
14. Scheduling order for Civil No. 24-8417. The United States District Court for the District of New Jersey Camden Vicinage. November 6, 2024. Accessed March 9, 2025. https://biologicshq.com/wp-content/uploads/2025/03/SB-Scheduling-Order-2024-11-06-DNJ-1-24-cv-08417-58.pdf
15. Renflexis^® (infliximab-abda). Biologics HQ. Updated February 28, 2025. Accessed March 9, 2025. https://biologicshq.com/product/renflexis/