Fourth Ustekinumab Biosimilar, Otulfi, Approved in US

The FDA has approved the fourth ustekinumab biosimilar, ustekinumab-aauz (Otulfi) from Formycon and Fresenius Kabi, referencing Stelara (Johnson & Johnson [J&J]).¹ The approval covers Crohn disease, ulcerative colitis, moderate to severe plaque psoriasis, and active psoriatic arthritis. Ustekinumab is a human monoclonal antibody targeting IL-12 and IL-23.

The biosimilar was approved at the same time in the European Union.²

“The U.S. approval is an important step on our path to sustainable profitability, since FYB202 will contribute strongly to the financial strength of Formycon,” Enno Spillner, chief financial officer of Formycon AG, said in a statement.¹ “We are pleased that with the recent approval decisions of the European Commission and the FDA, we have now successfully completed the formal approval process of FYB202 for the major markets.”

Due to settlements reached earlier in the year, Otulfi will not be able to launch until February 22, 2025.³ The other approved biosimilars for ustekinumab will also wait until 2025 to launch. The first ustekinumab biosimilar, Wezlana from Amgen, was approved November 1, 2023, with an interchangeability designation and will launch “no later than January 1, 2025,” according to the settlement with J&J.^4,5

Wezlana was followed by Alvotech’s Selarsdi and Samsung Bioepis’ Pyzchiva.^6,7 Pyzchiva was also granted the interchangeability designation.

Formycon acquired the rights to Otulfi in 2022, when it also acquired FYB201, which references Lucentiz (ranibizumab), used to treat ophthalmic conditions, including neovascular (or wet) age-related macular degeneration, macular edema, and diabetic retinopathy.⁸

Stelara first launched in 2009 with sales reaching $10.8 billion in worldwide sales in 2023 and around $6 billion in the US.^1,9

Clinical data on Otulfi were presented at the European Academy of Dermatology & Venerology meeting, held September 25-28 in Amsterdam, the Netherlands. The results of the VESPUCCI trial, a multicenter, phase 3 study, showed Otulfi met the primary end point, demonstrating similar efficacy of the biosimilar and the reference product in patients with moderate to severe plaque psoriasis.¹⁰

Separately, the RUSTCI trial demonstrated pharmacokinetic similarity between Otulfi and Stelara in 491 healthy adults, who were observed for up to 112 days.¹¹ There were no clinically meaningful differences with overall safety, immunogenicity, and local tolerability and fewer subjects receiving the biosimilar had at least 1 positive antidrug antibody result compared with the reference product.

References

1. Formycon and Fresenius Kabi receive FDA approval for FYB202/Otulfi (ustekinumab-aauz). Formycon. September 30, 2024. Accessed September 30, 2024. https://www.formycon.com/en/blog/press-release/fda-grants-approval-for-stelara-biosimilar-fyb202-otulfitm-ustekinumab-aauz/

2. Formycon and Fresenius Kabi receive European Commission approval for FYB202/Otulfi (ustekinumab) for the treatment of serious inflammatory diseases. News release. Formycon. September 27, 2024. Accessed September 30, 2024. https://www.formycon.com/en/blog/press-release/formycon-and-fresenius-kabi-receive-european-commission-approval-for-fyb202-otulfi-ustekinumab-for-the-treatment-of-serious-inflammatory-diseases/

3. Zamecnik A. J&J signs Stelara biosimilar settlement deal with Formycon and Fresenius. Pharmaceutical Technology. August 8, 2023. Accessed September 30, 2024. https://www.pharmaceutical-technology.com/news/jj-signs-stelara-biosimilar-settlement-deal-formycon-fresenius

4. Jeremias S. FDA approves first Stelara biosimilar, Wezlana. The Center for Biosimilars^®. November 1, 2023. Accessed September 30, 2024. https://www.centerforbiosimilars.com/view/fda-approves-first-stelara-biosimilar-wezlana

5. Jeremias S. Amgen’s Stelara biosimilar delayed until 2025 after settling with J&J. The Center for Biosimilars. May 29, 2023. Accessed September 30, 2024. https://www.centerforbiosimilars.com/view/amgen-s-stelara-biosimilar-delayed-until-2025-after-settling-with-j-j

6. Jeremias S. Alvotech’s Stelara biosimilar, Selarsdi, receives FDA approval. The Center for Biosimilars. April 16, 2024. Accessed September 30, 2024. https://www.centerforbiosimilars.com/view/alvotech-s-stelara-biosimilar-selarsdi-receives-fda-approval

7. Jeremias S. FDA approves Samsung Bioepis’ Pyzchiva, a biosimilar to Stelara. The Center for Biosimilars. July 1, 2024. Accessed September 30, 2024. https://www.centerforbiosimilars.com/view/fda-approves-samsung-bioepis-pyzchiva-a-biosimilar-to-stelara

8. Formycon acquires assets for biosimilars referencing Lucentis, Stelara. The Center for Biosimilars. April 6, 2022. Accessed September 30, 2024. https://www.centerforbiosimilars.com/view/formycon-acquires-assets-for-biosimilars-referencing-lucentis-stelara

9. Becker Z, Liu A, Dunleavy K, Kansteiner F, Sagonowsky E. The top 20 drugs by worldwide sales in 2023. Fierce Pharma. May 28, 2024. Accessed September 30, 2024. https://www.fiercepharma.com/special-reports/top-20-drugs-worldwide-sales-2023

10. Formycon will present clinical data on its ustekinumab biosimilar candidate FYB202 at the EADV Congress in Amsterdam and the UEG Week in Vienna. News release. Formycon. September 17, 2024. Accessed September 30, 2204. https://www.formycon.com/en/blog/press-release/formycon-will-present-clinical-data-on-its-ustekinumab-biosimilar-candidate-fyb202-at-the-eadv-congress-in-amsterdam-and-the-ueg-week-in-vienna/

11. Balser S, Nopora K, Körner J, Wedemeyer R-S, Anschütz M, Schug B. New ustekinumab biosimilar candidate FYB202: pharmacokinetic equivalence demonstrated in a randomized, double-blind, parallel-group, single-dose trial in healthy subjects. Clin Pharmacol Drug Dev. Published online September 19, 2024. doi:10.1002/cpdd.1473