Celltrion receives positive CHMP recommendation for approval of three biosimilars in the European Union

Celltrion’s three biosimilar candidates – Eydenzelt ^® (aflibercept), Stoboclo ^® , Osenvelt ^® (denosumab) and Avtozma ^® (tocilizumab) – receive the positive recommendation for approval from the Committee for Medicinal Products for Human Use (CHMP)
Celltrion is committed to improving access to biologic treatments for bone diseases, ophthalmology and immunology

INCHEON, South Korea–( BUSINESS WIRE )–Celltrion today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended marketing authorization for three biosimilar candidates: Eydenzelt ^® (CT-P42, aflibercept), Stoboclo ^® , Osenvelt ^® (CT-P41, denosumab) and Avtozma ^® (CT-P47, tocilizumab). This significant milestone demonstrates the company’s leadership in biosimilar innovation and commitment to improving access to biologics treatments across Europe.

Eydenzelt (40 mg/ml solution for injection in a vial and pre-filled syringe), a biosimilar to Eylea ^® (aflibercept), is recommended for approval for the treatment of various retinal diseases, including neovascular (wet) age-related macular degeneration (AMD), macular edema following retinal vein occlusion (RVO, branch RVO or central retinal vein occlusion), diabetic macular edema (DME) and myopic choroidal neovascularization (myopic CNV). In a Phase III study by Eydenzelt, the efficacy, safety, pharmacokinetics and immunogenicity of Eydenzelt were compared with Eylea in patients with diabetic macular edema (DME) and therapeutic equivalence to Eylea was demonstrated because the predefined equivalence criteria were met. ¹ If the European Commission (EC) grants marketing authorisation, Eydenzelt would be one of the first aflibercept biosimilars in Europe.

Stoboclo (60 mg solution for injection in a pre-filled syringe) and Osenvelt (120 mg solution for injection in a vial) were recommended for approval for all indications of the reference products Prolia ^® and Xgeva ^® respectively. The CHMP’s recommendation for approval was based on the comprehensive evidence from all clinical studies, including the results of a Phase III clinical study in postmenopausal osteoporosis (PMO). The results showed that CT-P41 had equivalent efficacy and pharmacodynamics (PD) to the reference product denosumab, with similar pharmacokinetics (PK) and comparable safety and immunogenicity profiles. ²

Avtozma , a biosimilar to RoActemra ^® (tocilizumab), was recommended for all indications of the reference product, including moderate to severe active rheumatoid arthritis (RA), active systemic juvenile idiopathic arthritis (sJIA), juvenile idiopathic polyarthritis (pJIA) and giant cell arteritis (GCA). The CHMP recommendation to approve Avtozma was supported by the comprehensive evidence from the data package submitted for approval, which demonstrated the biosimilarity of Avtozma to RoActemra. There were no clinically meaningful differences in efficacy, PK equivalence, safety or immunogenicity. ^3,4

” With the CHMP approval recommendations for the biosimilars Eydenzelt, Avtozma and Stoboclo/Osenvelt, Celltrion consolidates its leadership position in the European biosimilar market and offers one of the most comprehensive portfolios of antibody biosimilars. Our vertically integrated organization ensures supply chain stability while addressing the specific challenges faced by physicians and patients in Europe. These approval recommendations underline our commitment to supporting European healthcare systems by improving access to high-quality and affordable treatments,” said Taehun Ha, Vice President and Head of Europe. ” Our focus remains on providing physicians with the tools and solutions they need. We are committed to moving from pioneer to leader in European healthcare.”

The CHMP’s recommendations will now be forwarded to the European Commission, which will decide whether to grant marketing authorisation for Eydenzelt, Stoboclo and Osenvelt, and Avtozma. If the marketing authorisations are granted, the three biosimilars will be available in all EU member states. Celltrion remains committed to making innovative biosimilars available and improving access to innovative therapies in the future.

About the Phase III clinical trial with CT-P41

In the Phase III study, 479 patients were randomized to receive 60 mg CT-P41 or the reference product every six months (weeks 0 and 26; treatment period [TP] I). Prior to dosing at week 52, patients initially assigned to the reference product in TP I were re-randomized 1:1 to continue with the reference product or switch to CT-P41 in TP. All patients initially randomly assigned to CT-P41 in TP I continued treatment with CT-P41 in TP II. In TP II, 422 patients were randomized at week 52 (CT-P41 maintenance group: 221, reference product maintenance group: 100, CT-P41 switch group: 101). The primary efficacy endpoint was met in terms of percent change from baseline in lumbar spine (L1-L4) bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) at week 52, and the primary pharmacodynamic (PD) endpoint was met in terms of area under the effect curve (AUEC) of serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTX) over the first six months. The results of the study showed that CT-P41 had equivalent efficacy and PD to the reference drug denosumab, with similar PK and comparable safety and immunogenicity profiles. ²

About the Phase III clinical trial with CT-P42

In a randomized, double-blind, parallel, multicenter Phase III study of Eydenzelt ^® (CT-P42), the efficacy, safety, pharmacokinetics, applicability and immunogenicity of Eydenzelt with Eylea ^® (aflibercept) were compared in patients with diabetic macular edema (DME). The primary endpoint was the change from baseline in best-corrected visual acuity (BCVA) measured at week 8, comparing Eydenzelt and Eylea. The results of the study showed that Eydenzelt met the predefined equivalence criteria, and the secondary endpoints of efficacy, safety and immunogenicity also showed similar trends to Eylea. ^1,5

About the Phase III clinical trial with CT-P47

This was a randomized, active-controlled, double-blind Phase III study to compare the efficacy and safety of Avtozma ^® (CT-P47) and RoAtemra ^® (tocilizumab) in patients with moderately to severely active rheumatoid arthritis (RA). In the Phase III study, 479 patients were randomized to receive 8 mg/kg CT-P47 or the reference drug tocilizumab every 4 weeks (Weeks 0 and 24; Treatment Period [BP] I). Prior to dosing at Week 24, patients originally assigned to tocilizumab in TP I were re-randomized 1:1 to continue with tocilizumab or to switch to CT-P47 in TP II by Week 52. In TP II, 444 patients were randomized at week 24 (CT-P47 maintenance group: 225, tocilizumab maintenance group: 109, CT-P47 switched group: 110). The primary endpoint was the mean change from baseline in disease activity score in 28 joints (DAS28; erythrocyte sedimentation rate [ESR]) at week 12. Efficacy equivalence was established if the confidence intervals (CIs) for the treatment difference were within the predefined equivalence range: (95% CI: -0.6, +0.6 (ANCOVA analysis) at week 12). The therapeutic equivalence of CT-P47 and the reference tocilizumab in the treatment of RA was demonstrated and supported by comparable and sustained efficacy results through week 52. CT-P47 was also well tolerated and had a safety profile comparable to that of the reference product, tocilizumab. After the one-time crossover from tocilizumab to the reference product to CT-P47, no significant safety issues were observed compared to the maintenance groups up to week 52. ^3,4

About Stoboclo ^® (CT-P41, biosimilar candidate of denosumab)

Stoboclo ^® (denosumab), a receptor activator of NF-κb ligand (RANKL) inhibitor, is a treatment developed as a biosimilar to the reference product Prolia ^® (denosumab). In Europe, Stoboclo has been recommended for the treatment of osteoporosis in postmenopausal women and in men at increased risk of fracture, in bone loss associated with hormone ablation in men with prostate cancer at increased risk of fracture, and in bone loss associated with long-term systemic glucocorticoid therapy in adult patients at increased risk of fracture.

About Osenvelt ^® (CT-P41, biosimilar candidate of denosumab)

Osenvelt ^® (denosumab) is a receptor activator of NF-κb ligand (RANKL) inhibitor developed as a biosimilar to Xgeva ^® (denosumab). Osenvelt has been recommended for approval in Europe to prevent skeletal-related events in adults with advanced malignant bone disease and to treat skeletally mature adults and adolescents with unresectable giant cell tumor of bone or when surgical resection would likely result in severe morbidity.

About Eydenzelt ^® (CT-P42, biosimilar candidate of aflibercept)

Eydenzelt ^® (aflibercept) is a vascular endothelial growth factor (VEGF) inhibitor referenced to Eylea ^® . Based on comprehensive data from a Phase III clinical trial confirming therapeutic equivalence to Eylea ¹ , Eydenzelt has been submitted for regulatory approval to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in June and November 2023, respectively.

About Avtozma ^® (CT-P47, biosimilar candidate of tocilizumab)

CT-P47, which contains the active ingredient tocilizumab, is a recombinant humanized monoclonal antibody that acts as an interleukin-6 (IL-6) receptor antagonist. Based on data from the global Phase III clinical trial designed to evaluate the efficacy, pharmacokinetics (PK), safety and immunogenicity of CT-P47 compared to the reference product RoActemra ^®4 , regulatory approval of CT-P47 was submitted to the US FDA and EMA in January and February 2024, respectively.

About Celltrion

Celltrion is a leading biopharmaceutical company based in Incheon, South Korea, focused on discovering, developing, manufacturing, commercializing and distributing innovative therapeutics that improve the lives of people worldwide. The company’s solutions include best-in-class monoclonal antibody biosimilars such as Remsima ^® , Truxima ^® and Herzuma ^® , enabling broader access to patients worldwide. Celltrion has also received U.S. FDA and European Commission approval for Vegzelma ^® and Yuflyma ^® , FDA approval for Zymfentra ^® and European Commission approval for Remsima ^® SC, Omlyclo ^® , SteQeyma ^® . For more information, visit www.celltrion.com/en-us .

FORWARD-LOOKING STATEMENT

Certain information contained in this press release contains statements regarding our future business, financial performance and future events or developments affecting Celltrion Inc. and its subsidiaries that may constitute forward-looking statements under applicable securities laws.

These statements can be identified by words such as “prepares,” “hopes to,” “pending,” “plans,” “aims,” ”will be launched,” “is preparing,” “once won,” “could,” “with the aim of,” “may,” “once identified,” “will,” “work toward,” “is due,” “will be available,” “has the potential to,” the negative of these words or other variations thereof or comparable terminology.

In addition, our representatives may make oral forward-looking statements. Such statements are based on the current expectations and various assumptions of the management of Celltrion and its subsidiaries, many of which are beyond the control of the Company.

Forward-looking statements are made to provide prospective investors with an opportunity to understand management’s beliefs and opinions regarding the future so that they may use those beliefs and opinions as a factor in evaluating an investment. These statements are not guarantees of future performance and should not be unduly relied upon.

Such forward-looking statements necessarily involve known and unknown risks and uncertainties that may cause actual performance and financial results in future periods to differ materially from any projections of future performance or results expressed or implied by such forward-looking statements.

Celltrion Inc. and its subsidiaries undertake no obligation to update any forward-looking statements if circumstances or management’s estimates or opinions should change, except as required by applicable securities laws.

trademark

Stoboclo ^® and Osenvelt ^® are registered trademarks of Celltrion Inc.
Prolia ^® and Xgeva ^® are registered trademarks of Amgen Inc.

Eydenzelt ^® is a registered trademark of Celltrion Inc.
Eylea ^® is a registered trademark of Bayer AG.

Avtozma ^® is a registered trademark of Celltrion, Inc. used under license.
RoActemra ^® is a registered trademark of Chugai Pharmaceutical Co., Ltd.

references

¹ Sebastian Wolf et al., Long-term efficacy and Safety of CT-P42 compared to Reference Aflibercept in Diabetic Macular Edema: 52-Week Results from the Phase 3 CT-P42 3.1. [EURETINA 2024, Abstract #CA24-2257-8397]. Verfügbar unter: https://abstracts.euretina.org/2024/ca24-2257-8397/r/recxUD7DqYfFfjC7s [Zuletzt abgerufen im Dezember 2024].
² Reginster JY et al. Efficacy and safety of candidate biosimilar CT-P41 versus reference denosumab: a double-blind, randomized, active-controlled, Phase 3 trial in postmenopausal women with osteoporosis. Osteoporos Int. 2024 Nov;35(11):1919-1930. doi: 10.1007/s00198-024-07161-x. Epub 2024 Jul 23. PMID: 39042292; PMCID: PMC11499533. Verfügbar unter: https://pubmed.ncbi.nlm.nih.gov/39042292/ [Zuletzt abgerufen im Dezember 2024].
³ Smolen JS et al., Efficacy and safety of CT-P47 versus reference tocilizumab: 32-week results of a randomised, active-controlled, double-blind, phase III study in patients with rheumatoid arthritis, including 8 weeks of switching data from reference tocilizumab to CT-P47. RMD Open. 2024;10(4), e004514. Verfügbar unter: https://rmdopen.bmj.com/content/10/4/e004514.abstract [Zuletzt abgerufen im Dezember 2024].
⁴ Gerd Burmester et al., Similar Efficacy, PK, Safety, and Immunogenicity of Tocilizumab Biosimilar (CT-P47) and Reference Tocilizumab in Patients with Moderate-to-Severe Active Rheumatoid Arthritis: Week 52 Results from the Phase III Single Transition Study. Posterpräsentation (Abstract Nr. 0502). Präsentiert auf der ACR 2024. Verfügbar unter: https://acrabstracts.org/abstract/similar-efficacy-pk-safety-and-immunogenicity-of-tocilizumab-biosimilar-ct-p47-and-reference-tocilizumab-in-patients-with-moderate-to-severe-active-rheumatoid-arthritis-week-52-results-from-the/ [Zuletzt abgerufen im Dezember 2024].
⁵ Sebastian Wolf et al., Biosimilar Candidate CT-P42 in Diabetic Macular Edema: 24-Week Results from a Randomized, Active-Controlled, Phase III Study. Verfügbar unter: https://www.sciencedirect.com/science/article/pii/S2468653024003063 [Zuletzt abgerufen im Dezember 2024].

The source language in which the original text is published is the official and authorized version. Translations are provided for ease of understanding. Only the language version that was originally published is legally binding. Therefore, compare translations with the original language version of the publication.