Tocilizumab

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 adopted positive opinions and recommended marketing authorisations for three biosimilar candidates: Eydenzelt ® (CT-P42, aflibercept), Stoboclo ® and Osenvelt ® (CT-P41, denosumab), and Avtozma ® (CT-P47, tocilizumab). This significant milestone reflects the company’s leadership in biosimilar innovation and commitment to expanding access to biologic treatments across Europe. Eydenzelt (40 mg/mL solution for injection in vial and pre-filled syringe), a biosimilar to Eylea ® (aflibercept), is recommended for approval to treat multiple retinal disorders, including neovascular (wet) age-related macular degeneration (AMD), macular edema following retinal vein occlusion (RVO, branch RVO or central RVO), diabetic macular edema (DME) and myopic choroidal neovascularisation (myopic CNV). In a Phase III study of Eydenzelt, the efficacy, safety, pharmacokinetics and immunogenicity of Eydenzelt was compared to Eylea in patients with diabetic macular edema (DME), demonstrating therapeutic equivalence to Eylea by meeting the predefined equivalence criteria. 1 If marketing authorisation is granted by the European Commission (EC), Eydenzelt would be one of the first-wave aflibercept biosimilars in Europe. Stoboclo (60 mg solution for injection in pre-filled syringe) and Osenvelt (120 mg solution for injection in vial) have been recommended for approval for all indications of the reference products Prolia ® and Xgeva ® , respectively. The positive CHMP opinion was based on the totality of evidence including results from a Phase III clinical trial in postmenopausal osteoporosis (PMO), and the results showed that CT-P41 had equivalent efficacy and pharmacodynamics (PD) to reference denosumab, with similar pharmacokinetics (PK) and comparable safety and immunogenicity profiles. 2 Avtozma , a biosimilar referencing RoActemra ® (tocilizumab), has been recommended for all indications of its reference product, including moderate to severely active rheumatoid arthritis (RA), active systemic juvenile idiopathic arthritis (sJIA), juvenile idiopathic polyarthritis (pJIA) and giant cell arteritis (GCA). The positive CHMP opinion for Avtozma was supported by a comprehensive data package and totality of evidence demonstrating Avtozma’s biosimilarity to RoActemra, with no clinically meaningful differences in efficacy, PK equivalence, safety or immunogenicity. 3,4 “ With CHMP approvals for Eydenzelt, Avtozma, and Prolia/Xgeva biosimilars, Celltrion solidifies its leadership in the European biosimilar market, offering one of the most extensive antibody biosimilar portfolios. Our vertically integrated model ensures supply chain stability while addressing the specific challenges faced by European healthcare professionals and patients. These approvals underscore our commitment to supporting European healthcare systems by improving access to high-quality, affordable treatments,” said Taehun Ha, Vice President and Head of Europe. “ Our focus remains on empowering clinicians with the tools and solutions they need, as we aim to transition from a pioneer to a frontier leader in European healthcare.” The CHMP’s recommendations will now be referred to the EC, which will decide whether to grant a marketing authorisation for Eydenzelt, Stoboclo and Osenvelt, and Avtozma. If marketing authorisations are granted, the three biosimilars will be made available across EU member states, furthering Celltrion’s commitment to delivering innovative and accessible healthcare solutions. About CT-P41 Phase III Clinical Trial The Phase III study randomised 479 patients to receive 60 mg of CT-P41 or reference product every six months (Weeks 0 and 26; treatment period [TP] I). Before dosing at Week 52, patients initially assigned to reference product in TP I were re-randomised in a 1:1 ratio 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 their treatment with CT-P41 in TP II. In TP II, 422 patients were randomised in Week 52 (CT-P41 maintenance group: 221, reference product maintenance group: 100, switched to CT-P41 group: 101). The primary efficacy endpoint was met in terms of percent change from baseline in bone mineral density (BMD) for lumbar spine (L1-L4) by dual-energy X-ray absorptiometry (DXA) at Week 52, and the primary pharmacodynamics (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 initial six months. Results of the study showed that CT-P41 had equivalent efficacy and PD to reference denosumab, with similar PK and comparable safety and immunogenicity profiles. 2 About CT-P42 Phase III Clinical Trial In a randomised, double-masked, parallel-group, multi-centre Phase III study of Eydenzelt ® (CT-P42), the efficacy, safety, pharmacokinetics, usability and immunogenicity of Eydenzelt was compared to Eylea ® (aflibercept) 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. Results of the study showed that Eydenzelt met the predefined equivalence criteria, and secondary endpoints of efficacy, safety, and immunogenicity also showed trends similar to Eylea. 1,5 About CT-P47 Phase III Clinical Trial This was a Phase III, randomised, active-controlled, double-blind trial to compare the efficacy and safety of Avtozma ® (CT-P47) and RoAtemra ® (tocilizumab) in patients with moderate to severely active rheumatoid arthritis (RA). The Phase III study randomised 479 patients to receive 8mg/kg of CT-P47 or reference tocilizumab every 4 weeks (Week 0 and 24; treatment period [TP] I). Before dosing at Week 24, patients initially assigned to tocilizumab in TP I were re-randomised in a 1:1 ratio to continue with tocilizumab or switch to CT-P47 in TP II up to Week 52. In TP II, 444 patients were randomised in Week 24 (CT-P47 maintenance group: 225, tocilizumab maintenance group: 109, switched to CT-P47 group: 110). The primary endpoint was mean change from baseline in Disease Activity score in 28 joints (DAS28; erythrocyte sedimentation rate [ESR]) at week 12. Efficacy equivalence was determined if confidence intervals (CIs) for the treatment difference was within the predefined equivalence margin: (95% CI: -0.6, +0.6 (analysis of covariance [ANCOVA]) at week 12). Therapeutic equivalence of CT-P47 and reference tocilizumab in treating RA was demonstrated and supported by comparable and sustained efficacy results up to Week 52. CT-P47 was also well tolerated with a safety profile comparable to reference tocilizumab, and no notable safety issue was identified following the single transition from reference tocilizumab to CT-P47 compared with 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 reference product Prolia ® (denosumab). In Europe, Stoboclo has been recommended for approval to treat osteoporosis in postmenopausal women and in men at increased risk of fractures, bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures, and 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 referencing Xgeva ® (denosumab). Osenvelt has been recommended for approval in Europe to prevent skeletal-related events in adults with advanced malignancies involving bone, and to treat adults and skeletally mature adolescents with giant cell tumour of bone that is unresectable or where surgical resection is likely to result in severe morbidity. About Eydenzelt ® (CT-P42, biosimilar candidate of aflibercept) Eydenzelt ® (aflibercept) is a vascular endothelial growth factor (VEGF) inhibitor referencing Eylea ® . Based on comprehensive data from a Phase III clinical trial confirming therapeutic equivalence to Eylea 1 , Eydenzelt was filed for regulatory approval with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) in June and November 2023, respectively. About Avtozma ® (CT-P47, biosimilar candidate of tocilizumab) CT-P47, containing the active ingredient tocilizumab, is a recombinant humanised 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 , CT-P47 was filed for regulatory approval with the U.S. FDA and EMA in January and February 2024, respectively. About Celltrion Celltrion is a leading biopharmaceutical company based in Incheon, South Korea that specialises in researching, developing, manufacturing, marketing and sales of innovative therapeutics that improve people's lives worldwide. The company’s solutions include world-class monoclonal antibody biosimilars such as Remsima ® , Truxima ® and Herzuma ® , providing broader patient access globally. Celltrion has also received U.S. FDA and EC approval for Vegzelma ® and Yuflyma ® , FDA approval for Zymfentra ® , and EC approval for Remsima ® SC, Omlyclo ® , SteQeyma ® . To learn more, please visit www.celltrion.com/en-us . FORWARD-LOOKING STATEMENT Certain information set forth in this press release contains statements related to our future business, and financial performance and future events or developments involving Celltrion Inc. and its subsidiaries that may constitute forward-looking statements, under pertinent securities laws. These statements may be identified by words such as “prepares,” “hopes to,” “upcoming,” ”plans to,” “aims to,” “to be launched,” “is preparing,” “once gained,” “could,” “with the aim of,” “may,” “once identified,” “will,” “working towards,” “is due,” “become available,” “has potential to,” the negative of these words or such other variations thereon or comparable terminology. In addition, our representatives may make oral forward-looking statements. Such statements are based on the current expectations and certain assumptions of Celltrion Inc. and its subsidiaries' management, of which many are beyond its control. Forward-looking statements are provided to allow potential investors the opportunity to understand management’s beliefs and opinions in respect of the future so that they may use such beliefs and opinions as one factor in evaluating an investment. These statements are not guarantees of future performance and undue reliance should not be placed on them. Such forward-looking statements necessarily involve known and unknown risks and uncertainties, which 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 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]. Available at: https://abstracts.euretina.org/2024/ca24-2257-8397/r/recxUD7DqYfFfjC7s [Last accessed December 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. Available at: https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/39042292/ [Last accessed December 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. Available at: https://rmdopen-bmj-com.libproxy1.nus.edu.sg/content/10/4/e004514.abstract [Last accessed December 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. Poster Presentation (abstract no. 0502). Presented at ACR 2024. Available at: 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/ [Last accessed December 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. Available at: https://www-sciencedirect-com.libproxy1.nus.edu.sg/science/article/pii/S2468653024003063 [Last accessed December 2024].

Additional new profiling of patient responses from the optimized lymphodepletion arm (Arm C) show consistent P-BCMA-ALLO1 cellular expansion and persistence across subgroups New preclinical data supports P-CD19CD20-ALLO1’s strong anti-cancer profile and the ongoing Phase 1 clinical trial Case study demonstrates reactivation of an autologous Poseida CAR-T therapy with a T-cell engager in patient with relapsed multiple myeloma, highlighting potential of T SCM -based CAR-T therapies to deliver a strong anti-myeloma response with long-term remission and CAR-T cell persistence SAN DIEGO, CA, USA I December 9, 2024 I Poseida Therapeutics, Inc. (Nasdaq: PSTX ), a clinical-stage allogeneic cell therapy and genetic medicines company advancing differentiated non-viral treatments for patients with cancer, autoimmune and rare diseases, today will highlight interim clinical data from its Phase 1 trial of P-BCMA-ALLO1 in patients with relapsed/refractory multiple myeloma (RRMM), including new profiling of patient responses from Arm C, an optimized lymphodepletion arm. The P-BCMA-ALLO1 data are being presented, along with two additional Company poster presentations covering new preclinical data for P-CD19CD20-ALLO1 and a patient case study demonstrating the reactivation of a Poseida autologous CAR-T therapy with a T-cell engager, at the 66 th ASH Annual Meeting and Exposition being held in San Diego on December 7-10, 2024. P-BCMA-ALLO1 is an investigational non-viral, stem cell memory T cell (T SCM )-rich allogeneic CAR-T cell therapy in Phase 1/1b clinical development for the treatment of patients with RRMM. P-CD19CD20-ALLO1 is an investigational, non-viral T SCM -rich allogeneic CAR-T cell therapy in Phase 1 clinical development for the treatment of patients with B-cell malignancies and is the Company’s first dual CAR-T program. P-BCMA-ALLO1 and P-CD19CD20-ALLO1 are being developed in collaboration with Roche. “We continue to gain confidence in the potential for P-BCMA-ALLO1 in multiple myeloma, including from the additional sub-analysis of the Phase 1 data presented at ASH,” said Kristin Yarema, Ph.D., President and Chief Executive Officer of Poseida Therapeutics. “We believe the data to-date provide strong validation for our allogeneic cell therapy platform, laying the groundwork for us to extend our non-viral, T SCM -rich approach and drive value with additional clinical programs. This includes P-CD19CD20-ALLO1, our first dual CAR-T supported by preclinical data presented at ASH, and with clinical data anticipated in 2025.” P-BCMA-ALLO1 Phase 1 Data The poster presentation will highlight Phase 1 clinical data first presented at the 21 st International Myeloma Society (IMS) Annual Meeting in September 2024. The data showed a 91% overall response rate (ORR) in Arm C (an optimized lymphodepletion arm), including a 100% ORR in B-cell maturation antigen (BCMA)-naïve patients, and an 86% ORR in those who had received at least one prior BCMA- and/or G protein-coupled receptor class C group 5 member D (GPRC5D)-targeting treatment modality, along with differentiated safety results with no dose-limiting toxicities, low rates of cytokine release syndrome (CRS) and immune effector cell neurotoxicity syndrome (ICANS), all Grade 2 or less, and no graft vs. host disease or Parkinsonism. No patients required anti-myeloma bridging therapy or prophylaxis with steroids or tocilizumab, and there was no invasive apheresis; an average manufacturing wait time, from treatment decision to clinical response, was only 3.5 weeks 1 (with a median time to response of 16 days post initial P-BCMA-ALLO1 therapy). The patients in this study had more advanced disease than the myeloma patients studied in clinical trials of approved autologous CAR-T therapies 2 , and in the intent-to-treat population, 100% of patients were infused with P-BCMA-ALLO1. New profiling of patient responses from Arm C are included in the ASH poster presentation. The data from this analysis show consistent P-BCMA-ALLO1 cellular expansion and persistence across different subgroups, including patients that are typically more challenging to treat. Key highlights suggest that P-BCMA-ALLO1: P-CD19CD20-ALLO1 Preclinical Data Preclinical data has demonstrated that P-CD19CD20-ALLO1 delivers high in vitro potency and strong in vivo antitumor activity for either CD19 or CD20 single-positive target cells, as well as double-positive targets. New preclinical data included in the poster presentation show that compared to CD19-single targeting or CD20-single targeting CAR-T cells, P-CD19CD20-ALLO1: The Company’s P-CD19CD20-ALLO1 Phase 1 clinical trial is enrolling patients with selected B-cell malignancies, with initial clinical data anticipated in 2025. CAR-T Reactivation with T-cell Engager Case Study The case study highlights the reactivation of an autologous Poseida CAR-T therapy with a T-cell engager in a patient with relapsed multiple myeloma. The patient attained and remained in stringent complete response over 12 months after CAR-T reactivation. This case highlights the potential of Poseida’s T SCM -based CAR-T therapies to deliver a strong anti-myeloma response with long-term remission and CAR-T cell persistence. The Company believes this is the first time that a T-cell engager has been seen to reactivate a CAR-T therapy. ASH 2024 Poster Presentations Title: Late Polyclonal P-BCMA-101 CAR-T Cell Re-expansion and Rapid Complete Response in a Patient with Relapsed Multiple Myeloma Treated with One Cycle of Talquetamab, More Than 3 Years After CAR-T Infusion Title: P-CD19CD20-ALLO1: Potent Fully Allogeneic CAR-T Therapy Targeting CD19 and CD20 with Superior Efficacy Over Single-Target Products Title: A Phase 1 Study of P-BCMA-ALLO1, a Non-viral, Allogeneic BCMA Directed CAR-T in Relapsed/Refractory Multiple Myeloma (RRMM): Results from Optimized Lymphodepletion Cohort About P-BCMA-ALLO1 P-BCMA-ALLO1 is an allogeneic CAR-T product candidate licensed to Roche targeting B-cell maturation antigen (BCMA) for the treatment of relapsed/refractory multiple myeloma. This allogeneic program includes a VH-based binder that targets BCMA, and interim clinical data presented at IMS in September 2024 support the Company’s belief that T stem cell (T SCM )-rich allogeneic CAR-Ts have the potential to offer effective, safe and reliable treatment addressing unmet needs in multiple myeloma. The FDA has granted P-BCMA-ALLO1 Orphan Drug designation for multiple myeloma and Regenerative Medicine Advanced Therapy (RMAT) designation for adult patients with relapsed/refractory multiple myeloma after three or more prior lines of therapies including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody. P-BCMA-ALLO1 is currently being evaluated in a Phase 1/1b trial in patients with multiple myeloma. Additional information about the trial is available at www.clinicaltrials.gov using identifier: NCT04960579. About P-CD19CD20-ALLO1 P-CD19CD20-ALLO1 is an allogeneic CAR-T cell therapy product candidate being developed for relapsed or refractory B-cell malignancies in partnership with Roche. P-CD19CD20-ALLO1 expresses two fully functional CAR molecules to target cells that express either CD19 or CD20. The dual targeting approach employed in P-CD19CD20-ALLO1 aims to overcome the antigen escape limitations of CD19-only targeted CAR-T therapies by simultaneously targeting both CD19 and CD20. In addition to the dual targeting, P-CD19CD20-ALLO1 uses a novel CD19 binder that showed greater potency in in vivo preclinical models when compared to the canonical FMC63 Single-chain variable fragment (scFv) binder. P-CD19CD20-ALLO1 is an off-the-shelf CAR-T therapy for which patients do not have to undergo apheresis and wait for cells to be manufactured, which can potentially overcome the limitation of autologous CAR-T therapies associated with significant manufacturing times. P-CD19CD20-ALLO1 is being studied in a Phase 1 study in B-cell malignancies ( www.clinicaltrials.gov using identifier: NCT06014762). Building on the transformative potential of the CAR-T modality beyond oncology, the Company has recently submitted investigational new drug (IND) applications to the U.S. Food and Drug Administration (FDA) to investigate this program’s potential for patients with multiple sclerosis and systemic lupus erythematosus. About Poseida Therapeutics, Inc. Poseida Therapeutics is a clinical-stage biopharmaceutical company advancing differentiated allogeneic cell therapies and genetic medicines with the capacity to cure. The Company’s pipeline includes investigational allogeneic CAR-T cell therapies for hematologic cancers, autoimmune diseases, and solid tumors, as well as investigational in vivo genetic medicines that address patient populations with high unmet medical need. The Company’s approach is based on its proprietary genetic editing platforms, including its non-viral transposon-based DNA delivery system, Cas-CLOVER™ Site-Specific Gene Editing System, Booster Molecule and nanoparticle gene delivery technologies, as well as in-house GMP cell therapy manufacturing. The Company has formed strategic collaborations with Roche and Astellas to unlock the promise of cell therapies for cancer patients. Learn more at www.poseida.com and connect with Poseida on X and LinkedIn . 1 Based on interim data from Phase 1 P-BCMA-ALLO1 clinical trial announced in September 2024, Arms A and B. 2 No head-to-head trial has been conducted evaluating P-BCMA-ALLO1 against other products included herein. Cross-trial data interpretation should be considered with caution as it is limited by differences in study population, study design, and other factors. SOURCE: Poseida Therapeutics, Inc.