Avtozma (tocilizumab-anoh) / Celltrion - LARVOL DELTA

Celltrion Receives EC Approval for Avtozma (CT-P47), a Biosimilar to RoActemra (tocilizumab) (Businesswire) - "Celltrion today announced that the European Commission (EC) has granted marketing authorization for Avtozma (CT-P47), a biosimilar referencing RoActemra (tocilizumab). Avtozma has been approved for all indications of its reference product, including moderate to severely active rheumatoid arthritis (RA), active systemic juvenile idiopathic arthritis (sJIA), polyarticular juvenile idiopathic arthritis (pJIA) and giant cell arteritis (GCA)....The EC approval on Avtozma was supported by a comprehensive data package and totality of evidence, including the results from a phase III study demonstrating biosimilarity between Avtozma and the reference product."

EMA approval • Giant Cell Arteritis • Idiopathic Arthritis • Rheumatoid Arthritis

Celltrion secures approval for Actemra biosimilar SC form in Korea (Korea Biomedical Review) - "Celltrion said it obtained product approval from the Ministry of Food and Drug Safety (MFDS) for the subcutaneous (SC) formulation of Avtozma, a biosimilar referencing Actemra (ingredient: tocilizumab), for the treatment of autoimmune diseases....The Korean regulator approved the SC form based on the results of a global phase 3 clinical trial."

Korea approval • Immunology

U.S. FDA approves Celltrion's AVTOZMA (tocilizumab-anoh), a biosimilar to ACTEMRA (PRNewswire) - "Celltrion...announced that the U.S. Food and Drug Administration (FDA) has approved AVTOZMA (CT-P47, tocilizumab-anoh) in both an intravenous (IV) and subcutaneous (SC) formulation as a biosimilar to ACTEMRA. AVTOZMA is indicated for the treatment of multiple diseases including rheumatoid arthritis (RA), giant cell arteritis (GCA), polyarticular juvenile idiopathic arthritis (pJIA), systemic juvenile idiopathic arthritis (sJIA) and coronavirus disease (COVID-19)....The FDA's decision is based on a comprehensive data package and the totality of evidence, including the results from a phase III study demonstrating biosimilarity between AVTOZMA and reference tocilizumab in patients with moderate to severe active RA....The clinical results demonstrated that AVTOZMA and its reference tocilizumab are highly similar and have no clinically meaningful differences in terms of efficacy, safety, pharmacokinetics (PK) and immunogenicity."

FDA approval • Giant Cell Arteritis • Idiopathic Arthritis • Novel Coronavirus Disease • Rheumatoid Arthritis

Usability, efficacy, and safety of candidate tocilizumab biosimilar CT-P47 self-administration via auto-injector and pre-filled syringe in patients with rheumatoid arthritis: a single-arm, open-label, phase 3 study. (PubMed, Expert Rev Clin Immunol) - P3 | "CT-P47 self-administered using an AI showed successful usability in patients with moderate-to-severe RA. ClinicalTrials.gov identifier: NCT05725434."

Journal • P3 data • Hematological Disorders • Immunology • Inflammatory Arthritis • Leukopenia • Neutropenia • Rheumatoid Arthritis • Rheumatology

Celltrion’s Actemra biosimilar wins approval in Korea (Korea Biomedical Review) - "Celltrion said Monday that its biosimilar for Roche's autoimmune disease treatment Actemra (tocilizumab), branded as Avtozma (development code: CT-P47), has received approval from the Ministry of Food and Drug Safety in Korea. Celltrion said Monday that its biosimilar for Roche's autoimmune disease treatment Actemra (tocilizumab), branded as Avtozma (development code: CT-P47), has received approval from the Ministry of Food and Drug Safety in Korea."

Korea approval • Idiopathic Arthritis • Immunology • Rheumatoid Arthritis

Celltrion Receives Positive CHMP Opinion for Three Biosimilars in the European Union (Businesswire) - "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...biosimilar candidate...Avtozma (CT-P47, tocilizumab)....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."

CHMP • Giant Cell Arteritis • Idiopathic Arthritis • Rheumatoid Arthritis

Celltrion presents phase III data supporting biosimilarity of...CT-P47 at ACR Convergence 2024 (MedigateNews) - P3 | N=471 | NCT05489224 | Sponsor: Celltrion | "...Celltrion presented additional data...for CT-P47, a biosimilar candidate referencing ACTEMRA (tocilizumab) in patients with moderate-to-severe active rheumatoid arthritis (RA) at the American College of Rheumatology (ACR) Convergence 2024 in Washington, D.C....Results of the single transition from the reference tocilizumab to CT-P47 from a Phase III RCT were also presented at the ACR. The 1-year results showed that CT-P47 had comparable and sustained efficacy, safety and immunogenicity profiles in patients with active moderate-to-severe rheumatoid arthritis (RA) compared to the reference tocilizumab even after switching. These data further support biosimilarity of CT-P47."

P3 data • Immunology • Rheumatoid Arthritis

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 (ACR Convergence 2024) - "The study showed that CT-P47 was well tolerated over 1 year in patients with RA, with comparable efficacy, PK, safety, and immunogenicity to those of ref-tocilizumab. In addition, the efficacy has been sustained after switching from ref-tocilizumab to CT-P47 and no notable safety issue was identified following single transition."

Clinical • P3 data • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Celltrion's biosimilar CT-P47 demonstrates equivalence to Actemra in P3 study (Korea Biomedical Review) - P3 | N=471 | NCT05489224 | Sponsor: Celltrion | "Celltrion said the phase 3 clinical trial results CT-P47, a biosimilar referencing Roche’s Actemra (ingredient: tocilizumab), have been published in Rheumatic & Musculoskeletal Disease (RMD Open)....The results showed no significant difference between CT-P47 and Actemra, confirming that CT-P47 met the predefined equivalence criteria for efficacy, pharmacokinetics, and safety compared to the reference drug. At the 24-week mark, patients in the Actemra group were randomly assigned to either continue Actemra or switch to CT-P47 in a 1:1 ratio. Between weeks 24 and 32, efficacy, pharmacokinetics, safety, and immunogenicity were evaluated across three groups: patients who continued Actemra, those who switched to CT-P47, and those who had been receiving CT-P47 since the beginning."

P3 data • Immunology • Rheumatoid Arthritis

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. (PubMed, RMD Open) - "Efficacy equivalence, alongside comparable PK, safety and immunogenicity profiles, was determined between CT-P47 and r-TCZ in adults with RA, including after switching from r-TCZ to CT-P47."

Clinical • Journal • P3 data • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

A Study to Compare Efficacy and Safety of CT-P47 and RoActemra in Patients With Rheumatoid Arthritis (clinicaltrials.gov) - P3 | N=471 | Completed | Sponsor: Celltrion | Not yet recruiting ➔ Completed

Trial completion • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Pharmacokinetics and Safety of Intravenous Candidate Biosimilar CT-P47 and Reference Tocilizumab: A Randomized, Double-Blind, Phase 1 Study. (PubMed, J Clin Pharmacol) - "At the end of study, four (8.9%), one (2.3%), and two (4.5%) participants in the CT-P47, EU-tocilizumab, and US-tocilizumab groups, respectively, were ADA-positive; two (4.4%), zero (0%), and one (2.3%) in the respective groups were NAb-positive. CT-P47 demonstrated PK equivalence and comparable safety to EU- and US-tocilizumab."

Clinical • Journal • P1 data • PK/PD data

Pharmacokinetics and safety of candidate tocilizumab biosimilar CT-P47 administered by auto-injector or pre-filled syringe: a randomized, open‑label, single-dose phase I study. (PubMed, Expert Opin Biol Ther) - P1 | "PK equivalence between CT-P47 AI and CT-P47 PFS was demonstrated in healthy Asian adults, with comparable immunogenicity and safety between the two devices. ClinicalTrials.gov: NCT05617183."

Journal • P1 data • PK/PD data

PHARMACOKINETICS AND SAFETY OF CT-P47, A PROPOSED TOCILIZUMAB BIOSIMILAR, IN COMPARISON WITH INTRAVENOUS EU-APPROVED TOCILIZUMAB AND US-LICENSED TOCILIZUMAB; A PHASE 1, RANDOMIZED, DOUBLE-BLIND, THREE-ARM, SINGLE-DOSE STUDY IN HEALTHY JAPANESE SUBJECTS (EULAR 2024) - "CT-P47, EU-tocilizumab, and US-tocilizumab were bioequivalent as measured by primary PK endpoints and CT-P47 was determined to be safe and well tolerated in healthy subjects as compared with the comparators. Figure 1. Mean (± SD) Serum Concentrations of Intravenous Tocilizumab (PK Set) Abbreviations: EU-tocilizumab, European Union-approved tocilizumab; PK, pharmacokinetic; SD, standard deviation; US-tocilizumab, US-licensed tocilizumab."

Clinical • P1 data • PK/PD data • Inflammation

PHARMACOKINETICS, USABILITY AND SAFETY OF TOCILIZUMAB BIOSIMILAR (CT-P47) ADMINISTERED SUBCUTANEOUSLY BY AUTO-INJECTOR OR PRE-FILLED SYRINGE (EULAR 2024) - "PK similarity of CT-P47 AI and PFS was demonstrated in healthy subjects and high usability of CT-P47 AI was observed in RA patients. Also, CT-P47 AI was well tolerated and no new safety signal was found in both studies. These results suggest that the CT-P47 administered via AI could be an alternative option for tocilizumab treatment to patients, caregivers and healthcare professionals."

Clinical • PK/PD data • Gastrointestinal Disorder • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Arthritis • Leukopenia • Neutropenia • Oncology • Rheumatoid Arthritis • Rheumatology

SIMILAR EFFICACY, SAFETY, AND IMMUNOGENICITY OF TOCILIZUMAB BIOSIMILAR (CT-P47) AND REFERENCE TOCILIZUMAB IN PATIENTS WITH MODERATE-TO-SEVERE ACTIVE RHEUMATOID ARTHRITIS: WEEK 32 RESULTS FROM THE PHASE III SINGLE TRANSITION STUDY (EULAR 2024) - "The results demonstrated that CT-P47 was equivalent to ref-tocilizumab as measured by the DAS28 (ESR). Also, efficacy, PK, safety and immunogenicity profiles were comparable among groups after Week 24 up to Week 32. Thus, this study supports the biosimilarity of CT-P47 to ref-tocilizumab and clinical evidence for switching from ref-tocilizumab to CT-P47."

Clinical • P3 data • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Arthritis • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology

Celltrion showcases promising results in phase III study for CT-P47, a biosimilar candidate of RoActemra (tocilizumab) in patients with rheumatoid arthritis (RA) at EULAR 2024 (Businesswire) - P3 | N=448 | NCT05489224 | Sponsor: Celltrion | "Celltrion today presented positive Phase III data for CT-P47...at the...EULAR 2024. Data from the Phase III comparative clinical trial demonstrated that the investigational biosimilar candidate, CT-P47, has an equivalent efficacy, and comparable safety and immunogenicity profile to the reference tocilizumab product. The Phase III study randomised 471 patients with moderate to severe RA to receive either CT-P47 or reference tocilizumab every 4 weeks at a dose of 8 mg/kg for the first 20 weeks. The primary endpoint was disease activity score 28 (DAS28) erythrocyte segmentation rate (ESR), improvement at weeks 12 and 24. The estimated differences between the two groups were -0.01 at week 12 and -0.1 at week 24, and the confidence intervals of the difference were entirely within the pre-defined equivalence margins at both timepoints (95% CI: -0.26 to 0.24 at week 12 and 90% CI: -0.30 to 0.10 at week 24)."

P3 data • Rheumatoid Arthritis

Celltrion applies for Actemra biosimilar CT-P47’s sales license in Korea (Korea Biomedical Review) - "Celltrion said Thursday that it has completed submitting a marketing authorization application for CT-P47, a biosimilar to Actemra (tocilizumab) for treating autoimmune diseases, to the Ministry of Food and Drug Safety (MFDS)...Celltrion has applied for the marketing authorization of CT-P47 for the full-label indications of Actemra (European brand name: Roactemra) in Korea, such as rheumatoid arthritis (RA), giant cell arteritis (GCA), systemic juvenile idiopathic arthritis (sJIA), and polyarticular juvenile idiopathic arthritis (pJIA)....The filing is based on results from a global phase 3 clinical trial in 471 RA patients, which confirmed equivalence and similarity to the originator drug."

Non-US regulatory • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis

Celltrion seeks European approval for Actemra biosimilar (Korea Biomedical Review) - "Celltrion said it has completed its application for marketing authorization to the European Medicines Agency (EMA) for CT-P47, a biosimilar referencing Actemra....The drug generated global sales of approximately $2.8 billion in 2022, according to IQVIA, a drug market research firm. Celltrion decided to apply for approval based on the results from a global phase 3 clinical trial that demonstrated the biosimilar's equivalence and similarity to the original Actemra in treating rheumatoid arthritis, involving 471 patients."

European regulatory • Sales • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Celltrion USA completes submission of Biologics License Application for CT-P47, a biosimilar candidate of ACTEMRA (tocilizumab) (PRNewswire) - "Celltrion USA today announced the submission of Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for CT-P47, a biosimilar candidate of the reference product ACTEMRA (tocilizumab). The BLA submission was based on data from the global Phase III clinical trial designed to evaluate the efficacy, pharmacokinetics, safety, and immunogenicity of CT-P47 compared to the reference product ACTEMRA in patients with moderate to severe active rheumatoid arthritis with inadequate response to methotrexate up to Week 52....ACTEMRA is indicated for several indications, including moderate to severe rheumatoid arthritis in adults as well as juvenile idiopathic polyarthritis and systemic juvenile idiopathic arthritis....Celltrion is seeking approval for CT-P47 in both intravenous and subcutaneous routes of administration."

BLA • Inflammatory Arthritis • Rheumatoid Arthritis

Celltrion, Actemra similar 'CT-P47' Safety and effectiveness confirmed compared to the original [Google translation] (HIT News) - P3 | N=471 | NCT05489224 | Sponsor: Celltrion | "First, the company measured the change in DAS28 value compared to the baseline, which is a major indicator of RA activity, for the CT-P47 administration group and the original drug administration group as the primary evaluation index. As a result of the measurement, the difference between the original drug and the CT-P47 administration group met the predefined equivalence standards. Similar results were confirmed in the secondary evaluation index that evaluated the efficacy, pharmacokinetics, and safety of the three groups: CT-P47 administration group, original drug administration group, and replacement administration group with CT-P47 starting 24 weeks after original drug administration."

P3 data • Immunology • Rheumatoid Arthritis

BMS and 2seventy’s PDUFA for Abecma in Earlier-Line Multiple Myeloma Pushed to Accommodate New Adcomm Meeting (CGTLive) - "'The toxicity was actually similar in older patients and in younger patients,' Sergio Giralt, MD FACP, FASTCT...said in response to an audience question following his presentation. 'I do think it's important to recognize that there were there were 3% fatal events in the ide-cel arm versus 1% in the standard control. These were primarily sepsis. There was 1 case of severe fatal CRS that was associated with Candida sepsis and another case of CRS that also was fatal. I do think that there was a learning curve as we started doing this; particularly in patients with high tumor burden, we very rapidly decided that we needed to intervene early with steroids and tocilizumab at the first sign of CRS. Particularly one of the things we learned is if CRS occurs within the first 24 hours, those patients were at high risk of developing severe CRS, and we needed to intervene early.'"

Media quote

Celltrion unveils phase 1 clinical data of Actemra biosimilar in Europe (The Korea Economic Daily) - P1 | N=318 | "South Korean biosimilar giant Celltrion Inc. revealed on Wednesday the highly anticipated clinical phase 1 data for its Actemra biosimilar, CT-P47, at the 2023 European Congress of Rheumatology (2023 EULAR) conference....The clinical data for CT-P47 was made available online by Celltrion, following a phase 1 study involving 318 health South Korean subjects. The company announced that it had successfully demonstrated pharmacodynamic (PK) equivalence and safety comparable to the original drug."

P1 data • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Pharmacokinetics and safety of candidate tocilizumab biosimilar CT-P47 versus reference tocilizumab: a randomized, double-blind, single-dose phase I study. (PubMed, Expert Opin Investig Drugs) - P1 | "CT-P47 demonstrated PK equivalence with EU-tocilizumab and was well tolerated, following a single dose in healthy adults. www.clinicaltrials.gov identifier is NCT05188378."

Clinical • Journal • P1 data • PK/PD data

PHARMACOKINETICS AND SAFETY OF CT-P47, A PROPOSED TOCILIZUMAB BIOSIMILAR, IN COMPARISON WITH EU-APPROVED TOCILIZUMAB; A PHASE 1, RANDOMIZED, DOUBLE-BLIND, TWO-ARM, SINGLE-DOSE STUDY IN HEALTHY SUBJECTS (EULAR 2023) - "Conclusion This study demonstrated PK equivalence of CT-P47 to EU-approved tocilizumab in healthy subjects. Safety profiles, including immunogenicity, were comparable between groups."

Clinical • P1 data • PK/PD data • Pain