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Ordspono™ (odronextamab) approved in the European Union

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On August 26, 2024, Regeneron announced that the European Commission approved Ordspono™ (odronextamab) to treat adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) or R/R diffuse large B-cell lymphoma (DLBCL), after two or more lines of systemic therapy. This marks the first regulatory approval of Ordspono in the world for these patients.

Odronextamab (REGN1979) is a hinge-stabilized, bispecific human IgG4k antibody targeting CD20 and CD3 with an Fc that was modified to reduce Fc receptor binding. The antibody was derived from Regeneron’s VelocImmune® technology and Veloci-Bi® platform and is being developed for the treatment of RR B-cell NHL. In 2020, Regeneron granted Zai Lab rights to develop and exclusively commercialize odronextamab in oncology in mainland China, Hong Kong, Taiwan, and Macau. Odronextamab received Fast Track designation from FDA and Orphan Drug designations by the FDA and EMA for the treatment of patients with FL and DLBCL, which are subtypes of NHL.

The approval in the European Union is based on results from the Phase 1 ELM-1 (NCT02290951)  and pivotal Phase 2 ELM-2 (NCT03888105) trials, which demonstrated robust, durable response rates in adults with R/R FL or R/R DLBCL

  • Results from ELM-1 (N=60) in R/R DLBCL patients who had progressed after CAR-T therapy, as assessed by an independent review committee (IRC) showed 48% objective response rate (ORR), with 32% achieving a complete response (CR). Among responders (n=29), the median duration of response (DoR) was 15 months (95% CI: 3 months to not estimable (NE)).
  • Results from ELM-2 (N=127) in R/R DLBCL patients who were CAR-T therapy naive, as assessed by an IRC showed 52% ORR, with 31% achieving a CR. Among complete responders the median DoR was 18 months (95% CI: 10 months to NE).
  • In R/R FL, results from ELM-2 (N=128) as assessed by an IRC showed an objective response rate (ORR) of 80%, with 73% achieving a CR. Among complete responders, the median DoR was 25 months (95% confidence interval [CI]: 20 months to NE).

Regeneron submitted biologics license applications (BLAs) for odronextamab for RR FL and DLBCL to FDA. In March 2024, Regeneron announced that the FDA issued complete response letters for the Biologics License Applications for odronextamab. The company noted that FDA’s only approvability issue is related to the enrollment status of the confirmatory trials.

Call for papers – Deadline for inquiry submissions is April 1!

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The Antibody Society’s latest analysis of the current early-stage clinical pipeline of antibody therapeutics shows that the biopharmaceutical industry is engaging in innovative research and development. For both cancer and non-cancer indications, ~60% of the antibody therapeutics in early-stage clinical development target novel antigens, and a growing portion of those against well-validated targets have been designed in novel formats (e.g., bispecifics, bispecific biparatopics, antibody-drug conjugates (ADCs), Fc engineered, hybrid isotype, immunoconjugates).

For mAbs’ next Collection, we invite The Antibody Society members, mAbs readers, and the broader scientific community to contribute review articles focused on innovative approaches for antibody therapeutic discovery. The reviews should narrate the state of the art on innovative formats, targets, or platforms for antibody therapeutic discovery, and speculate on new vistas for the field.

mAbs will waive publication charges for up to 8 of the best review articles selected from pre-submission inquiries, which should include the proposed authors, title, abstract, and general outline of the intended review article.

The deadline for pre-submission inquiries is April 1, 2024.
Authors will be notified of the Editors’ decision by April 15, 2024.
The deadline for submission of the completed review articles is December 15, 2024.

We are particularly interested in reviews on the following topics:

  • Novel platforms for antibody therapeutic discovery (e.g., novel target/epitope selection, novel approaches for enhancing or reducing Fc effector function, novel methods for enhancing antibody therapeutics half-life).
  • Novel targets or formats for cancer immunotherapy (i.e., novel antigens and formats for targeting tumors, immune cells, and the tumor microenvironment), design strategies for novel approaches in cancer immunotherapy.
  • Novel targets or formats beyond oncology (e.g., autoimmune diseases, cardiovascular/hemostasis, neurology, infectious disease, ophthalmology, rare diseases).
  • Novel immune-modulating antibodies (i.e., novel immune checkpoints and immune agonists), relevant design strategies, formats, applications and considerations for safety and tolerability in multiple disease areas.
  • Innovative format combinations (e.g., Bispecific/Multispecific ADCs, Bispecific/Multispecific checkpoint inhibitors), design strategies for these molecules and considerations for safety.
  • Novel formats for well-validated targets, relevant design strategies and considerations for efficacy, biodistribution and safety.

Although these topics are especially of interest, we welcome well-written reviews in related areas as well.

Please send pre-submission inquiries that include the authors, title, abstract, and general outline of the intended review article to Editor-in-Chief Dr. Janice Reichert (reichert.biotechconsulting@gmail.com) and Guest Editors Drs. Silvia Crescioli (silvia.crescioli@antibodysociety.org) and Kristina Ilieva-Babinsky (k.m.ilieva@gmail.com), and Prof. Jamie Spangler (jamie.spangler@jhu.edu). Please feel free to contact us if you have any questions.

Examples of other mAbs Collections can be found here.

Crovalimab approved in China

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On February 8, 2024, Chugai Pharmaceutical Co., Ltd. announced that crovalimab (Chinese product name : 派圣凯®) was approved in the People’s Republic of China for treatment of adults and adolescents with paroxysmal nocturnal hemoglobinuria (PNH) not been previously treated with complement inhibitors. The regulatory application was filed by a China affiliate of F. Hoffmann-La Roche Ltd. because Roche is responsible for the development of crovalimab outside Japan and Taiwan. China is the first country in the world to approve crovalimab. Marketing applications for crovalimab have been submitted to regulatory agencies in the US, EU, and Japan.

Crovalimab (SKY59, RG6107, RO7112689) is a complement C5 inhibiting, humanized IgG1k antibody without effector functions that was engineered (M428L/N434A) to have enhanced affinity to FcRn at an acidic pH to extend its plasma half-life. Based on Chugai’s Recycling Antibody® technology, crovalimab is engineered to bind its antigen repeatedly, enabling sustained complement inhibition at a low dose administered subcutaneously (SC) every 4 weeks. Moreover, crovalimab binds a different epitope of C5 compared to existing antibody drugs, suggesting that it represents an alternative option for patients with PNH with a specific C5 gene mutation.

Crovalimab was granted Breakthrough Therapy for PNH by NMPA and the marketing application for crovalimab, which included data from the China-specific Phase 3 COMMODORE 3 study (NCT04654468), was accepted by NMPA under Priority Review.

COMMODORE 3 was a multicenter single-arm trial studying crovalimab in C5 inhibitor-naive patients with PNH in China. Patients (n=51) received crovalimab according to a weight-based dosing schedule, including loading (intravenous (IV) dose on Days 1 and 4, weekly SC doses starting from Day 2) and SC maintenance doses (every 4 weeks starting from Week 5); treatment continued after 24 weeks in patients with clinical benefit. The co-primary efficacy endpoints of hemolysis control and transfusion avoidance (TA) were met. The mean proportion of participants with hemolysis control from Week 5 through to Week 25 was 78.7% (95% CI: 67.8%, 86.6%).1 The difference between the proportion of participants with TA within 24 weeks prior to screening (0.0%) and the proportion of participants with TA from baseline through to Week 25 (51.0%) was statistically significant (p<0.0001). [1]

The global Phase 3 COMMODORE 1 (NCT04432584) and 2 (NCT04434092) studies assessed the efficacy and safety of crovalimab versus eculizumab in participants with PNH that are C5 inhibitor-experienced patients or not previously treated with complement inhibitors, respectively. COMMODORE 1 assessed safety, pharmacokinetics, pharmacodynamics, and exploratory efficacy of crovalimab. Data from the study support the favorable benefit–risk profile of crovalimab, including allowing for SC administration with the option to self-administer. [2] Data from the COMMODORE 2 study presented at European Hematology Association meeting in June 2023 in Frankfurt, Germany demonstrated that SC crovalimab Q4W was non-inferior in disease control to IV eculizumab Q2W with comparable safety for patients who have not been treated with C5 inhibitors. [3]

  1. Liu H, Xia L, Weng J, Zhang F, He C, Gao S, Jia J, Chang AC, Lundberg P, Camelia S. Sima CS, et al. Results from the first Phase 3 crovalimab (c5-inhibitor) study (commodore 3): efficacy and safety in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria (PNH). Presentation at: ASH Annual Meeting and Exposition; New Orleans, 2022 Dec 10-13; Abstract #293. doi.org/10.1182/blood-2022-162452.
  2. Scheinberg P, Cle D, Edwards J, Giai V, Hus M, Kim JS, Barrenetxea Lekue C, Nagy Z, Nur E, Panse J, et al. Phase III randomized, multicenter, open-label COMMODORE 1 trial: comparison of crovalimab vs eculizumab in complement inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria (PNH). Hemasphere. 2023; 7(Suppl ): e45540d8. 2023 Aug 8. doi: 10.1097/01.HS9.0000967644.45540.d8
  3. Röth A, He G, Brodsky A, Chai-Adisaksopha CC, Dumagay T, Demichelis R, Höglund M, Kelly R, Lee J-H, Nishimura J-I, et al. The PHASE III, randomized COMMODORE 2 trial: results from a multicenter study of crovalimab vs eculizumab in paroxysmal nocturnal hemoglobinuria (PNH) patients naive to complement inhibitors. Hemasphere. 2023; 7(Suppl ): e72750f1.

World Cancer Day 2024 – Antibody therapeutics for cancer indications

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For World Cancer Day 2024, The Antibody Society has prepared a snapshot of the clinical development of therapeutic antibodies for cancer indication.

The infographic gives an overview on the trends in first in human studies and approvals, as well as on the active early and late stage pipelines (as of January 2024).

“Antibodies to Watch in 2024” is now online!

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In this 15th installment of the annual ‘Antibodies to Watch’ article series, we review commercially sponsored monoclonal antibody therapeutics currently in late-stage clinical development, regulatory review, and those granted a first approval in any country in 2023. We also discuss clinical phase transition and overall approval success rates for antibody therapeutics, which are crucial to the biopharmaceutical industry because these rates inform decisions about resource allocation. Our analyses indicate that these molecules have approval success rates in the range of 14–32%, with higher rates associated with antibodies developed for non-cancer indications. Overall, our data suggest that antibody therapeutic development efforts by the biopharmaceutical industry are robust and increasingly successful.

Download or read the full paper here.

The complete abstract is here: The ‘Antibodies to Watch’ article series provides an annual summary of commercially sponsored monoclonal antibody therapeutics currently in late-stage clinical development, regulatory review, and those recently granted a first approval in any country. In this installment, we discuss key details for 16 antibody therapeutics granted a first approval in 2023, as of November 17 (lecanemab (Leqembi), rozanolixizumab (RYSTIGGO), pozelimab (VEOPOZ), mirikizumab (Omvoh), talquetamab (Talvey), elranatamab (Elrexfio), epcoritamab (EPKINLY), glofitamab (COLUMVI), retifanlimab (Zynyz), concizumab (Alhemo), lebrikizumab (EBGLYSS), tafolecimab (SINTBILO), narlumosbart (Jinlitai), zuberitamab (Enrexib), adebrelimab (Arelili), and divozilimab (Ivlizi)). We briefly review 26 product candidates for which marketing applications are under consideration in at least one country or region, and 23 investigational antibody therapeutics that are forecast to enter regulatory review by the end of 2024 based on company disclosures. These nearly 50 product candidates include numerous innovative bispecific antibodies, such as odronextamab, ivonescimab, linvoseltamab, zenocutuzumab, and erfonrilimab, and antibody–drug conjugates, such as trastuzumab botidotin, patritumab deruxtecan, datopotamab deruxtecan, and MRG002, as well as a mixture of two immunocytokines (bifikafusp alfa and onfekafusp alfa). We also discuss clinical phase transition and overall approval success rates for antibody therapeutics, which are crucial to the biopharmaceutical industry because these rates inform decisions about resource allocation. Our analyses indicate that these molecules have approval success rates in the range of 14–32%, with higher rates associated with antibodies developed for non-cancer indications. Overall, our data suggest that antibody therapeutic development efforts by the biopharmaceutical industry are robust and increasingly successful.