Published: September 2023
Owing to the broader clinical potential of bispecific antibodies in the treatment of variety of indications, this drug modality has garnered significant traction within the pharmaceutical industry. Our market report on Bispecific Antibody Therapeutics analyzes over 400 bispecific antibodies being developed by more than 155 drug developers for the treatment of wide range of disorders. In this article, discover details on 9 of the 13 approved bispecific antibodies and their respective developers.
A number of antibody therapeutics (more than 100) have been marketed for the treatment of patients suffering from various disease indications, primarily malignant tumors and other rare disorders. Despite the success, these drugs are associated with several limitations, such as increased patient resistance. Additionally, patent expiration of some of the blockbuster monoclonal antibodies have compelled the researchers and pharmaceutical companies to redesign these drugs and / or find new analogues. To further improve the specificity, efficacy and safety of monoclonal antibodies, the focus has gradually shifted towards the development of next generation recombinant antibodies, such as bispecific antibodies. Bispecific antibodies are a novel class of antibody therapeutics that act by simultaneously binding two separate and unique antigens (or different epitopes of the same antigen). The primary mechanism of action of these therapeutics involves redirection of immune effector cells for effective killing of cancer cells by antibody-dependent cell mediated cytotoxicity (ADCC) and other cytotoxic mechanisms, such as antibody dependent cellular phagocytosis (ADCP) and complement dependent cytotoxicity (CDC). Having unique biological and pharmacological properties, as well as their availability in different formats, bispecific antibodies have emerged as promising agents for therapeutic use. Advancements related to antibody and protein engineering techniques have led to the production of close to 50 new formats in the recent years.
The market approvals for bispecific antibodies have escalated since 2022. Till date, thirteen bispecific antibodies, namely Elrexfio™ (2023), Talvey™ (2023), Epkinly™ (2023), Columvi™ (2023), Cadonilimab (2022), Tecvayli™ (2022), Vabysmo™ (2022), Nanozora® (2022), Lunsumio™ (2022), Kimmtrak® (2022), Rybrevant® (2021), Hemlibra® (2017) and Blincyto® (2014) have been approved for therapeutic use demonstrating the growing popularity of bispecific antibodies. The escalating popularity and therapeutic potential of bispecific antibodies can also be correlated to an exponential increase in the number of clinical trials. In fact, multiple licensing agreements, between drug developers and technology providers, have also been inked in the past few years to advance the development of pipeline drug candidates. Roots Analysis has conducted an exhaustive study on Bispecific Antibodies Market featuring the current market landscape and future opportunity for the drug developers involved in the development of bispecific antibodies, over a span of 12 years.
The approved bispecific antibodies are listed below in detail (in order of approval from earliest to latest):
Interested in exploring all the 400+ Bispecific Antibodies?
This article highlights the 13 approved bispecific antibodies, which includes 9 FDA approved bispecific antibodies that have been developed by various pharmaceutical companies. Scroll below to read drug profiles for 9 bispecific antibodies that have received approval till December 2022.
Blincyto® (blinatumomab) is a scFv based BiTE antibody that was initially developed by Micromet (now acquired by Amgen) for the treatment of Ph (-) relapsed / refractory B-cell precursor ALL. It received accelerated FDA approval for the treatment of Ph (-) relapsed / refractory B-cell precursor ALL, Ph (+) relapsed / refractory B-cell precursor ALL and MRD (+) B-cell precursor ALL in March 2018. For FY 2022, the drug generated sales of USD 583 million, representing a 24% year-on-year growth.1 In H1 2023, Blincyto sales were USD 400 million.
Blincyto® is currently being used to target the following indications / patient segments:
| Indication / Patient Segment | Targeted Region |
| Philadelphia Chromosome-Negative Relapsed or Refractory B-cell Precursor Acute Lymphoblastic Leukemia | US, Canada, EU5, China, Japan and Australia |
| Philadelphia Chromosome-Positive Relapsed or Refractory B-cell Precursor Acute Lymphoblastic Leukemia | US and Japan |
| B-cell Precursor Acute Lymphoblastic Leukemia Minimal Residual Disease Greater Than or Equal to 0.1% | US and EU5 |
Recent Developments and Future Outlook
In June 2023, Amgen received the complete FDA approval for treatment of adults and pediatric patients suffering from CD19 positive B-cell precursor acute lymphoblastic leukemia, for which accelerated approval was given in March 2018.
Amgen mentioned that it will continue to advance its development pipeline for Blincyto®. This includes the studies that were aimed for the treatment of patients with MRD-negative B-ALL, studies that were designed to minimize the frequency of chemotherapy and studies designed for the investigation of subcutaneous formulation.
Hemlibra® (Emicizumab) is an asymmetric IgG4 bispecific monoclonal antibody developed by Roche and Chugai Pharmaceutical. The drug was discovered by Chugai Pharmaceutical using its proprietary ART-Ig platform. It received FDA approval for the treatment of hemophilia A with and without factor VIII inhibitors in November 2017, followed by EMA approval in January 2018. In the full year 2022, Hemlibra® generated sales of more than USD 4,326 million, showing year on year market growth of 27%. More than 60% of the revenues were generated from the US market, mainly driven by the co-pay assistance program in the country.2 In H1 2023, Hemlibra® generated revenues of USD 2,361 million.
Hemlibra® has significantly improved the quality of life of patients living with Hemophilia A, by offering once every four week subcutaneous administration.
Hemlibra® is currently being used to target the following indications / patient segments:
| Indication / Patient Segment | Targeted Region |
| Hemophilia A With Factor VIII Inhibitors | US, Canada, EU5 and Japan |
| Hemophilia A Without Factor VIII Inhibitors | US, Canada and EU5 |
Recent Developments and Future Outlook
In February 2023, Hemlibra® received label expansion in the EU as a routine prophylactic treatment for moderate Hemophilia A without inhibitors. Roche is also evaluating the safety and efficacy of Hemlibra® in infants with severe hemophilia A without inhibitors. The sales growth for the drug is expected to continue its upward trend as reimbursement is achieved in additional countries and label expansions are approved.
Rybrevant® (Amivantamab-vmjw) is a bispecific antibody that targets EGFR and MET receptors, which is being developed by Janssen Pharmaceutical. The drug binds extracellularly with the above-mentioned receptors in order to lead tumor growth inhibition. Rybrevant received FDA approval for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations in May 2021, followed by EMA approval in December 2021. The drug approval came with a companion diagnostic approval from Guardant Health. Guardant360 is a next generation sequencing based liquid biopsy test for identifying exon 20 insertion mutations.
Rybrevant® is currently being used to target the following indications / patient segments:
| Indication / Patient Segment | Targeted Region |
| Locally-advanced or Metastatic Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations | US, Canada, EU5, China, Japan and Australia |
Recent Developments and Future Outlook
In August 2023, Janssen Pharmaceuticals submitted sBLA for use of Rybrevant® in combination with chemotherapy for the treatment of patients suffering from newly diagnosed advanced / metastatic non-small cell lung cancer that shows EGFR exon 20 insertion mutations.
Janssen Pharmaceuticals is also evaluating the drug for NSCLC beyond exon 20 mutations in phase III clinical trials. Janssen is working on the label expansion for Rybrevant®, which is expected to be received in 2023 and 2024. These label expansions will contribute to the drug’s market growth.
Kimmtrak® (Tebentafusp-tebn) is a bispecific gp100 peptide-HLA-directed CD3 T cell engager, being developed by Immunocore. The drug is developed using the company’s proprietary ImmTAC technology platform, designed to redirect and activate T cells in order to elicit anti-tumor activity. In January 2022, it received FDA approval for the treatment of metastatic uveal melanoma. The FDA approval was followed by approval in the EU, Canada and Australia. In year 2022, the drug generated revenues of USD 141 million through sales in over more than 30 countries.3
Kimmtrak® is currently being used to target the following indications / patient segments:
| Indication / Patient Segment | Targeted Region |
| Unresectable or Metastatic Uveal Melanoma | US, Canada, EU5, China, Japan and Australia |
Recent Developments and Future Outlook
Post the approval for Kimmtrak®, Immunocore enter into a clinical trial agreement with Sanofi, in June 2022. The company mentioned that it intends to evaluate Sanofi’s SAR444245 in combination with Kimmtrak® for the treatment of patients suffering from metastatic cutaneous melanoma.
In H2 2022, Immunocore received various recognitions and awards for the clinical benefits demonstrated by Kimmtrak. Further, in November 2022, the company was awarded with SCRIP award in the UK and in December 2022, the company received prestigious Prix Galien France award for Kimmtrak. Further, it is worth highlighting that post the FDA approval, Kimmtrak also received approval from the European Commission and health authorities in the UK, Australia and Canada during the first half of 2022.
Vabysmo™ (Faricimab-svoa) is an anti VEGF-A / Ang-2 human IgG1- like bispecific antibody, being developed by Roche and Genentech, using the former company’s patented CrossMAb technology. It is worth highlighting that, in 2013, the molecule became the first bispecific antibody to be evaluated in a clinical trial in the field of ophthalmology.
In January 2022, it has received FDA approval for the treatment of diabetic macular edema and neovascular age related macular degeneration. The drug is also being evaluated in phase III studies for the treatment of macular edema secondary to branch retinal vein occlusion and macular edema secondary to central retinal vein occlusion. In 2022, the drug brought in USD 668 million in sales.2 In H1 2023, Vabysmo achieved blockbuster status with sales of more than USD 1082 million from its two approved indications in over 70 countries.
| Indication / Patient Segment | Targeted Region |
| Diabetic Macular Edema | US, Canada, EU5, China, Japan and Australia |
| Neovascular Age Related Macular Degeneration | US, Canada, EU5, China, Japan and Australia |
| Macular Edema Secondary to Branch Retinal Vein Occlusion | US, Canada, EU5, China, Japan and Australia |
| Macular Edema Secondary to Central Retinal Vein Occlusion | US, Canada, EU5, China, Japan and Australia |
Recent Developments and Future Outlook
In May 2023, Roche announced that it has successfully completed the negotiations with pan-Canadian Pharmaceutical Alliance for access of Vabysmo™ to all the Canadians. The company mentioned that Vabysmo™ is now available in Canada for the treatment of neovascular (wet) age-related macular degeneration and diabetic macular edema.
Roche mentioned that, as the next step, it is committed to work with other provincial jurisdictions in order to make Vabysmo™ available in other geographies as well.
Further, in May 2023, the FDA accepted the biologics license application for Vabsymo for treatment of macular edema following retinal vein occlusion, which will be the third indication for the drug when approved.
Cadonilimab, Helping the Patients Suffering From Relapsed / Metastatic Cervical Cancer
Cadonilimab (AK104) is one of the recombinant humanized IgG1 bispecific antibodies, which is being developed by China based Akeso Biopharma. In June 2022, Akeso Bio achieved a milestone with the NMPA approval for the world’s first dual immune checkpoint inhibitor, Kaitanni (cadonilimab / AK104). The drug binds to programmed cell death protein 1 (PD-1) and cytotoxic T- lymphocyte-associated antigen protein 4 (CTLA-4), simultaneously, in order to elicit anti-tumor activity. It has received marketing approval for the treatment of relapsed or metastatic cervical cancer, in China. Currently, the drug is being evaluated in phase III trials for the treatment of 1-L locally advanced cervical cancer, 1-L locally advanced unresectable or metastatic gastric cancer and locoregionally-advanced nasopharyngeal carcinoma.
Cadonilimab (AK104) is currently being used to target the following indications / patient segments:
| Indication / Patient Segment | Targeted Region |
| Relapsed or Metastatic Cervical Cancer | US, Canada, EU5, China, Japan, and Australia |
| 1-L Locally Advanced Cervical Cancer | US and Canada |
| 1-L Locally Advanced Unresectable or Metastatic Gastric Cancer | US, Canada, China, and Japan |
| Locoregionally-advanced Nasopharyngeal Carcinoma | US, Canada, China, and Japan |
Recent Developments and Future Outlook
In March 2022, Akeso Bio entered into a clinical trial agreement with Chipscreen Biosciences. The purpose of the agreement was to evaluate Cadonilimab in combination with Chiauranib for the treatment of patients suffering from ES-SCLC which progressed post the treatment with platinum-based chemotherapy and PD-(L)1 inhibitor as the first line treatment.
In March 2023, the company announced the completion of patient enrollment for its phase III clinical trial for Cadonilimab. The company also mentioned that post the approval of Cadonilimab for cervical cancer, this achievement marks a step closer for the approval of Cadonilimab for the treatment of patients suffering from advanced gastric cancer.
Recently, in June 2023, Akeso Bio, presented positive results from a phase Ib/II clinical study of Cadonilimab at 2023 American Society of Clinical Oncology Annual Meeting.
Akeso Bio is looking forward to introduce new therapeutic solutions for the treatment of patients suffering from cancers, such as lung cancer.
Lunsumio™ (Mosunetuzumab) is one of the anti-CD20 x CD3 T-cell engaging bispecific antibodies, which is being developed by Roche. The drug binds to the target antigens, in order to redirect T-cell cytotoxic activity to cancer cells. In November 2021, the drug was designated an orphan medicine status by the European medicine agency for the treatment of follicular lymphoma. The EMA provided conditional approval to the drug in June 2022. Further, it received FDA approval for the treatment of follicular lymphoma in December 2022. The drug is currently being evaluated in phase III trial for the treatment of relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma and follicular lymphoma after at least one line of systemic therapy.
Lunsumio™ is currently being used to target the following indications / patient segments:
| Indication / Patient Segment | Targeted Region |
| 2L+ Relapsed or Refractory Follicular Lymphoma | US, Canada, EU5, China, Japan and Australia |
| 1-L+ Relapsed or Refractory Follicular Lymphoma | US, Canada and EU5 |
| Relapsed or Refractory Aggressive B-Cell Non-Hodgkin's Lymphoma | US, Canada, China and Japan |
| Systemic Lupus Erythematosus | US and EU5 |
Recent Developments and Future Outlook
The approval of Lunsumio™ has also proved to be a positive news for Biogen, which had exercised its option for co-development of the drug in February 2022. The company had paid an upfront option fee of USD 30 million to Genentech in return for sharing operating profits in the US and royalties on sales outside the US, subject to certain conditions.
Roche has been developing bispecific antibodies for non-oncological indications as well. As such, Lunsumio™ is also being evaluated for the treatment of Systemic Lupus Erythematosus in phase I clinical trial. This is an immunological disorder, unlike its evaluation for oncological indications in all the other clinical trials.
Tecvayli™ (Teclistamab) is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, which is being developed by Janssen Pharmaceutical. The drug is based on Genmab’s technology platform, DuoBody. The bispecific antibody first received EMA approval for the treatment of relapsed or refractory multiple myeloma in August 2022, followed by FDA approval in October 2022. This was the first bispecific antibody to receive approval for treatment of multiple myeloma. In August 2023, Tecvayli received competition after FDA approved Pfizer’s Elrexfio (Elranatamab) for the indication. Pfizer has launched Elrexfio with a more convenient dosing schedule which includes subcutaneous administration every other week after 24 weeks of weekly treatment, unlike weekly subcutaneous administration for Tecvayli.
Janssen also expanded its multiple myeloma portfolio with the approval of Talvey (Talquetamab-tgvs), another bispecific antibody in August 2023. Talquetamab mechanism of action differs from teclistamab by targeting GPRC5D and CD3.
Tecvayli™ is currently being used to target the following indications / patient segments:
| Indication / Patient Segment | Targeted Region |
| Relapsed or Refractory Multiple Myeloma | US, Canada, EU5, China, Japan and Australia |
Recent Developments and Future Outlook
In August 2023, Janssen announced EMA approval for a reduced dosage frequency of Tecvayli™ for the approved indication. The drug is currently administered once a week, with patients required to visit the hospital for administration. However, EMA approved once every two weeks administration in a specific set of patients. Although competing with CAR-T cell therapies for the indication, Tecvayli™ provides the benefit of off-the-shelf availability for relapsed / refractory patients who have limited treatment options left.
Janssen has strong presence in the multiple myeloma market with its portfolio including two bispecific antibodies, a CAR-T Carvykti and a monoclonal antibody Darzalex.
Nanozora® (Ozoralizumab) is a TNF-α x HAS targeting bispecific antibody which is being developed by Taisho Pharmaceutical and Ablynx (a part of Sanofi). This drug was derived using Nanobody technology. It received marketing approval for the treatment of rheumatoid arthritis, in Japan in September 2022. The subcutaneously administered bispecific nanobody was launched in Japan in December 2022 after its inclusion in the NHI drug price list.
Nanozora® is currently being used to target the following indications / patient segments:
| Indication / Patient Segment | Targeted Region |
| Rheumatoid Arthritis | US, Canada, EU5, China, Japan and Australia |
Recent Developments and Future Outlook
In July 2023, Taisho Pharmaceuticals received approval for Autoinjector dosage form of Nanozora®, which is in addition to the originally launched 30 ml syringe dosage form. The disposable autoinjector will provide user friendly option for the patients with RA. Once launched the autoinjector will allow self-administration and help in improved acceptance amongst the patients.
The above presentation features 9 approved bispecific antibodies from 13 marketed products. These are from a pool of over 400 bispecific antibodies for which we have compiled information. If you're interested, you can download the Sample Report on this topic by Roots Analysis. For personalized assistance in identifying the most relevant solutions based on your specific criteria, please don't hesitate to reach out to us at sales@rootsanalysis.com.
Ankita_Kashyap is an associate, working with Roots Analysis since 2019. She has a master’s in pharmacology from a renowned university. Post completing her degree, she embarked upon her career with us. She started her journey as a business analyst with Roots Analyst and in such a short span of time, she has demonstrated amazing dedication. Till date, she has contributed to over 20 research reports.
Source 1: https://www.amgen.com/newsroom/press-releases/2023/01/amgen-reports-fourth-quarter-and-full-year-2022-financial-results
Source 2: https://assets.cwp.roche.com/f/126832/x/8971737b76/fb22e.pdf
Source 3: https://ir.immunocore.com/news-releases/news-release-details/immunocore-reports-2022-financial-results-and-provides-business
MEDIA CITATIONS
We are your partners with no equity
We fit in your budget
We love what we do
Chance to prove ourselves
Best in class quality of work
Most trusted consulting partner in the industry
SUBSCRIBE TO INDUSTRY UPDATES
.png)
