In “Antibodies to Watch in 2022”, Drs. Janice Reichert, Alicia Chenoweth and Silvia Crescioli will discuss key events in antibody therapeutics development that occurred in 2021 and forecast events that might occur in 2022. The COVID-19 pandemic continued to pose challenges and opportunities to the healthcare system, but companies forged ahead with development plans, resulting in record numbers of antibody therapeutics in late-stage clinical studies and in regulatory review. Globally, regulatory agencies approved a record number of novel antibody-based products, including anti-SARS-CoV-2 antibodies. The speakers will provide details of 2021 events and trends in the development of antibody therapeutics projected for 2022.
On November 11, 2021, the European Medicines Agency’s human medicines committee recommended authorizing anti-SARS-CoV-2 antibody therapeutics Ronapreve (casirivimab/imdevimab) and Regkirona (regdanvimab) for COVID-19.
- The Committee recommended authorizing Ronapreve for treating COVID-19 in adults and adolescents (from 12 years of age and weighing at least 40 kilograms) who do not require supplemental oxygen and who are at increased risk of their disease becoming severe. Ronapreve can also be used for preventing COVID-19 in people aged 12 years and older weighing at least 40 kilograms. The company that applied for authorization of Ronapreve was Roche Registration GmbH.
- The Committee recommended authorizing Regkirona for treating adults with COVID-19 who do not require supplemental oxygen and who are also at increased risk of their disease becoming severe. The applicant for Regkirona was Celltrion Healthcare Hungary Kft.
On August 20, 2021, the European Commission authorized marketing of Bimzelx (bimekizumab) in the EU for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy. Bimekizumab is a humanized IgG1 kappa antibody that selectively inhibits IL-17A and IL-17F by binding regions that are common to these pro-inflammatory cytokines, which share ~50% sequence identity and are expressed as homodimers and IL-17A/F heterodimers. Bimekizumab is approved at a recommended dose of 320 mg, administered by two subcutaneous injections every four weeks to week 16 and every eight weeks thereafter. 
The decision to grant a marketing approval was supported by results from 3 Phase 3 studies that included an active comparator arm, ustekinumab (Stellara®; BE VIVID study; NCT03370133), adalimumab (Humira®; BE SURE study; NCT03412747), or secukinumab (Cosentyx®; BE RADIANT study; NCT03536884). All three pivotal studies met their co-primary endpoints at Week 16, demonstrating superiority of bimekizumab over the active comparator in certain defined measures (e.g., Psoriasis Area and Severity Index). Clinical responses achieved with bimekizumab at Week 16 were maintained up to one year. [2-4] Coprimary endpoints were also met in the Phase 3 BE READY study (NCT03410992), which investigated the efficacy and safety of bimekizumab in patients with moderate to severe plaque psoriasis compared to placebo. 
Bimzelx is the 8th antibody therapeutic to be first approved for marketing in the EU or US in 2021.
- European Medicines Agency. Bimzelx public assessment report.
- Reich K, Papp KA, Blauvelt A, et al. Bimekizumab versus ustekinumab for the treatment of moderate to severe plaque psoriasis (BE VIVID): efficacy and safety from a 52-week, multicentre, double-blind, active comparator and placebo-controlled phase 3 trial. Lancet. 2021;397(10273):487-498.
- Warren RB, Blauvelt A, Bagel J, et al. Bimekizumab versus Adalimumab in Plaque Psoriasis. N Engl J Med. 2021;385(2):130-141.
- Reich K, Warren RB, Lebwohl M, Gooderham M, Strober B, Langley RG, Paul C, De Cuyper D, Vanvoorden V, Madden C, Cioffi C, Peterson L, Blauvelt A. Bimekizumab versus Secukinumab in Plaque Psoriasis. N Engl J Med. 2021 Jul 8;385(2):142-152.
- Gordon KB, Foley P, Krueger JG, et al. Bimekizumab efficacy and safety in moderate to severe plaque psoriasis (BE READY): a multicentre, double-blind, placebo-controlled, randomised withdrawal phase 3 trial. Lancet. 2021;397(10273):475-486.
The extraordinary scale of the COVID-19 pandemic has elicited extraordinary responses world-wide, but the resulting disruptions have raised concerns about delays in approval of non-COVID-19 antibody therapeutics.
As part of the virtual Antibody Engineering & Therapeutics Europe conference, Dr. Janice Reichert, Executive Director of The Antibody Society, provided an update on non-COVID-19 antibody therapeutics approved so far in 2020, and those that might be approved by the end of the year. She also discussed the biologics currently in development for COVID-19, which includes over 50 repurposed biologics and over 80 anti-SARS-CoV-2 biologics.
Broadcast date: Thursday August 27, 2020.
Updated presentation slides can be downloaded here.
Dataset of commercially sponsored biologic COVID-19 interventions can be downloaded here.
As regulatory agencies tasked with evaluating and monitoring the development of medicines, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have pivotal roles in the global response to the COVID-19 pandemic. However, these critical activities have been added to an already substantial workload. FDA and EMA are continuing the ongoing marketing application reviews for drugs that are not COVID-19 interventions, and they will need to process new applications submitted throughout 2020. FDA and EMA’s distribution of work is particularly relevant to new antibody therapeutics because a substantial number of license applications for these drugs, none of which relate to COVID-19, are undergoing FDA or EMA review. In a recent statement, FDA offered assurances that their application review teams are focused on their work, but noted that they may not be able to sustain the current level of performance indefinitely.
In total, biologics license applications (BLAs) for 14 new antibody therapeutics (i.e., not previously approved by any agency for any indication) are undergoing FDA review. EMA is reviewing marketing authorization applications (MAAs) for 4 of these 14 antibody therapeutics, and MAAs for 4 antibody therapeutics that are already approved in the US.
New antibody therapeutics undergoing FDA review
The 14 antibody therapeutics undergoing FDA review are treatments for a variety of diseases, including numerous cancers, neuromyelitis optica spectrum disorders, osteoarthritis pain, diabetes, thrombotic microangiopathies, Ebola and HIV infection. The drugs for cancer are:
- Sacituzumab govitecan, anti-TROP-2 humanized IgG1 antibody-drug conjugate for triple-neg. breast cancer
- Belantamab mafodotin, anti-B-cell maturation antigen humanized IgG1 antibody-drug conjugate for multiple myeloma
- Tafasitamab, anti-CD19 humanized IgG1 for diffuse large B-cell lymphoma
- Naxitamab, anti-GD2 humanized IgG1 for high-risk neuroblastoma and refractory osteomedullary disease
- Oportuzumab monatox, anti-EpCAM humanized scFv immunotoxin for bladder cancer
- Margetuximab, anti-HER2 chimeric IgG1 for HER2-positive metastatic breast cancer
- Dostarlimab, anti-PD-1 humanized IgG4 for endometrial cancer
The drugs for non-cancer indications are:
- Inebilizumab, anti-CD19 humanized IgG1 for neuromyelitis optica and neuromyelitis optica spectrum disorders
- Satralizumab, anti-IL-6R humanized IgG2 for neuromyelitis optica spectrum disorders
- Tanezumab, anti-nerve growth factor humanized IgG2 for pain due to osteoarthritis of the knee or hip
- Teplizumab, anti-CD3 humanized IgG1 for type 1 diabetes
- Narsoplimab, anti-MASP-2 human IgG4 for hematopoietic stem cell transplant-associated thrombotic microangiopathies
- Leronlimab, anti-CCR5 humanized IgG4 for HIV infection
- REGNEB3, a mixture of 3 human IgG1 targeting the Ebola virus for Ebola disease.
A first review cycle for the BLAs for all 14 should be completed by the end of 2020. Despite the pandemic, 2020 may be a record year for new antibody therapeutics approvals (potentially 17, including the 14 discussed here and the approvals for teprotumumab-trbw (Tepezza®), eptinezumab-jjmr (Vyepti®) and isatuximab-irfc (Sarclisa®) already granted in 2020, or more).
Antibody therapeutics undergoing EMA review
Like FDA, EMA is continuing to process MAAs for antibody therapeutics despite the increase in workload due to COVID-19. EMA provides monthly updates on applications for centralized marketing authorization for human medicines that they have received for evaluation. EMA’s information as of April 6, 2020, indicates that they are evaluating MAAs for 8 antibody therapeutics that, if approved, would be new to the European Union. These 8 are Belantamab mafodotin, Dostarlimab, Satralizumab and Tanezumab, which are also being reviewed by FDA, as well as:
- Obiltoxaximab (Anthim®), anti-B. anthrasis protective antigen chimeric IgG1 approved by FDA for prevention of inhalational anthrax in 2016
- Emapalumab (Gamifant®), anti-IFN gamma human IgG1 approved by FDA for primary hemophagocytic lymphohistiocytosis in 2018
- Moxetumomab pasudotox (Lumoxiti®), anti-CD22 murine IgG1 dsFv immunotoxin approved by FDA for hairy cell leukemia in 2018
- Crizanlizumab (Adakveo®) anti-P-selectin humanized IgG2 approved by FDA for sickle cell disease in 2019
Other antibodies to watch in 2020
The COVID-19 pandemic might delay the submission of marketing applications for antibody therapeutics that are now in late-stage clinical studies. As documented by Kaplon et al. in ‘Antibodies to watch in 2020’, companies developing 5 antibody therapeutics for cancer (spartalizumab, 131I-omburtamab, loncastuximab tesirine, balstilimab, and zalifrelimab) and 5 for non-cancer indications (aducanumab, evinacumab, etrolizumab, sutimlimab, and anifrolumab) had previously announced plans to submit applications to regulatory agencies during 2020. The Antibody Society will continue to monitor the development of these product candidates and report on progress. Discussion of these antibodies can be found in the ‘Antibodies to watch in 2020’ paper.