The most noteworthy new antibody drugs of 2021

At The end of each year, starting in 2010, The Antibody Society publishes a report that summarizes The progress of new drugs in The field of antibodies. This is the agency's 12th report. According to the report, 16 antibody drugs, including antibody conjugates, are under regulatory review in the United States or the European Union, with a chance of receiving the world's first regulatory approval in 2021. However, two drugs in the report were approved by the US FDA in late December 2020, respectively:

Margenza (Margetuximab-cmkb) : Margetuximab-cmkb, developed by Zai Pharmaceutical Partners MacroGenics, is a HER2-targeted therapy approved by the FDA in combination with chemotherapy for adult patients with metastatic HER2-positive breast cancer who have received at least two anti-HER2 regimens, of which at least one is used for the treatment of metastatic disease. This drug is a novel Fc domain optimized immunoenhanced mAb developed using MacroGenics proprietary Fc optimization technology platform. It has HER2 binding and anti-proliferation effects similar to trastuzumab, and its engineered Fc domain can enhance the participation of the immune system. Notably, Margenza is the first HER2-targeted therapy to significantly improve progression-free survival (PFS) compared to trastuzumab in a head-to-head phase 3 clinical trial.

-- Ebanga (Ansuvimab-Zykl, MAB114) : Ebanga (Ansuvimab-Zykl, MAB114), a monoclonal antibody developed by Ridgeback Biotherapeutics, has been approved by the FDA for use in adult and pediatric patients, including newborn babies born to mothers who test positive for the Zaire Ebola virus (Zaire ebolavirus), for the treatment of infections caused by the Zaire Ebola virus. Ebanga is the second Ebola drug to be approved by the FDA, following Inmazeb, a cocktail of regenerative antibodies. Ebanga blocks the binding of the Ebola virus to a cell receptor, preventing the virus from entering cells.

The following is a review of the remaining 14 antibody drugs in the report, updated and supplemented according to the information on each company's website. Among them, the first 10 antibody drugs (tanezumab, narsoplimab, evinacumab, aducanumab, tralokinumab, teplizumab, inolimomab, bimekizumab, anifrolumab, sutimlimab) are used for non-cancer indications. The latter four antibody drugs (oportuzumab monatox, dostarlimab, balstilimab, loncastuximab tesirine) were used for cancer indications.

1, tanezumab

Tanezumab is a humanized IgG2K monoclonal antibody that works by selectively targeting the blocking of nerve growth factor (TNF). Tanezumab is being evaluated for the treatment of osteoarthritis (OA) pain and chronic low back pain (CLBP). Levels of NGF are elevated when the body is in a state of injury, inflammation, or chronic pain. By selectively blocking NGF, tanezumab may help prevent pain signals produced by muscles, skin or organs from reaching the spinal cord and brain. Tanezumab has a novel mechanism of action that is different from opioids and other pain relievers, including non-steroidal anti-inflammatory drugs [NSAIDs]. In studies to date, tanezumab has not been shown to be at risk for addiction, misuse, or dependence.

Tanezumab is made by Pfizer Inc., with which Lilly signed a $1.8 billion deal in 2013 to co-develop and commercialize the drug globally. In June 2017, the US FDA granted Tanezumab fast track status for the treatment of OA pain and CLBP. Notably, Tanezumab is the first NGF inhibitor to be fast-tracked and has the potential to be the first first-in-class drug of its kind for the treatment of OA pain and CLBP.

Currently, Tanezumab's biologic license application (BLA) for the treatment of OA pain is under review by the FDA, with a December 2020 target date under the Prescription Drug User Fee Act (PDUFA). But tanezumab has not yet been approved, according to the FDA's new drug database and the Pfizer/Eli Lilly website. It is also under review by the European Medicines Agency (EMA).

2, narsoplimab

Narsoplimab is a full-body IgG4λ antibody targeting mannose-binding lectin associated serine proteinase 2 (MASP-2) for the treatment of thrombotic microangiopathy (HSCT-TMA) associated with hematopoietic stem cell transplantation. Narsoplimab is a full-body IgG4λ antibody targeting mannose-binding lectin associated serine proteinase 2 (MASP-2) for the treatment of thrombotic microangiopathy (HSCT-TMA) associated with hematopoietic stem cell transplantation.

Narsoplimab, developed by Omeros, is licensed as a breakthrough drug for the treatment of high-risk patients with HSCT-TMA in the United States, for the prevention of complement-mediated thrombotic microangiopathy (TMA) and for the treatment of HSCT-TMA in the European Union, and for the treatment of hematopoietic stem cell transplantation (HSCT) in the European Union. Omeros initiated rolling BLAs for narsoplimab in patients at high risk for HSCT-TMA to the U.S. FDA in October 2019 and completed those submissions in November 2020. The BLA is currently under review by the US FDA. The company also plans to submit a marketing authorization application (MAA) for narsoplimab for the treatment of HSCT-TMA to the EMA.

3, evinacumab

Evinacumab is a full-body IgG4K antibody that targets to bind to and block the function of angiopoietin like protein 3 (AngPTL3). AngPTL3 regulates lipid metabolism, including low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides.

Evinacumab was developed from regenerative cells for the treatment of homozygous familial hypercholesterolemia (HOFH). In 2017, the FDA granted evinacumab breakthrough drug status for the treatment of hypercholesterolemia in patients with HOFH. Notably, the drug is the first of its kind to show efficacy in treating patients with HOFH, including those with little or no LDL receptor function. Evinacumab's BLA for HOFH is currently under FDA review, with a PDUFA target action date of February 11, 2021. In the European Union, the EMA awarded evinacumab for accelerated evaluation in June 2020.

4, aducanumab

Aducanumab is an IgG1K antibody that targets amyloid beta (Aβ) for the treatment of Alzheimer's disease (AD). The drug was licensed by Bo Jian from Neurimmune Holding AG in 2007 and has been developed and commercialized globally in cooperation with Eisai since 2017. Currently, aducanumab is under FDA priority review with a PDUFA target date of March 7, 2021. In addition, aducanumab is also under review by the European Union's EMA. The FDA had previously granted aducanumab fast track status. The EMA has also included the drug in its Priority Medicines (PRIME) programme.

Aducanumab is the first biologic agent to be submitted to regulatory authorities to target the decline and pathologic mechanisms of AD-related clinical symptoms. In clinical trials, aducanumab has been shown to remove Aβ from the brain and slow the clinical decline of AD and mild cognitive impairment (MCI) due to mild AD dementia. The drug is a highly anticipated and controversial one. If approved, the drug would be the first treatment to meaningfully alter the progression of AD and slow its clinical decline, as well as the first to demonstrate that removal of amyloid beta can lead to better clinical outcomes.

5, tralokinumab

Tralokinumab is a global IgG4λ antibody that targets interleukin 13 (IL-13) and is being developed for the treatment of a variety of inflammatory diseases, including atopic dermatitis. IL-13 is an important cytokine that plays a key role in driving the underlying inflammation of atopic dermatitis. By specifically binding IL-13 with a high affinity, tralokinumab blocks the interaction of IL-13 with its receptor and subsequent downstream IL-13 signaling.

Tralokinumab is being developed by Leo Pharma, which acquired it from AstraZeneca in July 2016. Tralokinumab's BLA for moderate to severe atopic dermatitis is currently under FDA review, with a PDUFA target date of 2Q2021. In addition, the European EMA accepted the MAA for tralokinumab in June 2020. If approved, tralokinumab will be the first biologic agent to challenge Sanofi/Dupixent, which is currently the leading product and only biologic agent in the treatment of atopic dermatitis (AD). Tralokinumab was approved in China in June 2020.

6, teplizumab

Teplizumab is a humanized IgG1K antibody that targets the CD3ε epitome expressed on mature T lymphocytes to modulate the pathological immune response inherent in type 1 diabetes mellitus (T1D) and other autoimmune diseases. Teplizumab has been awarded Breakthrough Drug designation by the U.S. Food and Drug Administration (FDA) and Priority Drug designation by the European Union's European Medicines Agency (EMA) for the prevention or delay of clinical T1D in people at high risk of developing T1D, defined as the presence of two or more T1D-related autoantibodies.

Teplizumab was developed by ProVention Bio, which was acquired from MacroGenics in 2018. In the United States, ProVention Bio started rolling BLA submission to the FDA in April 2020 and completed it in November 2020, and the company has asked the FDA for priority review. If approved, teplizumab would be the first treatment to prevent/delay progression to clinical T1D in high-risk individuals.

7, inolimomab

Inolimomab(leukoTAC) is a mouse IgG1K monoclonal antibody that targets interleukin-2 (IL-2) receptors. IL-2 is a cytokine that contributes to the development and proliferation of certain white blood cells, including T cells associated with acute graft-versus-host disease (AGVHD). By specifically binding to the alpha chain of this receptor (CD25), inolimomab blocks the surface of IL-2 and the proliferation of donor overactive T cells.

Inolimomab, developed by Elsaly Biotech, a division of Mediolanum Farmaceutici SpA, is currently under review under the U.S. Food and Drug Administration's Real-Time Oncology Review Pilot Program (0RTOR) for the treatment of adult patients with grade II-IV steroid-refractory acute graft-versus-host disease (SR-AGVHD). The role of inolimomab in SR-AGVHD is mainly due to its specific and preferred affinity for CD25 receptors on the surface of T lymphocytes.

8 bimekizumab.

Bimekizumab is a humanized IgG1K antibody that has a dual mechanism of action. It effectively and selectively neutralizes IL-17A and IL-17F, two key cytokines that drive the inflammatory process. IL-17A and IL-17F have similar pro-inflammatory functions and work independently with other inflammatory mediators to drive chronic inflammation and damage in multiple tissues. Bimekizumab's unique IL-17A/IL-17F dual neutralization has the potential to provide a novel targeted therapy for immune-mediated inflammatory diseases.

Bimekizumab is being evaluated for the treatment of a variety of inflammatory diseases, including plaque psoriasis, psoriatic arthritis, ankylost spondylitis, and non-radiological axial arthritis of the spine. Currently, the BLA and MAA of the drug for the treatment of moderate to severe plaque psoriasis in adults are under review by the US FDA and the EU EMA.

9 anifrolumab.

Anifrolumab (Medi-546) is a full-body IgG1K antibody that specifically binds type I interferon receptor subunit 1 and blocks the activity of all type I interferons, including IFNα, IFNβ and IFN-ω-cytokines, which are involved in inflammatory pathways. Three mutations (L234F, L235E, and P331S) were incorporated into the heavy chain of anifrolumab to reduce effector function. The drug was developed to treat systemic lupus erythematosus (SLE), a debilitating autoimmune disease, but only one new treatment has been approved in the past 60 years, GlaxoSmithKline's Benlysta (Bilientum, Belicuximab). In China, Benlysta was approved in July 2019 and is the world's first biologic for the treatment of SLE.

Anifrolumab, developed by AstraZeneca, is being reviewed by the US FDA and EU EMA for BLA and MAA for the treatment of adults with moderate to severe activity and positive autoantibodies for SLE, with approval expected in the second half of 2021. Anifrolumab was previously granted fast track status by the FDA for the treatment of SLE. It is estimated that 60-80% of adults with SLE have an elevated type I interferon gene signature, which has been shown to be associated with disease activity. Clinical data demonstrated that anifrolumab reduces disease activity in patients with SLE by targeting type I interferon receptors. If approved, anifrolumab could bring a new treatment option to the population of patients with SLE.

10, sutimlimab

Sutimlimab is a humanized IgG4 antibody developed for the treatment of primary cold agglutinin disease (CAD) hemolysis. Sutimlimab selectively targets and inhibs the serine protease C1s in the C1 complex of the complement system, the first step in the activation of the classical complement pathway of the immune system.

Sutimlimab, developed by Sanofi, is receiving priority review by the U.S. Food and Drug Administration (FDA) for the treatment of hemolysis in adults with CAD. Sutimlimab has previously been granted Breakthrough Drug and Orphan Drug status by the FDA, as well as Orphan Drug status by the European Union's EMA.

11, oportuzumab monatox

Oportuzumab monatox is A local drug delivery for the next generation of antibody coupling drugs (ADC), is the tumor cell surface antigen of epithelial cell adhesion molecule (EpCAM) for the targets of humanized scFv immune toxin, by recombinant humanized EpCAM antibodies scFv and resistance pseudomonas exotoxin A coupling and become, once combined with cancer cells express EpCAM will be internalized into the cytoplasm, inducing cell apoptosis.

The drug was developed by Sesen Bio for the treatment of high-risk, non-muscular-invasive bladder cancer (NMIBC) that does not respond to BCG. Preclinical studies have confirmed that EpCAM is overexpressed in NMIBC cells and almost not expressed in normal bladder cells. In the United States and the European Union, Oportuzumab monatox was granted orphan drug status in 2005 and fast track status by the FDA in August 2018 for the treatment of NMIBC, which is resistant to BCG immunotherapy. In December 2019, Sesen Bio initiated rolling BLA submissions to the FDA, which will be completed in December 2020, and the company has asked the FDA for priority review of the BLA.It is worth noting that on November 14, 2020, the FDA issued a full response letter (CRL) to Sutimlimab's BLA, noting that certain deficiencies were identified during preapproval inspections (PLI) of third-party facilities responsible for manufacturing. Before the BLA can be approved, the deficiencies mentioned in the CRL need to be satisfactorily resolved by the third party manufacturer. Sanofi is working to address these issues. A timely resubmission of the BLA will allow Sutimlimab to still have a chance for approval in 2021. If approved, sutimlimab would be the first and only drug to treat CAD hemolysis.

12, dostarlimab

DoStarLimab (TS-042, GSK4057190A) is an anti-PD-1 humanized IgG4K antibody that binds to the PD-1 receptor with high affinity and effectively blocks its interaction with the ligands PD-L1 and PD-L1. The drug, an anti-PD-1 tumor immunotherapy, was developed as a result of AnaptysBio's partnership with Tesaro, which was acquired by GlaxoSmithKline (GSK) in 2019. In the first quarter of 2020, DoStarlimab's BLA and MAA were accepted by the US FDA and EU EMA, respectively, for the second-line treatment of patients with advanced or recurrent mismatched repair defect (DMMR) endometrial cancer (EC).

Currently, GSK is also evaluating dostarlimab treatment in early clinical studies all kinds of tumor, at the same time in phase III RUBY trials evaluate dostarlimab combined standard treatment (chemotherapy) treatment of recurrent or primary late women with endometrial cancer (predict to be finished in October 2021), in the study of phase III FIRST evaluate platinum-based chemotherapy plus dostarlimab + niraparib combination therapy first-line treatment of stage III or IV non mucous epithelial ovarian cancer (complete) in February 2023, is expected.

13, balstilimab

Balstilimab is an anti-PD-1 whole human IgG4K antibody developed by Agenus, Inc., in an anti-PD-1 tumor immunotherapy category. Several PD-(L)1 therapies, including Keytruda, Opdivo, Tecentriq, Libtayo, Bavencio and Imfinzi, are currently available for the treatment of various solid tumors and lymphomas. However, Agenus' clinical studies of balstilimab have focused on the treatment of cervical cancer as a monotherapy or in combination with the anti-CTLA4 treatment zalifrelimab (Agen1884). The FDA has previously granted fast-track approval for balstilimab and balstilimab/zalifrelimab for the treatment of cervical cancer.

In September 2020, Agenus has initiated the submission of balstilimab to the U.S. FDA as a monotherapy for BLA in relapsed/metastatic cervical cancer. It is worth noting that Balstilimab has exclusive rights in Greater China, Recepta Biopharma has rights in South America, and Agenus has rights in the rest of the world.

14, loncastuximab tesirine

Loncastuximab tesirine is an antibody-conjugated drug (ADC) targeting CD19 produced by conjugation of an anti-CD19 humanized IgG1K antibody via a linker to a pyrrolibenzodiazepine (PBD) dimer toxin. Once bound to CD19-expressing cells, the drug is internalized by the cell, which then releases a cytotoxin that irreversibly binds to DNA, creating strong cross-links that prevent DNA strands from separating. This disrupts essential DNA metabolic processes such as replication, and ultimately leads to cell death.

Loncastuximab tesirine, developed by ADC Therapeutics SA, was previously granted orphan drug designation by the U.S. Food and Drug Administration for the treatment of diffuse large B-cell lymphoma (DLBCL) and mantel cell lymphoma (MCL). In September 2020, ADC submitted Loncastuximab tesirine to the FDA for BLA treatment of relapsed or refractory DLBCL, which was accepted by the FDA in November, with a PDUFA target date of May 21, 2021.