Drug discovery
48
drugs
With orphan designations
Overview
Adenocarcinoma of the esophagus arises from glandular cells, primarily in the lower esophagus. It is strongly linked to chronic gastroesophageal reflux and Barrett’s metaplasia [1][5][9]. Prognosis remains poor (5-year survival: ~21.6% [14]), with most cases diagnosed at advanced stages due to late symptom onset [3][6][9]. Treatment relies on multimodal approaches, including chemoradiation, surgery, and emerging immunotherapy [1][3][5].
Burden
Accounts for ~1.1% of U.S. cancer cases (22,370 new cases in 2024) but 2.6% of cancer deaths (16,130 estimated deaths) [14]. Over 80% present with regional/distant spread, contributing to high morbidity and healthcare costs [6][10][14]. Global disparities exist, with higher mortality in underserved populations due to delayed diagnosis [2][12].
Therapies
Localized disease: Neoadjuvant chemoradiation (CROSS regimen: carboplatin/paclitaxel + 41.4 Gy radiation) followed by esophagectomy [3][7][11].
Advanced/metastatic disease: Combination chemotherapy (e.g., FLOT), immunotherapy (nivolumab, pembrolizumab), and targeted therapies (trastuzumab for HER2+) [1][7][11].
Palliation: Endoscopic stenting, brachytherapy, or laser therapy for dysphagia [1][5][7].
Categories: rare gastroenterological diseases, rare neoplastic diseases
Drug Discovery Landscape
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
an antibody-drug conjugate composed of a humanized monoclonal antibody PM-012C against fibroblast growth factor receptor 2b (FGFR2b) conjugated to exatecan (topoisomerase I inhibitor) through a cleavable linker Pym-PEG8-Val-Ala-PAB | antibodies | FDA | 2026-02-09 | — | Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd |
envafolimab | antibodies | FDA | 2025-12-12 | — | 3D Medicines (Sichuan) Co., Ltd |
7-ethtyl-10-hydroxycamptothecin and irinotecan | small molecules | FDA | 2025-12-10 | — | SN BioScience Inc. |
antibody drug conjugate consisting of PM-012D antibody and linker-payload Pym-PEG8-Val-Ala-PAB-Exd | antibodies | FDA | 2025-12-09 | — | Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd |
antibody-drug conjugate (ADC) consisting of a humanized anti-trophoblast cell surface antigen-2 (TROP2) antibody and a protease-cleavable linker-payload N-PM-0022 (BCN-GGVA-PAB(PEG24)-exatecan) | antibodies | FDA | 2025-12-04 | — | OBI Pharma USA Inc. |
oxazol 2 ylmethyl N [5 [(1R)-1-(6-methoxy-3-pyridyl)ethyl]thiazol-2-yl]carbamate | small molecules | FDA | 2025-10-22 | — | Dewpoint Therapeutics Inc. |
antibody-drug conjugate consisting of an anti-human epidermal growth factor receptor 2 bispecific antibody conjugated to a topoisomerase I inhibitor | antibodies | FDA | 2025-07-27 | — | Jiangsu Alphamab Biopharmaceuticals Co., Ltd. |
telisotuzumab adizutecan | antibodies | FDA | 2025-07-27 | — | AbbVie Inc. |
nesuparib | small molecules | FDA | 2025-03-17 | — | Onconic Therapeutics |
lenvatinib | small molecules | FDA | 2024-11-14 | — | Eisai Inc. |
antibody-drug conjugate (ADC) consisting of a humanized anti-trophoblast cell surface antigen-2 (TROP2) antibody (R4702) and a cathepsin B protease-cleavable linker-payload N-PM-0017 (MCCa-PEG24-VA-PAB-exatecan) | antibodies | FDA | 2024-08-06 | — | OBI Pharma USA Inc. |
recombinant humanized IgG1 anti-TROP2 monoclonal antibody conjugated to a topoisomerase I inhibitor | antibodies | FDA | 2024-06-18 | — | Merck, Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (MSD) |
Neratinib maleate Tablets | small molecules | FDA | 2024-03-25 | — | Convalife Pharmaceuticals Co., Ltd. |
durvalumab [Imfinzi] | antibodies | FDA | 2023-10-12 | 2025-11-25 | AstraZeneca Pharmaceuticals |
trastuzumab biosimilar conjugated with TLR7/8 via a non-cleavable linker | antibodies | FDA | 2023-09-22 | — | Bolt Biotherapeutics |
ex vivo expanded allogeneic cord blood-derived NK cells that have been genetically modified to express a HER2-directed CAR and secrete IL-15 | cell therapies | FDA | 2023-03-07 | — | Artiva Biotherapeutics, Inc. |
N-(6-(2,6-dichloro-3,5-dimethoxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-4-(3,3-dimethylpiperazin-1-yl)benzamide hydrochloride | small molecules | FDA | 2023-01-12 | — | 3D Medicines (Beijing) Co., Ltd |
Autologous Claudin18.2-targeted CAR-T cells | cell therapies | FDA | 2022-11-22 | — | Legend Biotech USA, Inc. |
Trastuzumab vedotin | antibodies | FDA | 2022-08-29 | — | Shanghai Miracogen Inc. |
Docetaxel albumin bound | small molecules | FDA | 2022-07-20 | — | Conjupro Biotherapeutics, Inc. |
A CD47-binding, fusion protein containing a high affinity engineered D1 domain of human signal regulatory protein alpha (SIRPalpha) variant 1 (v1) genetically linked to a modified and inactive Fc domain of human IgG | proteins | FDA | 2022-01-27 | — | ALX Oncology Inc. |
Humanized, Low-fucose Anti-Claudin 18.2 IgG1 Antibody with Enhanced ADCC | antibodies | FDA | 2021-07-26 | — | Suzhou Traoscenta Therapeutics Co., Ltd. |
cinrebafusp | antibodies | FDA | 2021-06-22 | — | Pieris Pharmaceuticals, Inc. |
fully human monoclonal IgG1 antibody against the type 2 isoform of human Claudin 18 protein (Claudin 18.2). | antibodies | FDA | 2021-04-06 | — | Leap Therapeutics, Inc. |
humanized HER2 targeting monoclonal antibody conjugated to a cytotoxic tubulin inhibitor amberstatin | antibodies | FDA | 2021-01-14 | — | Ambrx, Inc. |
Anti-Claudin 18.2 antibody drug conjugate comprised of a Claudin 18.2 targeting monoclonal IgG1 antibody, a linker LND1002, and monomethyl auristatin E | antibodies | FDA | 2020-11-19 | — | Elevation Oncology, Inc. |
Humanized Anti-claudin18.2 Autologous Chimeric Antigen Receptor (CAR) T Cells | cell therapies | FDA | 2020-09-30 | — | CARsgen Therapeutics Corporation |
half-life extended bispecific T cell engager (BiTE®) antibody construct designed to target both CLDN18.2 and CD3 | antibodies | FDA | 2020-07-31 | — | Amgen, Inc. |
humanized IgG4 monoclonal antibody optimized for neutralizing activity against DKK1, a secreted modulator of Wnt signaling | antibodies | FDA | 2020-06-10 | — | Leap Therapeutics, Inc |
margetuximab | antibodies | FDA | 2020-06-03 | — | MacroGenics, Inc. |
half-life extended bispecific T-cell engager antibody construct targeting MUC17 and CD3 | antibodies | FDA | 2020-06-02 | — | Amgen Inc. |
fam-trastuzumab deruxtecan-nxki [Enhertu] | antibodies | FDA | 2020-05-20 | 2021-01-15 | Daiichi Sankyo, Inc. |
tislelizumab-jsgr [Tevimbra] | antibodies | FDA | 2020-05-14 | 2024-12-26 | BeOne Medicines USA, Inc. |
crenolanib | small molecules | FDA | 2019-10-21 | — | AROG Pharmaceuticals, Inc. |
anti-human epidermal growth factor receptor 2 (HER2) antibody drug conjugate | antibodies | FDA | 2018-02-01 | — | CSPC Dophen Corporation, subsidiary within CSPC Pharmaceutical Group |
humanized immunoglobulin G1 (IgG1) T-cell bispecific (TCB) antibody targeting carcinoembryonic antigen (CEA) | antibodies | FDA | 2018-01-22 | — | Genentech, Inc. |
zanidatamab | antibodies | FDA | 2017-02-06 | — | Jazz Pharmaceuticals Ireland Limited |
nivolumab [Opdivo] | antibodies | FDA | 2016-12-20 | 2021-04-16 | Bristol-Myers Squibb Company |
Nivolumab and Ipilimumab | antibodies | FDA | 2016-12-20 | — | Bristol-Myers Squibb Company |
bemarituzumab | antibodies | FDA | 2016-06-29 | — | Amgen Inc. |
napabucasin | small molecules | FDA | 2016-06-20 | — | Boston Biomedical, Inc. |
bispecific antibody (monoclonal antibody) | antibodies | FDA | 2013-08-08 | — | Elevation Oncology, Inc. |
bispecific antibody (monoclonal antibody) | antibodies | FDA | 2013-08-08 | — | Elevation Oncology, Inc. |
pertuzumab | antibodies | FDA | 2013-07-12 | — | Genentech, Inc. |
onartuzumab | antibodies | FDA | 2013-01-23 | — | Genentech, Inc. |
lapatinib ditosylate hydrochloride | small molecules | FDA | 2009-05-29 | — | Novartis Pharmaceuticals Corp. |
DHA-paclitaxel | small molecules | FDA | 2003-05-01 | — | Luitpold Pharmaceuticals, Inc. |
Tezacitabine | small molecules | FDA | 2003-01-27 | — | Sanofi-Aventis US, Inc. |