Drug discovery
35
drugs
With orphan designations
Overview
Adult hepatocellular carcinoma (HCC) is the most common primary liver malignancy, typically arising in the setting of chronic liver disease or cirrhosis, often driven by hepatitis B/C, alcohol-related liver disease, or metabolic dysfunction-associated steatotic liver disease (MASLD). Diagnosis relies on imaging (CT/MRI) and biomarker evaluation (e.g., α-fetoprotein), with histological confirmation reserved for ambiguous cases. Advanced stages present with complications such as vascular invasion, extrahepatic spread, or hepatic decompensation, necessitating multidisciplinary management [1][4][9][13].
Burden
Accounts for >80% of primary liver cancers globally, with rising incidence linked to MASLD and obesity [4][10][14].
In the U.S., annual deaths exceed 30,000, with 5-year survival <20% for advanced cases [10][17].
Disproportionately impacts socioeconomically disadvantaged populations, with care costs amplified by late-stage diagnoses and complex therapies [6][14][18].
Therapies
Early-stage: Curative options include surgical resection, liver transplantation, or ablation (radiofrequency/microwave) [5][12][15].
Intermediate-stage: Transarterial chemoembolization (TACE) or combined locoregional-systemic therapies (e.g., LEN-TACE sequential therapy) [7][12][15].
Advanced-stage: First-line systemic therapies include atezolizumab/bevacizumab or durvalumab/tremelimumab; kinase inhibitors (sorafenib, lenvatinib) remain alternatives [3][7][11][12].
Categories: rare hepatic diseases, rare neoplastic diseases, rare transplant-related disorders
Drug Discovery Landscape
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
IgG-based bispecific antibody targeting GPC3 and 4-1BB | antibodies | FDA | 2026-03-23 | — | BeOne Medicinces, USA, Inc. |
anti-TM4SF5 monoclonal antibody | antibodies | FDA | 2025-12-12 | — | ReCerise Therapeutics |
recombinant humanized IgG1 monoclonal antibody targeting human glypican-3 (GPC3) protein conjugated with exatecan via the MCC-AAQ linker | antibodies | FDA | 2025-12-09 | — | Lepu Biopharma Co., Ltd. |
recombinant human IL12/15-PDL1B HSV-1 oncolytic virus injection | other | FDA | 2025-11-19 | — | Virogin Biotech Canada Ltd |
salsalate | small molecules | FDA | 2025-11-17 | — | J & D Pharmaceuticals LLC |
messenger ribonucleic acid (mRNA) encoding for GPC3xCD3 bispecific T-cell engagers, encapsulated in lipid nanoparticle (LNP) | RNAs | FDA | 2025-11-14 | — | Beijing Jitai Life Sciences Ltd. |
Sodium 2-(3'(-3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-4-ethoxy-[1,1'-biphenyl]-3-yl)acetate | small molecules | EMA | 2025-06-20 | — | Pharma Gateway AB |
peripheral blood mononuclear cell (PBMC) derived allogeneic natural killer (NK) cell | cell therapies | FDA | 2025-05-15 | — | Shenzhen Celconta Life Science Co.Ltd |
anti-translationally controlled tumor protein (TCTP) monoclonal antibody | antibodies | FDA | 2025-03-05 | — | NEX-I, Inc. |
GPC3-CD89 mRNA-LNP: anti-GPC3-CD89 mRNA encapsulated within lipid nanoparticles | RNAs | FDA | 2025-01-31 | — | Create Medicines |
PPARalpha inhibitor | small molecules | FDA | 2024-12-16 | — | Tempest Therapeutics |
bclnstabtide | other | FDA | 2024-11-25 | — | Zhuhai Fuzhu Mingsheng Biopharmaceutical Co., Ltd |
N-[3-(azepan-1-yl)propyl]-1-{[2-(4-chlorophenyl)-5-methyl-1,3-oxazol-4-yl]methyl}piperidine-4-carboxamide | small molecules | FDA | 2024-11-25 | — | VM Discovery, Inc. |
N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-2,4-methano-1,8-naphthyridine-1(2H)-carboxamide 2-hydroxypropane-1,2,3-tricarboxylate | small molecules | FDA | 2024-11-04 | — | BroadenBio Co., Ltd. |
Tremelimumab [Imjudo] | antibodies | EMA | 2020-12-09 | — | AstraZeneca AB |
Tislelizumab | antibodies | EMA | 2020-04-22 | — | Beone Medicines Ireland Limited |
Mertansine functionalised gold nanoconjugate | small molecules | EMA | 2018-02-22 | — | [INACTIVE] Midatech Pharma Espana S.L. |
Florilglutamic acid (18F) | small molecules | EMA | 2016-03-21 | — | [INACTIVE] Lantheus Germany GmbH |
fisogatinib | small molecules | FDA | 2015-09-14 | — | Blueprint Medicines Corporation |
nivolumab [OPDIVO] | antibodies | FDA | 2015-09-02 | 2017-09-22 | Bristol-Myers Squibb Company |
nivolumab [Opdivo] | antibodies | FDA | 2015-09-02 | 2025-04-11 | Bristol-Myers Squibb Company |
Lenvatinib mesilate [Lenvima] | small molecules | EMA | 2015-03-19 | — | Eisai GmbH |
Tivantinib [Enriav] | small molecules | EMA | 2013-11-13 | — | Neuway Pharma GmbH |
Galunisertib monohydrate [TGF-beta R1 Kinase Inhibitor (LY2157299)] | small molecules | EMA | 2013-03-12 | — | Eli Lilly Nederland B.V. |
Ramucirumab | antibodies | EMA | 2012-07-04 | — | Eli Lilly Nederland B.V. |
Brivanib alaninate | small molecules | EMA | 2011-10-27 | — | [INACTIVE] Bristol-Myers Squibb Pharma EEIG |
human tumor necrosis factor coupled to the C terminus of CNGRCG peptide | proteins | FDA | 2009-10-01 | — | Molecular Medicine S.p.A. (Molmed) |
Linifanib [Linifanib] | small molecules | EMA | 2007-12-20 | — | Abbvie Limited |
Amsilarotene | small molecules | EMA | 2007-10-22 | — | [INACTIVE] Gendux Molecular Limited |
Sulfonated monophosphorylated mannose oligosaccharide | small molecules | EMA | 2007-09-14 | — | [INACTIVE] SRA Global Clinical Development Limited |
Sorafenib tosilate [Nexavar] | small molecules | EMA | 2006-04-11 | — | Bayer AG |
Doxorubicin hydrochloride [Doxorubicin Transdrug] | small molecules | EMA | 2004-10-21 | — | Onxeo |
Nolatrexed dihydrochloride [Thymitaq] | small molecules | EMA | 2003-10-02 | — | [INACTIVE] Harrison Clinical Research Limited |
CHARCOAL, ACTIVATED, Doxorubicin hydrochloride, Iron [MTC-DOX for Injection] | small molecules | EMA | 2002-09-11 | — | [INACTIVE] Interface International Consultancy Limited |
Seocalcitol | small molecules | EMA | 2001-07-31 | — | LEO PHARMA A/S |