Drug discovery
43
drugs
With orphan designations
Overview
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma characterized by cyclin D1 overexpression via t(11;14) translocation [1][12]. Typically diagnosed at advanced stages (70-80% stage IV) [6][17], it primarily affects older adults and is incurable but manageable with therapies like BTK inhibitors, CAR T-cell therapy, and risk-adapted chemoimmunotherapy [3][9][13]. Prognosis varies by molecular risk factors (e.g., TP53 mutations, Ki-67 index) and treatment access [2][8].
Burden
Median survival: 3–5 years historically, improving with novel therapies [1][17]; high relapse rates (median OS for R/R: 9–41 months) [9].
Economic impact: Hospitalizations account for 30–50% of costs; treatment toxicity increases healthcare utilization [4][14].
Disparities: Black patients face 30% higher mortality vs. White patients, driven by access barriers [2][19].
Therapies
Frontline: Bendamustine/rituximab (older patients) or high-dose cytarabine + ASCT (younger/fit patients) ± rituximab maintenance [3][13][18].
Relapsed/Refractory: BTK inhibitors (ibrutinib, acalabrutinib), CAR T-cell therapy (brexucabtagene autoleucel), and BCL-2 inhibitors (venetoclax) [1][9][13].
Emerging: Non-chemotherapy regimens (e.g., ibrutinib + rituximab) and risk-stratified approaches [3][8].
Categories: rare hematological diseases, rare neoplastic diseases, rare transplant-related disorders
Drug Discovery Landscape
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
an antibody-drug conjugate composed of the humanized monoclonal antibody against ROR1, conjugated to MMAE through a mc-vc-PAB cleavable linker | antibodies | FDA | 2025-02-25 | — | Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd |
CAR-T cell engager protein that links the CD19-directed CAR-T cell to a B cell antigen CD20 | cell therapies | FDA | 2024-02-20 | — | Aleta Biotherapeutics |
sonrotoclax [Beqalzi] | small molecules | FDA | 2023-12-21 | 2026-05-13 | BeOne Medicines USA, Inc. |
3-tert-butyl-N-{(1R)-1-[4-(6-{6-[4-({1-[4-(2,4-dioxo-1,3-diazinan-1-yl)phenyl]piperidin-4-yl}methyl)piperazin-1-yl]pyridin-3-yl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-methylphenyl]ethyl}-1,2,4-oxadiazole-5-carboxamide | small molecules | FDA | 2023-12-05 | — | BeOne Medicines USA, Inc. |
an oral inhibitor of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) | small molecules | FDA | 2023-08-11 | — | Schrödinger, Inc. |
(+)N-hydroxy-N-(methylacylfulvene)urea | small molecules | FDA | 2023-01-03 | — | Lantern Pharma |
Glofitamab | antibodies | EMA | 2022-04-13 | — | Roche Registration GmbH |
Glofitamab | antibodies | FDA | 2022-02-22 | — | Genentech, Inc. |
Pirtobrutinib [Jaypirca] | small molecules | EMA | 2021-06-21 | — | Eli Lilly Nederland B.V. |
Orelabrutinib | small molecules | FDA | 2020-12-30 | — | InnoCare Pharma Inc. |
Humanised IgG1 monoclonal antibody against the extracellular domain of receptor tyrosine kinase-like orphan receptor 1 coupled via a proteolytically cleavable maleimidocaproyl-valine-citrulline-para-aminobenzoate linker to monomethyl auristatin E | antibodies | EMA | 2020-12-09 | — | Merck Sharp & Dohme B.V. |
pirtobrutinib [Jaypirca] | small molecules | FDA | 2020-08-28 | 2023-01-27 | Loxo Oncology, Inc. |
Antibody-drug conjugate (ADC) comprising an anti-ROR1 monoclonal antibody (UC-961), a proteolytically cleavable maleimidocaproyl-valine-citrulline-para-aminobenzoate linker (mc-vc-PAB), and a monomethyl auristatin E (MMAE) cytotoxin. | antibodies | FDA | 2020-08-26 | — | Merck Sharp & Dohme, LLC |
cirmtuzumab | antibodies | FDA | 2020-06-22 | — | Ho’ola Therapeutics Inc. |
Allogeneic gene-edited CD19-directed CAR T cells/azercabtagene zapreleucel | cell therapies | FDA | 2020-05-13 | — | Imugene Limited |
lisocabtagene maraleucel [Breyanzi] | cell therapies | FDA | 2020-04-01 | 2024-05-30 | Juno Therapeutics, Inc. |
Autologous peripheral blood T cells CD4 and CD8 selected and CD3 and CD28 activated transduced with retroviral vector expressing anti CD19 CD28/CD3-zeta chimeric antigen receptor and cultured [Tecartus] | cell therapies | EMA | 2019-11-13 | 2020-12-15 | Kite Pharma EU B.V. |
allogeneic gene edited CD20-directed CAR (Chimeric Antigen Receptor) T cells | cell therapies | FDA | 2019-09-11 | — | Precision BioSciences, Inc. |
parsaclisib | small molecules | FDA | 2019-06-12 | — | Incyte Corporation |
Fully human immunoglobulin G1 monoclonal antibody that targets CD32b | antibodies | FDA | 2019-01-29 | — | BioInvent International AB |
Venetoclax [Venclyxto] | small molecules | EMA | 2017-12-12 | — | Abbvie Deutschland GmbH & Co. KG |
venetoclax | small molecules | FDA | 2017-08-31 | — | AbbVie Inc. |
Humanized monoclonal immunoglobulin G1 antibody directed against human CD19 conjugated to SG3199 through a protease cleavable valine-alanine linker | antibodies | FDA | 2017-06-08 | — | ADC Therapeutics SA |
7-benzyl-4-(2-methylbenzyl)-1,2,6,7,8,9-hexahydroimidazo[1,2-a]pyrido[3,4-e]pyrimidin-5(4H)-one-2HCL | small molecules | FDA | 2017-02-07 | — | Chimerix, Inc. |
zanubrutinib [BRUKINSA] | small molecules | FDA | 2016-06-23 | 2019-11-14 | BeOne Medicines USA, Inc. |
brexucabtagene autoleucel [TECARTUS™] | cell therapies | FDA | 2016-04-28 | 2020-07-24 | Kite Pharma, Inc. |
Acalabrutinib | small molecules | EMA | 2016-03-21 | — | Acerta Pharma B.V. |
Axicabtagene ciloleucel [Yescarta] | cell therapies | EMA | 2015-10-09 | — | Kite Pharma EU B.V. |
acalabrutinib [CALQUENCE] | small molecules | FDA | 2015-09-21 | 2017-10-31 | Acerta Pharma, LLC (a member of the AstraZeneca Group) |
daratumumab | antibodies | FDA | 2015-08-20 | — | Janssen Research & Development, LLC |
triterpenoid saponin | small molecules | FDA | 2014-07-23 | — | Avicin Therapeutics, Ltd. |
Ibrutinib [Imbruvica] | small molecules | EMA | 2013-03-12 | — | Janssen Cilag International |
ibrutinib [Imbruvica] | small molecules | FDA | 2012-12-03 | 2013-11-13 | Pharmacyclics, LLC |
DNA plasmid vector expressing eIF5Ak50R protein, siRNA directed against the native eIF5A mRNA, and PEI (polyethyleneimine) | gene therapies | FDA | 2012-07-24 | — | Senesco Technologies, Inc. |
bortezomib [Velcade] | small molecules | FDA | 2012-05-30 | 2006-12-08 | Takeda Pharmaceuticals U.S.A., Inc. |
Lenalidomide [Revlimid] | small molecules | EMA | 2011-10-27 | — | Celgene Europe B.V. |
Autologous tumor-derived immunoglobulin idiotype coupled to keyhole limpet haemocyanin | vaccines | EMA | 2011-02-23 | — | Biovest Europe Limited |
Niraparib tosilate monohydrate [MK-4827] | small molecules | EMA | 2010-10-01 | — | Tesaro UK Limited |
dasiprotimut-T | vaccines | FDA | 2010-06-17 | — | Biovest International, Inc. |
lenalidomide [Revlimid] | small molecules | FDA | 2009-04-27 | 2013-06-05 | Celgene Corporation |
Temsirolimus [Torisel] | small molecules | EMA | 2006-11-06 | — | Pfizer Europe MA EEIG |
Recombinant histidine-tagged idiotype immunoglobulin Fab fragment of clonal B-cell receptors | proteins | EMA | 2004-12-21 | — | CellGenix GmbH |
Blinatumomab | antibodies | EMA | 2003-12-01 | — | Amgen Europe B.V. |