leucovorin

Small moleculeapproved

Approved

Jun 20, 1952

Leucovorin is a compound similar to folic acid, which is a necessary vitamin. It has been around and in use for many decades. Leucovorin is a medication frequently used in combination with the chemotherapy drugs fluoruracil and methotrexate. Leucovorin is not a chemotherapy drug itself, however it is used in addition to these chemotherapy drugs to enhance anticancer effects (with fluorouracil) or to help prevent or lessen side effects (with methotrexate). Leucovorin is also used by itself to treat certain anemia problems when folic acid deficiency is present. — NCATS

Clinical trial activity

1,864 trials · 896 clinical orgs · 31 marketing orgs

Phase 1

389

Phase 2

1465

Phase 3

452

Phase 4

Earliest trial started Feb 1, 1989 (NCT00002463)

Timeline

1950s

Jun 20, 1952
Earliest FDA Approval
Jun 20, 1952
Hospira — NDA Secondary Org

1980s

Feb 8, 1980
Xanodyne Pharmaceuticals — NDA Secondary Org
Jan 2, 1987
Elkins Sinn — Marketing Organization
Mar 4, 1987
Xanodyne Pharmaceuticals — Marketing Organization
Sep 14, 1987
West-Ward Pharmaceutical — Marketing Organization
Sep 24, 1987
Barr Laboratories — Marketing Organization
Jan 1, 1989
Earliest Phase 2 Sponsor(trial)
Jan 1, 1989
Earliest Phase 3 Sponsor(trial)

1990s

Feb 22, 1993
Hikma — Marketing Organization
Sep 28, 1993
Teva — Marketing Organization
Jan 1, 1995
Earliest Phase 1 Sponsor(trial)
Apr 17, 1997
Pharmachemie Bv — Marketing Organization
Jun 25, 1997
Hospira — Marketing Organization
Aug 28, 1997
Epic Pharma Llc — Marketing Organization
Feb 26, 1999
Fresenius — Marketing Organization
Mar 24, 1999
Ani Pharmaceuticals — Marketing Organization

2000s

Jan 31, 2001
Lutipold — Marketing Organization
Jan 31, 2001
Sankyo — Marketing Organization

2010s

Sep 6, 2012
Sagent Pharmaceuticals, Inc. — Marketing Organization
May 19, 2017
Mylan — Marketing Organization
Oct 26, 2017
Nichi-Iko Pharmaceutical Co., Ltd. — Marketing Organization
Nov 23, 2018
Ingenus Pharmaceuticals — Marketing Organization

2020s

Jul 30, 2020
RiconPharma — Marketing Organization
Jul 30, 2020
Novast Labs — Marketing Organization
Oct 22, 2020
Leading Pharma Llc — Marketing Organization
Jul 10, 2023
Hainan Poly Pharm — Marketing Organization
Jul 19, 2023
KINDOS — Marketing Organization
Jul 19, 2023
Meitheal — Marketing Organization
Nov 12, 2025
Gland Pharma Ltd — Marketing Organization
Feb 3, 2026
AVYXA HOLDINGS — Marketing Organization

Indications

Approved for

Studied for

Mechanism of action

Bifunctional dihydrofolate reductase-thymidylate synthaseACTIVATOR
DHFR-TS activator
- Bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) ↗
Thymidylate synthaseINHIBITOR
TYMS inhibitor
- Thymidylate synthase (TYMS) ↗

Approval history

approvedPriority reviewJun 20, 1952

Chemistry & pharmacology

Loading structure…

SMILES

NC1=NC(=O)C2=C(NCC(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)N2C=O)N1

Mol. weight: 473.4393 g/mol
Lipinski Ro5: 1 violation(s)
Rule of 3: No
Chirality: Racemic Mixture
Inorganic: No
Polymer: No
Delivery: Oral, Parenteral
Availability: Prescription Only

Oral

Yes

Parenteral

Yes

Topical

Sources

Also known as

10-formyl-7,8-dihydrofolic acid
10-formyl-7,8-dihydrofolic acid
10-formyl-7,8-dihydrofolic acid
13c5-calcium-l-leucovorin
5-formyl-5,6,7,8-tetrahydrofolic acid
5-formyl-5,6,7,8-tetrahydrofolic acid
(5-formyl-5,6,7,8-tetrahydropteroyl)glutamate
(5-formyl-5,6,7,8-tetrahydropteroyl)glutamate
5-formyl-5,6,7,8-tetrahydropteroyl-l-glutamic acid
5-formyl-5,6,7,8-tetrahydropteroyl-l-glutamic acid
5-formyltetrahydrofolate
5-formyltetrahydrofolate
5-formyltetrahydrofolate
5-formyltetrahydrofolic acid
5-formyltetrahydrofolic acid
acide folinique
acide folinique
calc folinate
calcium folinate
calcium folinate
calcium folinate
calcium folinate
calcium folinate pentahydrate
calcium laevulate
calcium leucovorin
calcium leucovorin
calcium levulate
calcium levulinate
calcium levulinate
calcium levulinate
calcium levulinate
calcium levulinate
citrovoram
citrovorum
citrovorum
citrovorum factor
citrovorum factor
citrovorum factor
diasporal
f-d folic acid
folacal
folfiri
folfiri
folfirinox
folfox
folfox
folfox-4
folfox-4
folinate
folinate
folinate
folinate-sf calcium
folinate-sf calcium
folinic acid
folinic acid
folinic acid
folinic acid
folinic acid
folinic acid calcium
folinic acid calcium salt
folinic acid calcium salt pentahydrate
follinic acid
fusilev
fusilev
fusilev
isovorin
isovorin
l(-)-5-formyl-5,6,7,8-tetrahydrofolic acid
l(-)-5-formyl-5,6,7,8-tetrahydrofolic acid
leucovirin
leucovorin
leucovorin
leucovorin
leucovorin
leucovorin
leucovorin
leucovorin
leucovorin
leucovorin calcium
leucovorin calcium
leucovorin calcium
leucovorin calcium
leucovorin calcium
leucovorinum
leucovorinum
levulinic acid
levulinic acid
levulinic acid
levulinic acid, ammonium salt
levulinic acid, calcium salt
levulinic acid, sodium salt
magnesium diasporal
magnesium diasporal
magnesium laevulinate
magnesium levulinate
magnesium levulinate
magnesium levulinate
magnesium levulinate
n5-formyl-5,6,7,8-tetrahydrofolic acid
n5-formyl-5,6,7,8-tetrahydrofolic acid
n-(5-formyl-5,6,7,8-tetrahydropteroyl)-l-glutamic acid
n-(5-formyl-5,6,7,8-tetrahydropteroyl)-l-glutamic acid
n5-formyltetrahydrofolic acid
n5-formyltetrahydrofolic acid
natriumfolinate
sodium folinate
sodium folinate
sodium folinate
sodium folinate
sodium folinate
sodium folinate
sodium folinate
wellcovorin
wellcovorin
wellcovorin

Clinical trials

NCT ID	Phase	Start date	Sponsor(s)
NCT07271355	Phase 3	Jul 1, 2026	City of Hope National Medical Center, National Cancer Institute (NCI)
NCT07283705	Phase 2	May 18, 2026	Bristol-Myers Squibb, University of Texas at Houston
NCT07221149	Phase 2/Phase 3 (Phase 3)	Mar 9, 2026	Biontech, Bristol-Myers Squibb
NCT07221357	Phase 2/Phase 3 (Phase 3)	Mar 4, 2026	Biontech, Bristol-Myers Squibb
NCT07290985	Phase 2	Mar 1, 2026	American Association for Cancer Research, Jazz Pharmaceuticals
NCT06978062	Phase 1	Feb 20, 2026	European Organisation for Research and Treatment of Cancer, Johannes Gutenburg University, University of Mannheim, University of Oxford
NCT07284849	Phase 3	Feb 16, 2026	Incyte
NCT07283848	Phase 2	Feb 1, 2026	Arcus Biosciences, Inc., Gateway for Cancer Research, Harvard University
NCT06998940	Phase 3	Jan 6, 2026	National Cancer Institute (NCI), SWOG Cancer Research Network
NCT07004413	Phase 3	Jan 1, 2026	Humboldt University
NCT07298772	Phase 1/Phase 2 (Phase 2)	Dec 31, 2025	Suzhou Suncadia Biopharmaceuticals Co., Ltd.
NCT07229846	Phase 2	Dec 31, 2025	Harbin Medical University
NCT07238283	Phase 3	Dec 31, 2025	Hengrui Therapeutics, Inc.
NCT07255404	Phase 2	Dec 31, 2025	Biontech, Bristol-Myers Squibb
NCT06783491	Phase 3	Dec 31, 2025	Spanish Association of Surgeons (AEC), Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD), Universidad de Cordoba
NCT07150403	Phase 2	Dec 31, 2025	Federation Francophone de Cancerologie Digestive
NCT06967987	Phase 2	Dec 30, 2025	Institut de Cancerologie de l'Ouest Paul Papin
NCT07277842	Phase 3	Dec 29, 2025	Sun Yat-Sen University
NCT07235202	Phase 1/Phase 2 (Phase 2)	Dec 22, 2025	Government of China
NCT07283367	Phase 1/Phase 2 (Phase 2)	Dec 19, 2025	Jiangsu Hansoh Pharmaceutical Co., Ltd.

Showing 20 of 1,864 trials

Page 1 / 94

Organizations

Research & Development (896)

Organization	Org type	Trials	As lead sponsor	Phases	Earliest year
National Cancer Institute (NCI)	Government	300	142	5	1989
Sun Yat-Sen University	Academic/Hospital	88	86	3	2011
Fudan University	Academic/Hospital	64	50	4	2006
Sanofi	For profit	51	15	3	1997
Harvard University	Academic/Hospital	46	30	3	1994
Roche	For profit	43	24	4	1992
Cornell University	Academic/Hospital	42	31	4	1990
University of Texas at Houston	Academic/Hospital	41	30	4	1989
Amgen	For profit	39	17	3	2002
Federation Francophone de Cancerologie Digestive	Academic/Hospital	36	27	2	1993
Bristol-Myers Squibb	For profit	35	17	3	2003
Pfizer	For profit	32	18	3	1999
Chinese Academy of Medical Sciences	Academic/Hospital	30	20	4	2009
Genentech	For profit	30	15	4	2005
UNICANCER	Academic/Hospital	30	25	2	1998
Zhejiang University	Academic/Hospital	28	21	5	2010
Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)	Academic/Hospital	26	22	3	1998
Merck	For profit	26	14	3	2005
Jiao Tong University	Academic/Hospital	25	18	5	2009
Mayo Clinic	Academic/Hospital	25	9	3	1993

896 organizations

Page 1 / 45

Marketing (40)

Organization	Org type	Relationship	Date
AVYXA HOLDINGS	For profit	MKTG	Feb 3, 2026
Abbott	For profit	NDA	—
Abic	For profit	MKTG	—
Abraxis	For profit	MKTG	—
Ani Pharmaceuticals	For profit	MKTG	Mar 24, 1999
Ani Pharmaceuticals	For profit	SYN	Mar 24, 1999
Athenex, Inc.	For profit	MKTG	—
Barr Laboratories	For profit	MKTG	Sep 24, 1987
Elkins Sinn	For profit	MKTG	Jan 2, 1987
Epic Pharma Llc	For profit	MKTG	Aug 28, 1997
Fresenius	For profit	MKTG	Feb 26, 1999
Gland Pharma Ltd	For profit	MKTG	Nov 12, 2025
GlaxoSmithKline	For profit	NDA2	—
GlaxoSmithKline	For profit	MKTG	—
Hainan Poly Pharm	For profit	MKTG	Jul 10, 2023
Hikma	For profit	MKTG	Feb 22, 1993
Hikma	For profit	SYN	Sep 14, 1987
Hospira	For profit	NDA2	Jun 20, 1952
Hospira	For profit	MKTG	Jun 25, 1997
Ingenus Pharmaceuticals	For profit	MKTG	Nov 23, 2018
KINDOS	For profit	MKTG	Jul 19, 2023
Leading Pharma Llc	For profit	MKTG	Oct 22, 2020
Leading Pharma Llc	For profit	SYN	Oct 22, 2020
Lutipold	For profit	MKTG	Jan 31, 2001
Meitheal	For profit	MKTG	Jul 19, 2023
Mylan	For profit	MKTG	May 19, 2017
Nichi-Iko Pharmaceutical Co., Ltd.	For profit	MKTG	Oct 26, 2017
Novast Labs	For profit	MKTG	Jul 30, 2020
Par Pharmaceuticals	For profit	MKTG	—
Pharmachemie Bv	For profit	SYN	Mar 28, 1997
Pharmachemie Bv	For profit	MKTG	Apr 17, 1997
RiconPharma	For profit	MKTG	Jul 30, 2020
Sagent Pharmaceuticals, Inc.	For profit	MKTG	Sep 6, 2012
Sagent Pharmaceuticals, Inc.	For profit	SYN	Oct 26, 2017
Sankyo	For profit	MKTG	Jan 31, 2001
Teva	For profit	MKTG	Sep 28, 1993
Teva	For profit	SYN	Sep 28, 1993
West-Ward Pharmaceutical	For profit	MKTG	Sep 14, 1987
Xanodyne Pharmaceuticals	For profit	NDA2	Feb 8, 1980
Xanodyne Pharmaceuticals	For profit	MKTG	Mar 4, 1987