. 2023 Feb 16;1(4):286–303. doi: 10.1038/s44222-023-00030-y

Table 1.

Approved and failed cytokine therapies

Cytokine	Name	Route of administration	Disease	Company	Outcome
Approved
IL-1RA	Kineret/anakinra	s.c.	Range of autoimmune disorders	Swedish Orphan Biovitrum	Approved by the FDA in 2001 and the EMA in 2002
IL-2	Proleukin/aldesleukin	i.v. (high dose) or s.c. (low dose)	Metastatic melanoma and renal cell carcinoma	Clinigen Group	Approved by the FDA in 1992
IL-2	Ontak/denileukin diftitox/IL2-diftitox	i.v.	T cell lymphoma	Eisai	Approved by the FDA in 2008^c
IL-11	Neumega/oprelvekin	s.c.	Thrombocytopaenia following myelosuppressive chemotherapy	Wyeth (now Pfizer)	Approved by the FDA in 1997^d
TNF	Beromun/tasonermin	Isolated-limb perfusion	Limb soft-tissue carcinoma	Belpharma	Approved by the EMA in 1999
G-CSF	Neupogen/filgrastim	s.c.	Neutropenia	Amgen	Approved by the FDA in 1991
	Neulasta/pegfilgrastim			Amgen	Approved by the FDA and the EMA in 2002
	Lonquex/lipegfilgrastim^a			Teva Pharmaceuticals	Approved by the EMA in 2013
GM-CSF	Leukine/sargramostim	i.v. or s.c. (after myelosuppressive radiotherapy)	Post radiotherapy and chemotherapy, and bone marrow and peripheral blood cell transplantation	Partner Therapeutics	Approved by the FDA in 1991
IFNα2a	Roferon A	s.c.	Chronic hepatitis C, hairy cell leukaemia and chronic myelogenous leukaemia	F. Hoffmann-La Roche	Approved by the FDA in 1995^d
IFNα2a	Pegasys^a	s.c.	Chronic hepatitis B and C	F. Hoffmann-La Roche	Approved by the FDA in 2002
IFNα2b	Intron A	i.v., i.m. or s.c.	Chronic hepatitis B and C, hairy cell leukemia, malignant melanoma, follicular lymphoma, Kaposi’s sarcoma and genital warts	Schering-Plough (now Merck)^b	Approved by the FDA in 1995^d
	PegIntron/Sylatron^a	s.c.	Chronic hepatitis C, melanoma	Schering-Plough (now Merck)^b	Approved by the FDA in 2001 and the EMA in 2000^e
	Besremi^a	s.c.	Polycythaemia vera	PharmaEssentia	Approved by the FDA in 2021
IFN mix	Multiferon	s.c.	Malignant melanoma	Swedish Orphan Biovitrum	Approved in several European countries since 2005
IFNβ1a	Avonex/Rebif/Cinnovex/Soluferon	i.m. or s.c.	Multiple sclerosis	Biogen, Merck^b and CinnaGen	Approved by the FDA in 1996/2002
IFNβ1a	Plegridy^a	i.m. or s.c.	Multiple sclerosis	Biogen	Approved by the FDA in 2014
IFNβ1b	Betaseron/Extavia	s.c.	Multiple sclerosis	Bayer and Novartis	Approved by the FDA in 1993
IFNγ1b	Actimmune	s.c.	Chronic granulomatous disease	Horizon Pharma	Approved by the FDA in 1990
Epoetin alfa	Epogen/Procrit	i.v. or s.c.	Anaemia	Amgen and Johnson & Johnson	Approved by the FDA in 1989
	Aranesp/darbepoetin alfa			Amgen	Approved by the FDA in 2001
	Mircera^a			F. Hoffmann-La Roche	Approved by the FDA and the EMA in 2007
	Omontys/peginesatide^a			Affymax and Takeda Pharmaceutical	Approved by the FDA in 2012^f
Epoetin beta	NeoRecormon	i.v. or s.c.	Anaemia	F. Hoffmann-La Roche	Approved by the EMA in 2001
Epoetin theta	Biopoin	s.c.	Anaemia	Teva Pharmaceuticals	Approved by the EMA in 2009
Failed
IL-4	NA	s.c.	Psoriasis	Schering-Plough (now Merck)^b	Limited clinical benefit²⁰⁷
IL-4	NA	s.c.	AIDS-related Kaposi’s sarcoma	NIAID	Limited clinical benefit²⁰⁸
IL-7	NA	s.c.	Metastatic melanoma, locally advanced or metastatic kidney cancer, refractory solid tumours	Revimmune and National Cancer Institute	Limited clinical benefit, formation of neutralizing antibodies^209,210
IL-10	Tenovil	s.c.	Crohn’s disease	Schering-Plough (now Merck)^b	No clinical benefit^211,212
IL-10	NA	i.v.	Rheumatoid arthritis	Tufts University School of Medicine	No clinical benefit and complications upon multiple dosing²¹³
IL-12	NA	i.v.	Renal cell carcinoma	Wyeth (now Pfizer)	Severe toxicity issues: 2 deaths upon high dosing³⁸
IL-15	NA	i.v.	Metastatic malignant melanoma or metastatic renal cell cancer	National Cancer Institute	Toxicity issues²¹⁴
IL-21	NA	i.v.	Recurrent or metastatic melanoma	ZymoGenetics (now Bristol Myers Squibb)	No clinical benefit²¹⁵
TRAIL	Dulanermin/AMG 951	i.v.	Colorectal cancer, non-Hodgkin’s lymphoma, non-small-cell lung cancer	Amgen and Genentech (F. Hoffmann-La Roche)	No clinical benefit and adverse events^216–218

EMA, European Medicines Agency; FDA, US Food and Drug Administration; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte–macrophage colony-stimulating factor; IFN, interferon; IL-1RA, IL-1 receptor antagonist; i.m., intramuscular; i.v., intravenous; NA, not applicable; NIAID, National Institute of Allergy and Infectious Diseases; PEG, polyethylene glycol; s.c., subcutaneous; TNF, tumour-necrosis factor; TRAIL, tumour-necrosis factor-related apoptosis-inducing ligand. ^aThese are PEGylated cytokines. ^bMerck Sharp and Dohme outside the USA and Canada. ^cDiscontinued in 2014 following manufacturing issues. ^dDiscontinued. ^eInduces severe side-effects (for example, suicidal depression). ^fDiscontinued in 2013 owing to severe adverse effects.