Table 2.

Drugs in clinical trials targeting the S1P axis

Drug	Mechanism of action	Indications	ClinicalTrials.gov identifier	Phase
Fingolimod (Gilenya; Novartis)	S1PR modulator, S1PR1 functional antagonist	Relapsing–remitting multiple sclerosis	-	Approved
		Acute, non-infectious intermediate, posterior and pan-uveitis	NCT01791192	II
		Amyotrophic lateral sclerosis	NCT01786174	II
		Schizophrenia	NCT01779700	I
		Acute demyelinating optic neuritis	NCT01757691	II
		Relapsing–remitting multiple sclerosis with depression, in combination with antidepressants	NCT01436643	IV
		Chronic inflammatory demyelinating polyradiculoneuropathy	NCT01625182	III
		Kidney transplant	NCT00099801	III
Safingol	Sphingosine derivative, PKC inhibitor	Solid tumours, combined with fenretinide	NCT01553071	I
		Solid tumours, combined with cisplatin	NCT00084812	I (completed)
Sonepcizumab	S1P-specific monoclonal antibody	Exudative age-related macular degeneration	NCT01414153	II
		Pigment epithelial detachment	NCT01334255	I (terminated)
		Neovascular age-related macular degeneration	NCT00767949	I
		Solid tumours	NCT00661414	I (completed)
		Unresectable and refractory renal cell carcinoma	NCT01762033	II
ABC294640	SPHK2 inhibitor	Pancreatic cancer	NCT01488513	I
KRP203	S1PR1 agonist	Sub-acute cutaneous lupus erythematosus	NCT01294774	II (terminated)
		Ulcerative colitis	NCT01375179	II (terminated)
		Haematological malignancies	NCT01830010	I
Siponimod (BAF312)	S1PR1 and S1PR5 modulator	Hepatic impairments	NCT01565902	I
		Relapsing–remitting multiple sclerosis	NCT00879658	II
		Relapsing–remitting multiple sclerosis	NCT01185821	II
		Secondary progressive multiple sclerosis	NCT01665144	III
		Polymyositis, dermatomyositis	NCT01148810	II (terminated)
RPC1063	S1PR1 modulator	Relapsing–remitting multiple sclerosis	NCT01628393	II
		Ulcerative colitis	NCT01647516	II
ONO-4641	S1PR1 and S1PR5 agonist	Multiple sclerosis	NCT01226745	II
LX3305	S1P lyase inhibitor	Rheumatoid arthritis	NCT00847886	I (completed)
		Rheumatoid arthritis	NCT00903383	II (completed)
GSK2018682	S1PR1 agonist	Relapsing–remitting multiple sclerosis	NCT01466322	I (completed)
		Relapsing–remitting multiple sclerosis	NCT01431937	I (completed)
Ponesimod ACT-128800	S1PR1 agonist	Plaque psoriasis	NCT00852670	II (completed)
		Relapsing–remitting multiple sclerosis	NCT01093326	II
		Psoriasis	NCT01208090	II (completed)
		Relapsing–remitting multiple sclerosis	NCT01006265	II (completed)

PKC, protein kinase C; S1P, sphingosine-1-phosphate; S1PR, S1P receptor; SPHK, sphingosine kinase.