Emerging Therapies for Ulcerative Colitis: Updates from Recent Clinical Trials

Figures & data

Table 1 Summary of Advanced Therapies in Phase II/III for the Management of Ulcerative Colitis

Drug Class	Agent	Target	Mode of Delivery	Stage
Anti-TNF	CT-P13	TNF	SC	Phase III completed
	OPRX-106	TNF	Oral	Phase II completed
JAK inhibitors	Ivarmacitinib	JAK1	Oral	Phase II completed/Phase III recruiting
	Brepocitinib (PF-06700841)	JAK1/TYK2	Oral	Phase IIb completed
	Ritlecitinib (PF-06651600)	JAK3/TEC kinase inhibitor	Oral	Phase IIb completed
	Peficitinib	Pan-JAK (JAK3)	Oral	Phase IIb completed (No dose response relationship)
	Izencitinib (TD-1473)	Pan-JAK (gut selective)	Oral	Phase IIb completed (primary endpoint not met)
	Deucravacitinib (BMS-986165)	TYK2	Oral	Phase II completed (primary endpoint not met)
Anti-Trafficking Agents	Etrolizumab	α4β7 and αEβ7 integrins	SC	Phase III completed
	Carotegrast methyl (AJM300)	α4 integrin	Oral	Phase III completed
	Ontamalimab (PF-00547659)	MAdCAM	SC	Phase II completed
	Abrilumab (AMG181)	α4β7 integrin	SC	Phase II completed
	PN-943	α4β7 integrin (gut restricted)	Oral	Phase II completed (primary endpoint not met)
	PTG-100	α4β7 integrin	Oral	Phase IIa completed (primary endpoint not met)
IL-23 Inhibitors	Mirikizumab	IL23/p19 subunit	IV, SC	Phase III completed
	Risankizumab	IL23/p19 subunit	IV, SC	Phase III completed (results pending)
	Brazikumab	IL23/p19 subunit	IV, SC	Development Halted
	Guselkumab	IL23/p19 subunit	IV, SC	Phase IIb/III active
S1P Receptor Modulators	Etrasimod	S1PR1, S1PR4 and S1PR5	Oral	Phase III completed
	CBP-307	S1PR1	Oral	Phase II completed
	Amiselimod (MT-1303)	S1PR1	Oral	Phase II recruiting
PDE4 Inhibitors	Apremilast	PDE4	Oral	Phase II completed
TLR9 Agonist	Cobitolimod	TLR9	Topical (enema)	Phase IIb completed/Phase III recruiting

Abbreviations: TNF, tumor necrosis factor; JAK, janus kinase; TYK 2, tyrosine kinase 2; S1P, sphingosine 1 phosphate; S1PR, sphingosine 1 phosphate receptor; PDE4, phosphodiesterase 4; TLR9, toll-like receptor 9; α4β7, alpha4-beta7; αEβ7, alphaE-beta7; α4, alpha4; MAdCAM, mucosal addressin cell adhesion molecule-1; IL-23, interleukin 23; IV, intravenous; SC, subcutaneous.

Table 2 Summary of Emerging Therapies That Have Completed Phase III Trials

Agent	Target	Mode of Delivery	Dose	Primary Endpoint	Primary Endpoint (Drug vs Placebo)
CT-P13	TNF	SC	120 mg Q2WK	LIBERTY-UC: Clinical remission at WK 52	43.2% vs 20.8% (p<0.001)
Etrolizumab	α4β7 and αEβ7 integrins	SC	105 mg Q4WK	HICKORY: Clinical remission WK14 HICKORY: Clinical remission WK 66 HIBISCUS I: Clinical remission WK10 HIBISCUS II: Clinical remission WK10	18.5% vs 6.3% (p=0.003) 24.1% vs 20.2% (p=0.50) 19.4% vs 6.9% (p=0.017) 18.2% vs (11.1%) (p=0.17)
Carotegrast methyl (AJM300)	α4 integrin	Oral	960 mg TID	Clinical response WK8	45% vs 21% (p<0.001)
Mirikizumab	IL23/p19 subunit	IV (induction) SC (maintenance)	Induction: 300 mg Q4WK Maintenance: 200 mg Q4WK	LUCENT 1: Clinical remission WK12 LUCENT 2: Clinical remission WK40	24.2% vs 13.3% (p<0.001) 49.9% vs 25.1% (p<0.001)
Upadacitinib	JAK1	Oral	Induction: 45 mg daily Maintenance: 15–30 mg daily	U-ACHIEVE: Clinical remission WK8 U-ACCOMPLISH: Clinical remission WK 8 U-ACHIEVE (Maintenance): Clinical remission WK52	26% vs 5% (p<0.001) 33% vs 4% (p<0.001) 52% (30 mg) vs 12% (p<0.001) 42% (15 mg) vs 12% (p>0.001)
Etrasimod	S1PR1, S1PR4 and S1PR5	Oral	2 mg daily	ELEVATE UC 12: Clinical remission WK12 ELEVATE UC 52: Clinical remission WK12 ELEVATE UC 52: Clinical remission WK52	25% vs 15% (p=0.026) 27% vs 7% (p<0.001) 32% vs 7% (p<0.001)

Note: Bold= primary endpoint met.

Abbreviations: TNF, tumor necrosis factor; α4β7, alpha4-beta7; αEβ7, alphaE-beta7; α4, alpha4; IL-23, interleukin 23; JAK, janus kinase; S1PR, sphingosine 1 phosphate receptor; SC, subcutaneous; IV, intravenous; Q2WK, every 2 weeks; Q4WK, every 4 weeks; TID, three times a day; WK, week; UC, ulcerative colitis.

Figure 1 Summary of select advanced therapy classes with current development status of associated agents.

Abbreviations: SC, subcutaneous; IL, interleukin; JAK, janus kinase; TYK2, tyrosine kinase 2; S1PR, sphingosine 1 phosphate receptor; TNF, tumor necrosis factor.