Itolizumab, an anti-CD6 monoclonal antibody, as a potential treatment for COVID-19 complications

Figures & data

Figure 2. Clinical stages of COVID-19 and timing of administration of Itolizumab.

Adapted from Siddiqi HK, Mehra MR. J Heart Lung Transplantation. 2020;39(5):405–7.

Table 1. Comparison of anti-CD6 mAb, Itolizumab and Anti-IL-6 and Anti-IL-1 receptor antagonists, Tocilizumab and Anakinra.

Function	Itolizumab (anti-CD6)	Tocilizumab (anti-IL-6 receptor)	Anakinra (anti-IL-1 receptor)
Mechanism of action	Binds to CD6 receptor and blocks ALCAM mediated T-cell activation	Binds to IL-6 receptor and blocks IL-6 mediated signaling in immune cells	Binds to IL-1 receptor and blocks IL-1 mediated signaling in immune cells
Immuno-modulation by regulatory T- cells	Yes	No	No
Reduction in pro-inflammatory cytokines	Downregulation of IL-6 Downregulation of IL-2 Downregulation of TNF-α Downregulation of IL-17	Blocks signaling of IL-6 alone	Blocks signaling of IL-1 alone
Duration of action	Longer due to upstream effect on the pathway	Shorter due to a more downstream action on the pathway	Short half life of 3–4h [10]

Figure 1. Itolizumab mechanism of action.

Table 2. Most frequently occurring adverse events (in >5% of patients) in the Phase 3 study (Weeks 1–52).

System organ class Preferred term	Number of Subjects, n (%)
	Arm A, N=90	Arm B, N=90	Arm C, N=43	Total, N=223
Gastrointestinal disorders
Diarrhea	0	6 (6.7)	1 (2.3)	7 (3.1)
General disorders and administration site conditions
Infusion-related reaction (acute)	18 (20.0)	15 (16.7)	5 (11.6)	38 (17.0)
Infusion-related reaction (delayed)	2 (2.2)	5 (5.6)	1 (2.3)	8 (3.6)
Pyrexia	9 (10)	8 (8.9)	5 (11.6)	22 (9.8)
Infections and infestations
Upper respiratory tract infection	2 (2.2)	10 (11.1)	5 (11.6)	17 (7.6)
Skin and subcutaneous tissue disorders
Pruritus	3 (3.3)	5 (5.6)	4 (9.3)	12 (5.4)

n = number of patients with response; N = total number of patients.

Patients were randomized in a 2:2:1 ratio to following treatment arms: (Arm A) Itolizumab 0.4 mg/kg every week for 4 weeks, followed by 1.6 mg/kg every 2 weeks for 8 weeks; (Arm B) Itolizumab 1.6 mg/kg every 2 weeks for 12 weeks; (Arm C) placebo for 12 weeks. Arms A and B continued to receive Itolizumab at the dose of 1.6 mg/kg every 4 weeks till weeks 24; Arm C received Itolizumab at 1.6 mg/kg every 2 weeks till weeks 24. Thereafter, arm C received Itolizumab at the dose of 1.6 mg/kg every 12 weeks, and patients in arm A and B were re-randomized based on their PASI response (≥PASI 75 received either Itolizumab 1.6 mg/kg every 12 weeks or placebo till week 52; ≥PASI 50 but <PASI 75 received Itolizumab 0.4 mg/kg every week for 4 weeks followed by 1.6 mg/kg every 4 weeks).

Cavalli G, De Luca G, Campochiaro C, et al. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatol. 2020;2:e325-e331.

 PubMedGoogle Scholar