The preclinical pharmacology of the high affinity anti-IL-6R Nanobody® ALX-0061 supports its clinical development in rheumatoid arthritis

Table 2 Pharmacokinetic parameters of the non-half-life extended anti-IL-6R domain and ALX-0061 in cynomolgus monkeys

Test item	N	t_{1/2, dominant}		t_{1/2, terminal}		AUC_inf		CL		V_ss
Test item	N	(day)		(day)		(μg/day/ml)		(ml/day/kg)		(ml/kg)
		Mean	CV %	Mean	CV %	Mean	CV %	Mean	CV %	Mean	CV %
Non-half-life extended domain i.v. 0.74 mg/kg	3	-	-	0.18	3	0.19	2	3971	2	227	27
ALX-0061 i.v. 0.4 mg/kg	3	1.73	11	0.53	6	16.3	14	24.8	14	42.8	8
ALX-0061 i.v. 2 mg/kg	3	5.00	15	1.44	9	193	5	10.4	6	53.7	7
ALX-0061 i.v. 10 mg/kg	2	6.61	11	-	-	1136	21	9.00	21	82.7	10

At day 0, three animals received the non-half-life extended domain at 0.74 mg/kg or ALX-0061 at 0.4, 2, or 10 mg/kg as a single intravenous dose, before daily subcutaneous injection with recombinant hIL-6 at 5 μg/kg for seven consecutive days. Pharmacokinetic parameters were calculated using non-compartmental analysis
i.v. = intravenous; t_{1/2, dominant} = dominant elimination half-life; t_{1/2, terminal} = terminal elimination half-life; AUC_inf = area under the concentration-time curve from time zero to infinity; CL = total body clearance; V_ss = volume of distribution at steady state. CV %: coefficient of variation; N: number of animals

ISSN: 1478-6362