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

Van Roy, Maarten; Ververken, Cedric; Beirnaert, Els; Hoefman, Sven; Kolkman, Joost; Vierboom, Michel; Breedveld, Elia; ‘t Hart, Bert; Poelmans, Sofie; Bontinck, Lieselot; Hemeryck, Alex; Jacobs, Sandy; Baumeister, Judith; Ulrichts, Hans

doi:10.1186/s13075-015-0651-0

Table 3 Overview of results obtained in the CIA study in rhesus monkeys

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

Compound	Animal ID	Day of CRP >50 mg/mL^a	CRP maximum^b (mg/ml)	Day with Clinical score = 5^c	Day of sacrifice^d	Early responder	Neutralizing or clearing ADAs (based on PK and sIL-6R)	Body weight at day of sacrifice or day 70	Swelling score at day of sacrifice or day 70
Placebo	95020	24	547.5	NA	39	No	NA	-23 %	8
Placebo	R05029	21	191.5	NA	44	No	NA	-20 %	12.5
Placebo	R05053	24	535.6	NA	52	No	NA	-25 %	37
Placebo	R05058	17	547.2	NA	38	No	NA	-25 %	14
Placebo	R05073	14	643.1	28	29	Yes (CRP)	NA
7.5 mg/kg ALX-0061	R00060	17	151.6	21	22	Yes (Cl Sc)	No
7.5 mg/kg ALX-0061	R01016	35	101.9	35	34	No	Yes (Day 34)
7.5 mg/kg ALX-0061	R02055	NA	<50	NA	70	No	No	-10 %	0
7.5 mg/kg ALX-0061	R03014	17	128.1	NA	49	No	Yes (Day 28)
7.5 mg/kg ALX-0061	R05012	21	188.9	NA	44	No	Yes (Day 34)
7.5 mg/kg ALX-0061	R05042	NA	<50	NA	70	No	No	-15 %	2
7.5 mg/kg ALX-0061	R06003	17	50.6	17	17	Yes (Cl Sc)	No
10 mg/kg tocilizumab	95031	NA	<50	NA	70	No	No	+4 %	0
10 mg/kg tocilizumab	BB226	24	367.3	28	28	No	Yes (Day 28)
10 mg/kg tocilizumab	R04042	28	448.1	31	31	No	Yes (Day 28)
10 mg/kg tocilizumab	R05059	NA	<50	NA	70	No	No	+6 %	0
10 mg/kg tocilizumab	R05061	21	453.0	31	31	No	Yes (Day 24)
10 mg/kg tocilizumab	R05089	28	161.7	NA	70	No	Yes (Day 28)
10 mg/kg tocilizumab	R05090	21	171.1	21	21	Yes (Cl Sc)	Yes (Day 21)

Treatment was started seven days after sensitization with chicken collagen type II. Animals were administered weekly for six consecutive weeks by intravenous bolus injection. ALX-0061 was given at 7.5 mg/kg, and TCZ at 10 mg/kg. Data were processed as follows: body weight was normalized to pre-dose weight (day 0); Body weight and swelling score are not included for early responders and animals which showed a clearing and/or neutralizing ADA response. Early responders were identified via CRP or clinical score. Animals which had active exposure throughout the study (that is, no neutralizing and/or clearing ADA) are highlighted in bold
^aStudy day that a CRP level of more than 50 mg/ml was measured for the first time, starting after day 10 (subsiding of the acute CFA response); increasing CRP levels after day 10 are interpretable as a sign of disease severity
^bMaximum CRP values measurable for the given animal after day 10; these concentrations are interpretable as a measure of disease severity
^cStudy day on which a maximum clinical score of five was reported; this is interpretable as a measure of disease severity, with early onset being a hard-to-treat disease course
^dAnimals with high discomfort scores had to be euthanized during the study period
ADA: anti-drug antibodies; CFA: complete freund’s adjuvant; CIA: collagen-induced arthritis; Cl Sc: clinical score; CRP: C-reactive protein; ID: identification; NA: not applicable; PK: pharmacokinetics; sIL-6R: soluble interleukin-6 receptor; TCZ: tocilizumab

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ISSN: 1478-6362

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