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Ablynx (Euronext Brussels: ABLX) has announced efficacy and safety data for its anti-IL-6R Nanobody, ALX-0061, at the 24 week final analysis of the Phase II part of a combined Phase I/II study in patients with moderately to severely active rheumatoid arthritis (RA) on a stable background of methotrexate.
In this Phase II part, 37 RA patients were recruited and were randomised to three dose groups of intravenously administered ALX-0061 (1mg/kg Q4W[1], 3mg/kg Q4W and 6mg/kg Q8W1) or to placebo. A total of 34 patients were eligible for determination of efficacy parameters at the 12 week interim period, and all these patients continued the study until week 24.
Depending on the patient’s disease status at week 10, the monthly dose was increased (from 1mg/kg to 3mg/kg; or from 3mg/kg to 6mg/kg) or the dosing regimen intensified (from 6mg/kg Q8W to 6 mg/kg Q4W), and patients on placebo could start monthly ALX-0061 treatment at 3mg/kg. The vast majority of patients (86%, n=24) completed the study at their ALX-0061 starting regimen (the ‘unmodified’ group), for 4 patients the dosing regimen was modified (the ‘modified’ group) and three patients were switched from placebo to ALX-0061 treatment (the ‘switchers’).
At all doses tested, ALX-0061 was well-tolerated and the safety profile compared favourably to data reported for other biological DMARDs.[2] No clinically relevant neutropenia (moderate or severe decrease in neutrophils, a type of white blood cell), no clinically significant increases in lipid levels (cholesterol and triglycerides) were observed, and there were no serious infections. Infrequent elevation of liver enzymes were reported; the events were transient, generally mild to moderate, and did not result in a discontinuation of the treatment. Additionally, the side effect profile of ALX-0061 did not change with increased dose or treatment duration and no anti-drug antibodies were detected.
The efficacy results for the ‘unmodified’ patient population at week 24 are presented below:
Efficacy parameter
ACR20[3]
ACR50
ACR70
DAS28 remission[4]
Boolean remission[5]
1mg/kg Q4W (n=8)
75%
63%
50%
50%
25%
3mg/kg Q4W (n=8)
100%
75%
63%
75%
38%
6mg/kg Q8W (n=8)
75%
75%
63%
63%
25%
Pooled ‘unmodified'(n=24)
83%
71%
58%
63%
29%
The efficacy results at week 24 for the ‘modified’ patient population and patients switching from placebo to ALX-0061 treatment are presented below:
Efficacy parameter
ACR20
ACR50
ACR70
DAS28 remission
Pooled ‘modified’ (n=4)
75%
50%
50%
50%
Pooled ‘switchers’ (n=3)
100%
67%
0%
33%
A magnetic resonance imaging (MRI) assessment was also included in this study. At week 24, there was a reduction of bone oedema, which is an early indicator of joint destruction. Additionally, the global radiographic score confirmed the absence of disease progression at this final time point.
References
- Q4W: every 4 weeks – Q8W: every 8 weeks
- DMARDs: disease modifying anti-rheumatoid arthritis drugs
- ACR (American College of Rheumatology) criteria measure improvement in tender or swollen joint counts and improvement in three of five other disease-activity measures; ACR20 measures % of patients with 20% improvement; ACR50 measures % of patients with 50% improvement and ACR70 measures % of patients with 70% improvement
- DAS28 is an RA disease activity score based on C-reactive protein (CRP), tender and swollen joint counts of 28 defined joints and physician’s global health assessment; a total score of >5.1 is associated with high disease activity, moderate from 3.2 to 5.1, low disease activity from 3.2 to 2.6, and remission of disease if <2.6
- Boolean remission in RA is a more recent measure of disease activity and is achieved when at any time point, a patient satisfies all of the following: swollen and tender joint count, patient global assessment and CRP all less than or equal to 1.
