Clinical Trials

Date: 2013-06-12

Type of information: Presentation of results at a congress

phase: 1-2

Announcement: oral and poster presentation on ALX-0061, at the Annual European Congress of Rheumatology (EULAR), which takes place from 12 to 15 June 2013 in Madrid, Spain: 

Company: Ablynx (Belgium)

Product: ALX-0061

Action mechanism: monoclonal antibody/Nanobody. IL-6 and its receptor IL-6R are involved in the pathogenesis of various inflammatory and auto-immune diseases, including RA. ALX-0061 is a Nanobody binding to the interleukin-6 receptor (IL-6R). It has the potential to be differentiated from the benchmark monoclonal antibody through its high potency, high stability and low molecular weight of only 26kD which could translate into superior tissue penetration, attractive PK/PD and a superior safety and efficacy profile. The Nanobody is half-life extended with a Nanobody targeting albumin, which is believed to improve the delivery of the Nanobody to inflamed tissues.

Disease: rheumatoid arthritis

Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases

Country: Europe

Trial details: During the period April to September 2011, the Phase I study recruited a total of 28 RA patients who received either placebo or a single dose of ALX-0061, injected intravenously. The single doses ranged from 0.3 mg/kg to 6 mg/kg. The study treatment was safe and well tolerated, and the biological effective doses were achieved at the doses established in the pre-clinical studies. The dose-dependent changes of the assessed biomarkers of early inflammation (C-reactive protein, fibrinogen and platelets) were consistent with the inhibition of the IL-6 pathway. In the 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 3 patients were switched from placebo to ALX-0061 treatment (the 'switchers').

Latest news:

• • On June 12, 2013,  Ablynx has announced that it will have an oral and poster presentation on its novel anti-IL-6R Nanobody, ALX-0061, at the Annual European Congress of Rheumatology (EULAR), in Madrid, Spain. The oral presentation will demonstrate the strong efficacy and safety profile of 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 on a stable background of methotrexate. The pooled data at week 24 show that treatment with ALX-0061 results in an ACR20 improvement of 84% and a 58% DAS28 remission. At all doses tested, ALX-0061 was well tolerated and clinically relevant neutropenia was absent as well as serious infections. Clinically significant signals in lipids were not observed and no anti-drug antibodies were detected. The poster presentation will include data from in vitro experiments that assessed the biological activity and affinity for both the soluble and membrane-bound IL-6-receptor of ALX-0061 as compared to tocilizumab (Actemra®). The in vitro results demonstrate the preferential inhibition of soluble Il-6R trans-signalling by ALX-0061 could provide superior therapeutic efficacy with a better side effect profile than tocilizumab.
• • On February 13, 2013, Ablynx 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. At all doses tested, ALX-0061 was well-tolerated and the safety profile compared favourably to data reported for other biological DMARDs. 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 for 1mg/kg Q4W (N=8) ACR20  75%  ACR50 63%  ACR70 50% DAS28 remission 50% Boolean remission 50%
• - Efficacy parameter for 3mg/kg Q4W (N=8) ACR20 100% ACR50 75% ACR70 63% DAS28 remission 75% Boolean remission 38% 
• - Efficacy parameter for 6mg/kg Q8W (N=8) ACR20 75% ACR50 75% ACR70 63% DAS28 remission  63% Boolean remission 25%
• - Efficacy parameter for Pooled 'unmodified' (N=24) ACR20 83% ACR50 71% ACR70 58% DAS28 remission 63% Boolean remission 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 for Pooled 'modified' (N=4) ACR20 75% ACR50 50% ACR70 50% DAS28 remission 50%
• - Efficacy parameter for Pooled 'switchers' (N=3) ACR20 100% ACR50 50% 67% ACR70 0% DAS28 remission 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. The majority of patients achieved a durable status of disease remission, some of them already after the first month of treatment. In addition, patients who had an inadequate response could be identified early on in the treatment schedule and could even be 'rescued'. Ablynx is now investigating the various possibilities through which the company can progress the development of ALX-0061, including discussions with potential partners and other paths which will allow to maximise the value of this asset.
• • On November 30, 2011, Ablynx has announced positive Phase I data from the single ascending dose part of the Phase I/II study with ALX-0061, the anti-IL-6R Nanobody, in patients with rheumatoid arthritis (RA). Based on these positive interim data, Ablynx has initiated a multiple ascending dose Phase II study with ALX-0061 in patients with RA.Following the phase I study, three doses were selected for the Phase II study, including 1 mg/kg every 4 weeks, 3 mg/kg every 4 weeks, and 6 mg/kg every 8 weeks. This proof-of-concept Phase II study is expected to recruit 36 RA patients. A first read out, including efficacy measures (DAS, ACR scores) is anticipated after 12 weeks and a final read out, including biomarker responses, is planned after 24 weeks.
• •  On March 28, 2011, Ablynx has initiated a double-blind, randomised, placebo-controlled Phase I/II study with ALX-0061, a Nanobody targeting the interleukin 6 receptor (IL-6R), in patients with rheumatoid arthritis (RA). The Phase I/II study will investigate the safety, PK, PD and efficacy of single and multiple intravenous administrations of ALX-0061. Ablynx will recruit up to 72 patients with RA in up to ten centres in Europe.

Is general: Yes