Clinical Trials

Date: 2014-10-23

Type of information: Results

phase: 1

Announcement: results

Company: Ablynx (Belgium) AbbVie (USA - IL)

Product: ALX-0061

Action mechanism: ALX-0061 is a Nanobody targeting the interleukin 6 pathway via its IL-6 receptor (IL-6R), which plays a key role in the inflammation process in rheumatoid arthritis. ALX-0061 has been designed to become a best-in-class therapeutic. Its small size (26kD) may potentially allow ALX-0061 to penetrate more effectively into tissues. The potent, monovalent interaction of the molecule with its target reduces the possibility of off-target effects. Its binding to human serum albumin prolongs the in vivo half-life of the product and can lead to improved trafficking to areas of inflammation. The Nanobody has a very strong affinity for soluble IL-6R which should ensure fast target engagement and could result in a fast onset of effect.

Disease:

inflammatory diseases, including rheumatoid arthritis and systemic lupus erythematosus

Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases

Country: The Netherlands

Trial details: The Phase I study involves a single-centre, open-label trial to evaluate the bioavailability of ALX-0061 after sc and intravenous (iv) administration in healthy volunteers. In addition, the study will assess the pharmacodynamics, safety, tolerability and immunogenicity of single sc and iv doses of ALX-0061 in healthy subjects. The trial is expected to recruit 70 subjects who will each receive a single dose of ALX-0061, either as a sc injection (50 mg, 150 mg or 300 mg dose) or iv infusion (50 mg or 300 mg dose). (NCT02101073)

Latest news:

• •  On October 23, 2014, Ablynx announced positive results from the Phase I bioavailability study of the subcutaneous formulation of its anti-IL-6R Nanobody®, ALX-0061, for the treatment of inflammatory diseases, including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Bioavailability after subcutaneous administration was higher than 80% and there were no significant safety or tolerability signals noted with subcutaneous administration of ALX-0061. The Phase I study in healthy adult volunteers evaluated the bioavailability of single doses of ALX-0061, administered sc at three dose levels (50 mg, 150 mg and 300 mg dose), using two corresponding single intravenous (iv) dose levels (50 mg and 300 mg) as reference. In addition, the study assessed the pharmacodynamics, safety, tolerability and immunogenicity of single sc and iv doses of ALX-0061. A total of 70 subjects were included in the five treatment arms, with 14 subjects in each arm.
• These results demonstrate that ALX-0061 exhibits a bioavailability of more than 80% when given subcutaneously to healthy subjects. Maximum mean ALX-0061 serum concentrations, following sc administration, were reached after approximately one to three days post dose. Mean serum IL-6 concentrations increased following ALX-0061 administration, with a dose-related increase in the duration of the effect, similar between the different administration routes. In addition, single iv and sc doses of ALX-0061 were safe and well tolerated at all doses tested in healthy volunteers. No deaths, severe adverse events or adverse events leading to discontinuation of dosing or subjects occurred. No clinically significant laboratory abnormalities, including irregularities in neutrophils and liver enzymes, were observed, for either of the administration routes. Ablynx intends to start the next Phase II studies with this subcutaneous formulation in RA in early 2015 and in SLE by mid-2015, with results from the RA studies expected in the second half of 2016.
• •  On April  23, 2014, Ablynx has announced that it has started dose administration in healthy volunteers in a Phase I clinical trial as part of the evaluation of a subcutaneous formulation of its anti-IL-6R Nanobody®, ALX-0061, for the treatment of inflammatory diseases, including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Results of the study are anticipated by the end of 2014, with the goal to start Phase II clinical development of ALX-0061 sc in both RA and SLE patients in 2015.
• In September 2013, Ablynx and AbbVie entered into a global license agreement, worth up to $840 million plus double-digit royalties, to develop and commercialise ALX-0061. As part of the agreement, Ablynx is responsible for the Phase I bioavailability study with the subcutaneous formulation of ALX-0061 and Phase II clinical development of ALX-0061 sc in RA and SLE, both of which are expected to start in 2015. Upon the achievement of pre-defined Phase II success criteria, AbbVie will exercise its right to in-license ALX-0061 and be responsible for subsequent Phase III clinical development and commercialisation.

 

Is general: Yes