Company: Ablynx (Belgium) AbbVie (USA -IL)
Product: ALX-0061 - vobarilizumab
- 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 been developed for the treatment of RA and possibly systemic lupus erythematosus (SLE). IL-6 is a pro-inflammatory cytokine that plays a role in T-cell activation, production of acute phase proteins in response to inflammation, induction of immunoglobulin production, and stimulation of osteoclast differentiation and activation. ALX-0061 (26kD) has a very strong affinity for the soluble IL-6R and contains an anti-IL-6R Nanobody linked to an anti-human serum albumin (HSA) Nanobody, thereby increasing the in vivo serum half-life. Phase I/II proof-of-concept results with ALX-0061 were published in February 2013, followed by the signing of a global exclusive licensing deal with AbbVie in September 2013 for the development and commercialisation of ALX-0061.
Disease: systemic lupus erythematosus (SLE)
area: Autoimmune diseases
- This Phase II STEADY study in SLE is a multi-centre, randomized, double-blind, placebo-controlled, dose-range finding study. It is expected to enrol approximately 300 subjects in the United States, Europe, South America and Asia, who will be randomly assigned to placebo or one of the four different dose groups of ALX-0061. Subjects will be followed for efficacy up to and including week 48 and for safety up to and including week 58.
- The study's primary endpoint is the percentage of subjects who achieved a response at week 24 according to the composite BICLA score (BILAG-based Combined Lupus Assessment). This is a broadly accepted, sensitive, clinically meaningful composite measure of SLE disease activity that requires disease improvement across all body systems with moderate or severe baseline activity without concurrent worsening in other body systems or increase in background medication. The secondary endpoints include the composite systemic lupus erythematosus responder index (SRI), the individual components of the composite endpoints, as well the effects of ALX-0061 on health-related quality of life, flare rate and use of corticosteroids. Other planned assessments include the determination of ALX-0061 levels, biomarkers, safety, tolerability and immunogenicity. (NCT02437890)
- • On March 26, 2018, Ablynx announced that the Phase II dose-ranging study of vobarilizumab did not meet the primary endpoint of dose response based on the modified BILAG-based combined lupus assessment (mBICLA) at Week 24. The study enrolled 312 patients with moderate to severe, active seropositive systemic lupus erythematosus across five treatment arms (four dose regimens of vobarilizumab and placebo). Demographics and baseline characteristics were similar across treatment arms, and reflective of a typical SLE population.
- Safety findings through Week 58 were favourable for vobarilizumab. Treatment-related serious adverse events were reported in 2.0% of all vobarilizumab treated patients compared to 6.5% in the placebo group. The percentage of patients experiencing a serious infection was also lower in the vobarilizumab arms compared to the placebo arm (2.8% versus 6.5%). Treatment-emergent adverse events that led to study drug discontinuation were reported in 12.4% of all vobarilizumab treated patients compared to 6.5% in the placebo group. Two deaths were reported in the vobarilizumab group.
- • On August 4, 2015, Ablynx announced that it has administered the first dose in the Phase II STEADY study to evaluate the efficacy and safety of its anti-IL-6R Nanobody®, ALX-0061, administered subcutaneously in adult patients with moderate to severe, active seropositive SLE, despite receiving the standard-of-care. The study also aims to identify the optimum dose and frequency of administration of ALX-0061 for the next phases of development