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Attention Score in Context
| Title |
The preclinical pharmacology of the high affinity anti-IL-6R Nanobody® ALX-0061 supports its clinical development in rheumatoid arthritis
|
|---|---|
| Published in |
Arthritis Research & Therapy, May 2015
|
| DOI | 10.1186/s13075-015-0651-0 |
| Pubmed ID | |
| Authors |
Maarten Van Roy, Cedric Ververken, Els Beirnaert, Sven Hoefman, Joost Kolkman, Michel Vierboom, Elia Breedveld, Bert ‘t Hart, Sofie Poelmans, Lieselot Bontinck, Alex Hemeryck, Sandy Jacobs, Judith Baumeister, Hans Ulrichts |
| Abstract |
The pleiotropic cytokine interleukin-6 (IL-6) plays an important role in the pathogenesis of different diseases, including rheumatoid arthritis (RA). ALX-0061 is a bispecific Nanobody with a high affinity and potency for IL-6 receptor (IL-6R), combined with an extended half-life by targeting human serum albumin. We describe here relevant aspects of its in vitro and in vivo pharmacology. ALX-0061 is composed of an affinity-matured IL-6R-targeting domain fused to an albumin-binding domain representing a minimized two-domain structure. A panel of different in vitro assays was used to characterize the biological activities of ALX-0061. The pharmacological properties of ALX-0061 were examined in cynomolgus monkeys using plasma levels of total soluble (s)IL-6R as pharmacodynamic marker. Therapeutic effect was evaluated in a human IL-6-induced acute phase response model in the same species and in a collagen-induced arthritis (CIA) model in rhesus monkey, using tocilizumab as positive control. ALX-0061 was designed to confer the desired pharmacological properties. A 200-fold increase of target affinity was obtained through affinity maturation of the parental domain. The high affinity for sIL-6R (0.19 pM) translated to a concentration-dependent and complete neutralization of sIL-6R in vitro. In cynomolgus monkey, ALX-0061 showed a dose-dependent and complete inhibition of hIL-6-induced inflammatory parameters, including plasma levels of C-reactive protein (CRP), fibrinogen and platelets. An apparent plasma half-life of 6.6 days was observed after single intravenous administration of 10 mg/kg ALX-0061 in cynomolgus monkey, similar to the estimated expected half-life of serum albumin. ALX-0061 and tocilizumab demonstrated a marked decrease in serum CRP levels in a non-human primate CIA model. Clinical effect was confirmed in animals with active drug exposure throughout the course of the study. ALX-0061 represents a minimized bispecific biotherapeutic of 26 kDa, nearly 6 times smaller than monoclonal antibodies. High in vitro affinity and potency was demonstrated. Albumin binding as a half-life extension technology resulted in describable and expected pharmacokinetics. Strong IL-6R engagement was shown to translate to in vivo effect in non-human primates, demonstrated via biomarker deregulation as well as clinical effect. Presented results on preclinical pharmacological properties of ALX-0061 are supportive of clinical development in RA. |
Mendeley readers
The data shown below were compiled from readership statistics for 204 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | <1% |
| Germany | 1 | <1% |
| Brazil | 1 | <1% |
| Unknown | 201 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 40 | 20% |
| Student > Master | 31 | 15% |
| Researcher | 26 | 13% |
| Student > Bachelor | 19 | 9% |
| Other | 14 | 7% |
| Other | 25 | 12% |
| Unknown | 49 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 51 | 25% |
| Agricultural and Biological Sciences | 32 | 16% |
| Pharmacology, Toxicology and Pharmaceutical Science | 18 | 9% |
| Medicine and Dentistry | 15 | 7% |
| Immunology and Microbiology | 12 | 6% |
| Other | 25 | 12% |
| Unknown | 51 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 October 2022.
All research outputs
#3,799,086
of 25,374,917 outputs
Outputs from Arthritis Research & Therapy
#902
of 3,380 outputs
Outputs of similar age
#47,609
of 280,290 outputs
Outputs of similar age from Arthritis Research & Therapy
#19
of 63 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. Compared to these this one has done well and is in the 83rd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,380 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one has gotten more attention than average, scoring higher than 72% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 280,290 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 82% of its contemporaries.
We're also able to compare this research output to 63 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 69% of its contemporaries.