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Semorinemab Pharmacokinetics and The Effect on Plasma Total Tau Pharmacodynamics in Clinical Studies
V Ramakrishnan, B Bender, J Langenhorst, M O Magnusson, M Dolton, J Shim, R N Fuji, C Monteiro et al.. The journal of prevention of Alzheimer's disease, 2024
Topic: Drug trials: efficacy and safety
Serum concentrations of semorinemab were consistent across studies and showed a dose-proportional increase across the evaluated dose range. The pharmacokinetic profile was comparable between healthy volunteers and subjects with Alzheimer's disease. Total plasma tau concentrations increased in a dose-dependent non-linear manner upon semorinemab administration. The target-mediated drug disposition model adequately described the serum pharmacokinetics and protein dynamics with an estimated antibody-ligand binding strength, Kss, of 42.7 nM. The estimated values of clearance and central volume of distribution were 0.109 L/day/70 kg and 2.95 L/70 kg, respectively, and were consistent with typical values for IgG mAbs. In the sensitivity analysis, Kss (32 nM) and baseline tau protein (0.30 µM) were estimated to be lower for healthy volunteers compared to subjects with Alzheimer's disease but were comparable between subjects with Alzheimer's disease of different severities (Kss: 52-57 nM, baseline tau: 0.44-0.47 µM). The models suggested that peripheral target engagement was over 90% at the clinical doses in each of the diagnostic subgroups. Our target-mediated drug disposition model adequately described the serum pharmacokinetics and the peripheral non-linear increase with dose of the total tau. The model confirmed that these dose-response relationships were consistent across populations of healthy volunteers and subjects with different severities of Alzheimer's disease.
Key findings
- Serum concentrations of semorinemab were consistent across studies and showed a dose-proportional increase across the evaluated dose range.
- The pharmacokinetic profile was comparable between healthy volunteers and subjects with Alzheimer's disease.
- Total plasma tau concentrations increased in a dose-dependent non-linear manner upon semorinemab administration.
- The target-mediated drug disposition model adequately described the serum pharmacokinetics and protein dynamics with an estimated antibody-ligand binding strength, Kss, of 42.7 nM.
- The estimated values of clearance and central volume of distribution were 0.109 L/day/70 kg and 2.95 L/70 kg, respectively, and were consistent with typical values for IgG mAbs.
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Study details
- Study designclinical trial
- Participants8,430
- Evidence strengthLow
How this study scored 54/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 30 of the 56 points we could judge it on, which is 54 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The journal of prevention of Alzheimer's disease) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | Design recorded as “clinical trial”, which our rubric does not rank (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 3 / 4 | 8,430 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39350369) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 30 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 30 of the 56 points we could judge it on is 54 out of 100. |
| Total | 54 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Ramakrishnan, V., Bender, B., Langenhorst, J., Magnusson, M. O., Dolton, M., Shim, J., et al. (2024). Semorinemab Pharmacokinetics and The Effect on Plasma Total Tau Pharmacodynamics in Clinical Studies. The journal of prevention of Alzheimer's disease. https://doi.org/10.14283/jpad.2024.146
Vancouver
Ramakrishnan V, Bender B, Langenhorst J, Magnusson MO, Dolton M, Shim J, et al. Semorinemab Pharmacokinetics and The Effect on Plasma Total Tau Pharmacodynamics in Clinical Studies. The journal of prevention of Alzheimer's disease. 2024. doi:10.14283/jpad.2024.146. PMID: 39350369.
BibTeX
@article{ramakrishnan2024-39350369,
author = {Ramakrishnan, V and Bender, B and Langenhorst, J and Magnusson, M O and Dolton, M and Shim, J and Fuji, R N and Monteiro, C and others},
title = {{Semorinemab Pharmacokinetics and The Effect on Plasma Total Tau Pharmacodynamics in Clinical Studies}},
journal = {The journal of prevention of Alzheimer's disease},
year = {2024},
doi = {10.14283/jpad.2024.146},
pmid = {39350369},
url = {https://doi.org/10.14283/jpad.2024.146}
}
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