Low-dose solanezumab was found to slow clinical progression in Alzheimer disease with mild dementia, according to the results of a post hoc analysis published in the journal Alzheimer’s & Dementia.
Solanezumab is a monoclonal antibody that binds amyloid beta and prevents downstream fibrillar amyloid plaque formation.
To test whether solanezumab may have clinical utility in Alzheimer disease, researchers from Eli Lilly and Company conducted the multicenter, phase 3 EXPEDITION (ClinicalTrials.gov Identifier: NCT00905372v), EXPEDITION 2 (ClinicalTrials.gov Identifier: NCT00904683), and EXPEDITION 3 (ClinicalTrials.gov Identifier: NCT01900665) trials.
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In all trials, patients who had Alzheimer disease with mild to moderate dementia were randomly assigned to receive solanezumab 400 mg or placebo administered by intravenous infusion every 4 weeks through week 76. In this post hoc and meta-analysis, cognitive outcomes were evaluated among the subset of patients (N=3,437) who were aged 55 years and older and had Alzheimer disease with mild dementia, defined as a Mini-Mental State Examination (MMSE) score of 20 tp 26.
The mean age of patients in the pooled sample was 73.2 (SD, 7.94) years; 56.2% were women; 87.2% were White; 63.9% were apolipoprotein E (APOE) e4 carriers; and symptom onset was approximately 4.3 (SD, 2.54) years prior.
Compared with placebo (n=1720), those who received solanezumab (n=1700) had significantly better:
- Alzheimer’s Disease Assessment Scale–Cognitive subscale (ADAS-Cog) scores starting at week 28 (P <.05),
- Integrated Alzheimer’s Disease Rating Scale (iADRS) scores at week 28 (P <.05),
- Alzheimer’s Disease Cooperative Study–Activities of Daily Living Inventory (ADCS-ADL) scores at week 40 (P <.05), and
- MMSE scores at week 52 (P <.05).
For all outcomes, significant improvements with solanezumab compared with placebo were maintained through week 80 (all P £.01). In addition, sum boxes of the Clinical Dementia Rating Scale (CDR-SB) scores at week 80 were significantly improved with solanezumab compared with placebo (P <.05).
Overall, compared with placebo, the differences in scores indicated that solanezumab was associated with the following:
- 21% slowing in MMSE score decline,
- 20% slowing in ADCS-basic activities of daily living score,
- 18% slowing in ADAS-Cog score,
- 16% slowing in ADCS-ADL and iADRS scores,
- 15% slowing in ADCS-instrumental activities of daily living score, and
- 14% slowing in CDR-SB score decline.
The major limitation of this analysis was the lack of statistical significant of the primary outcomes of the individual studies.
This post hoc and meta-analysis found that solanezumab may have clinical utility in patients with Alzheimer disease with mild dementia.
“While the clinical meaningfulness of the effect of low-dose solanezumab in AD with mild dementia is uncertain, it is hypothesized that targeting patients earlier in the disease course or increasing the dose of solanezumab could have greater impact,” the researchers concluded. “[D]espite not meeting primary outcomes in completed phase 3 studies, low-dose solanezumab appears to have some clinical benefit and may demonstrate an effect that is worthy of clinical use at a higher dose and/or in earlier disease stages.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Reference
Holdridge KC, Yaari R, Hoban DB, Andersen S, Sims JR. Targeting amyloid β in Alzheimer’s disease: meta-analysis of low-dose solanezumab in Alzheimer’s disease with mild dementia studies. Alzheimers Dement. Published online March, 22, 2023. doi:10.1002/alz.13031
This article originally appeared on Neurology Advisor
