Low-Dose Solanezumab May Help Slow Cognitive Decline in AD With Mild Dementia

Low-dose solanezumab was found to slow clinical progression in Alzheimer disease (AD) with mild dementia, according to the results of a post hoc analysis published in the journal Alzheimer’s & Dementia.

Solanezumab is a monoclonal antibody which binds amyloid b (Ab) and prevents downstream fibrillar amyloid plaque formation.

To test whether solanezumab may have clinical utility in AD, researchers from Eli Lilly and Company conducted the EXPEDITION (ClinicalTrials.gov Identifier: NCT00905372v), EXPEDITION 2 (ClinicalTrials.gov Identifier: NCT00904683), and EXPEDITION 3 (ClinicalTrials.gov Identifier: NCT01900665) trials, which were multicenter, phase 3 trials.

In all trials, patients who had AD with mild to moderate dementia were randomly assigned to receive 400 mg solanezumab 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 or older and had AD with mild dementia, defined as Mini-Mental State Examination (MMSE) score of 20-26.

The pooled sample comprised of patients mean age, 73.2 (SD, 7.94) years; 56.2% were women; 87.2% were White; 63.9% were apolipoprotein E (APOE) e4 carriers; and their symptoms had onset 4.3 (SD, 2.54) years prior.

Compared with placebo (n=1,720), those who received solanezumab (n=1,700) 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 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 compared with control individuals (P <.05).

Overall, compared with placebo, the differences in scores indicated solanezumab associated with a:

• 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 fact that the primary outcomes of the individual studies did not reach statistical significance.

This post hoc and meta-analysis found that solanezumab may have clinical utility in AD 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.