Solanezumab failed to significantly affect cognitive decline among patients with mild Alzheimer’s disease, according to study findings published in NEJM.
“This study of an antibody to soluble beta-amyloid did not show a statistically significant effect on the primary measure, but changes in that measure, as well as in nearly all of the secondary measures, showed a small benefit of the drug; and there were no safety concerns,” Lawrence S. Honig, MD, PhD, Columbia University Medical Center, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, told Healio Psychiatry.
Researchers conducted a double-blind, placebo-controlled phase 3 trial to determine the effectiveness of solanezumab — an antibody designed to increase the clearance from the brain of soluble amyloid-beta — for Alzheimer’s disease. In the trial, the investigators randomly assigned patients with mild dementia due to Alzheimer’s disease and with amyloid deposition to receive solanezumab at a dose of 400 mg or placebo via IV every 4 weeks for 76 weeks. They assessed change from baseline to week 80 in the Mini-Mental State Examination (MMSE) score on the 14-item cognitive subscale of the Alzheimer’s Disease Assessment Scale.
Of 2,129 patients enrolled in the trial, 1,057 received solanezumab and 1,072 received placebo. The mean change from baseline in the cognition score was 6.65 for solanezumab and 7.44 for placebo, with no significant difference at week 80 between the groups (difference, –0.80; 95% CI, –1.73 to 0.14). In the secondary analyses, the researchers observed that the treatment effect in this study showed a smaller rate of cognitive decline compared to two previous phase 3 studies that assessed the effectiveness of solanezumab in patients with mild Alzheimer’s disease. Analysis of secondary outcomes showed worsening MMSE scores; change from baseline in the MMSE score was –3.17 in the solanezumab group and –3.66 in the placebo group. Notable adverse events occurred in one patient in the solanezumab group and two in the placebo group, indicating no significant differences between the groups.
“While the possible small benefit is not definitive, and it is possible that this drug is not the right class of drug, it is also quite possible that this drug was just not delivered in high enough dosage, or possibly not delivered early enough in the disease process,” Honig said. “It would appear that we are slowly getting closer and closer to the development of an efficacious drug to slow the progression of Alzheimer’s disease.” – by Savannah Demko
Disclosures: Honig reports grant support and consulting fees from Bristol-Myers Squibb, Eisai, Forum Pharmaceuticals and Lundbeck; grants and travel support from Eli Lilly and consulting fees from Fujirebio; grants from AbbVie, AstraZeneca, Axovant, Biogen, C2N Diagnostics, Genentech, Janssen–Johnson & Johnson, Merck, Pfizer, Roche, TauRx and vTv Therapeutics.