Solanezumab Extension Study Offers Basis for Continued Study in Early Alzheimer’s
In a 3.5-year extension study, Lilly’s anti-amyloid mAb solanezumab (sola, for short) continued to provide statistically significant cognitive benefits to those patients with mild AD who were originally treated with the drug (in the double-blind phase of the trial). The results, in detail, were reported today at the ongoing AAIC in Washington, DC, and picked up by numerous media outlets.
The quickest read of the results can be found here (thanks, Fierce Biotech). Statistically significant, but very marginal, differences were seen between patients originally treated with sola and those originally given placebo in the areas of cognition (ADAS-cog14) and instrumental activities of daily living (ADCS-iADL).* No effect, however, was detected in global function (CDR-SB) or the MMSE. The data suggest that, while sola may provide some measurably small benefit in mild AD, the effects are far from clinically profound. Perhaps, they’re not even clinically meaningful.
Lilly says that the extension trial, although not blinded, is akin to a delayed-start trial,** which can be used in an attempt to show a disease-modifying (as opposed to a merely symptomatic) effect of an active compound. The company is making much of the fact that the originally placebo-treated patients did not “catch up” to the comparator group, suggesting a disease-modifying effect for sola. That’s possible; although the statistical margin between the two treatment groups is uncomfortably narrow. The curves, while parallel, are very close to being superimposable.
Notably Lilly is conducting a trial of sola in older individuals who show evidence of amyloid build-up in their brains but do not exhibit clinically apparent AD (MMSE scores, 25-30).
* It’s not clear to this writer if sola had an effect on basic ADLs in the extension study. I suspect not, if the result wasn’t trumpeted by Lilly.
** Although isn’t every open-label extension trial a delayed-start trial, if using Lilly’s definition?
AAIC = Alzheimer’s Association International Conference; AD = Alzheimer disease; ADAS-cog14 = 14-item cognitive subscale of the Alzheimer’s Disease Assessment Scale; ADCS-iADL = Alzheimer’s Disease Cooperative Study, Activities of Daily Living, instrumental subscale; CDR-SB = Clinical Dementia Rating scale, Sum of Boxes; mAb = monoclonal antibody; MMSE = Mini-Mental State Examination.
Above: Pittsburgh Compound B (PiB) PET scan showing amyloid buildup in the brain.
A native East Tennessean, Barbara Martin is a formerly practicing, board-certified neurologist who received her BS (psychology, summa cum laude) and MD from Duke University before completing her postgraduate training (internship, residency, fellowship) at the Hospital of the University of Pennsylvania in Philadelphia. She has worked in academia, private practice, medical publishing, drug market research, and continuing medical education (CME). For the last 3 years, she has worked in a freelance capacity as a medical writer, analyst, and consultant. Follow Dr. Barbara Martin on Google + and Twitter.
