Lilly’s Compound Shows Marginal Benefit in Mild Alzheimer Disease
Solanezumab, Lilly’s anti-amyloid MAb, may provide some clinical benefit in patients with mild AD, according to data presented yesterday by the AD Cooperative Study group. The independent group presented pooled data from Lilly’s 2 phase 3 studies (EXPEDITION 1 and 2) at the ANA meeting in Boston.
- In patients with mild AD from EXPEDITION 1, solanezumab slowed cognitive decline (via the ADAS-cog11) by a statistically significant 42% (P = .008). However, the absolute difference between solanezumab- and placebo-treated patients was not provided, nor was the rate of decline of placebo-treated patients provided in the press release. (There was no treatment-related difference in ADCS-ADL scores.)
- In patients with mild AD from EXPEDITION 2, solanezumab slowed cognitive decline (via the ADAS-cog14**) by 20%; however, this difference was not statistically significant (P = .008). (There was a statistical trend toward a treatment-related difference in the ADCS-ADL scores [P = .076].)
- In patients with mild AD from EXPEDITION 1 and 2 (pooled data), solanezumab slowed cognitive decline (via the ADAS-cog14) by a statistically significant 34% (P = .001). (And there was a statistical trend toward a treatment-related difference in the ADCS-ADL scores [P = .057].) However, according to MedPage Today, the absolute score difference on the ADAS-cog14 was only 1.3 points per year.
The possible clinical effects of solanezumab did not appear to be dependent on APOE ε4 genetic status. Also curious was the outcome that solanezumab affected only some AD biomarkers in these post-hoc study populations. (The biomarker data will apparently be presented at the CTAD meeting in Monte Carlo later this month.)
Angina (?) was statistically significantly more common in solanezumab-treated patients (1.1% vs 0.2% with placebo). Vasogenic edema (ie, ARIA-E) occurred in 11 solanezumab-treated patients (~1%) and 5 placebo-treated patients (no statistical difference).
A more thorough assessment of these data is needed, specifically in peer-reviewed form, before certain assumptions (or hopes) about solanezumab can be concluded. It’d be really nice to know the cognitive decline of the placebo-treated groups. What raised hopes about bapineuzumab, Pfizer/JNJ’s now-defunct anti-amyloid MAb, was the statistical difference between actively treated and placebo-treated groups in the phase 2 studies. However, the difference may have been artificial, because the placebo-treated patients declined at a more rapid rate than might be expected in AD.
Regardless of any reservations about solanezumab, Lilly’s share price shot up about 8% (from ~$48 to ~$52) on the promising news.
ADAS-cog = Alzheimer Disease Assessment Scale-cognitive subscale; ADCS-ADL = Alzheimer Disease Cooperative Study-activities of daily living; ANA = American Neurological Association; APOE ε4 = apolipoprotein E, ε4 allele; ARIA-E = amyloid-related imaging abnormalities-edema; CTAD = Clinical Trials on Alzheimer Disease; EXPEDITION = Effect of LY2062430, an Anti-Amyloid Beta Monoclonal Antibody, on the Progression of Alzheimer’s Disease as Compared With Placebo; MAb = monoclonal antibody.
* Unfortunately I can’t find the actual abstract (or any filmed presentation) at the ANA meeting website.
** Lilly changed the prespecified primary outcome from ADAS-cog11 to ADAS-cog14.