Biogen and partner Eisai said early Thursday that they are terminating their global phase III trials of aducanumab, a monoclonal antibody targeting beta-amyloid protein in Alzheimer’s disease, after interim analyses indicated that the agent was ineffective.
“The decision to stop the trials is based on results of a futility analysis conducted by an independent data monitoring committee, which indicated the trials were unlikely to meet their primary endpoint upon completion. The recommendation to stop the studies was not based on safety concerns,” the firms said in a press release.
Aducanumab may not be entirely dead, however, as Biogen and Eisai said a planned phase III trial for “secondary prevention” might still get underway, pending further evaluation of the now-ended studies called ENGAGE and EMERGE.
Both of the latter were conducted in patients with “early” Alzheimer’s disease, defined as mild Alzheimer’s or mild cognitive impairment due to Alzheimer’s disease. Specific inclusion criteria were Mini-Mental State Examination (MMSE) scores of 24-30 and a Clinical Dementia Rating (CDR) global score of 0.5.
In both studies, which were placebo-controlled, the primary endpoint was change in baseline in CDR-Sum of Boxes at week 78; the futility analysis determined that aducanumab was unlikely to outperform sham infusions upon final completion.
Aducanumab came to prominence in 2015, when a 188-patient phase Ib study delivered a stunning result: patients not only showed decreases in amyloid plaque burdens, but also clearly slower cognitive decline. On the strength of those data, Biogen elected not to wait for phase II results but to go instead straight into phase III. EMERGE and ENGAGE aimed to enroll more than 3,200 patients in total.
Investors were apparently optimistic about how they would go: Biogen’s stock dropped 30% within minutes of Thursday’s announcement.
With hopes for aducanumab now dangling by a thread, the field’s attention is likely to shift in two directions: toward the only other anti-amyloid agent still in advanced testing, Eli Lilly’s solanezumab; and away from amyloid altogether as a treatment target. Notably, the Biogen/Eisai announcement came the same day that an FDA advisory committee is considering a magnetic stimulation device for treating Alzheimer’s patients.
Although solanezumab already failed in a phase III trial — involving patients with mild disease — many in the field still think it could deliver a win in the so-called A4 trial, which is targeting individuals with so-called preclinical Alzheimer’s disease. Lilly is doing everything it can to maintain the excitement, going so far as to underwrite a documentary focusing on solanezumab called “The Turning Point,” showing at film festivals and other select venues. Primary results from A4 are expected in 2022.