Eisai and Biogen’s Alzheimer’s drug flunks early adaptive trial readout

Eisai and Biogen’s hopes of an early positive readout for anti-amyloid beta drug BAN2401 in Alzheimer’s disease (AD) have been dashed, but they’re not giving up on the program yet.

The adaptive phase 2 trial in patients with mild or prodromal AD included a 12-month data readout that the two partners hoped would give an early signal of efficacy for the drug. An independent data monitoring committee has just taken a look at those results and—disappointingly—it doesn’t look hopeful.

Eisai and Biogen said they will play the trial out to its pre-specified 18-month endpoint, and insist that the early readout doesn’t spell the end for BAN2401. Nevertheless, the miss adds to anxiety that BAN2401 may go the same way as the large number of other amyloid-targeted drug programs that have ended in failure, and Biogen’s share price was on the slide in after-hours trading.

The proof of concept study used the adaptive design to try to get a verdict on whether to proceed to phase 3 earlier—and more cheaply—than with typical phase 2 trial designs. It has been suggested that one of the reasons so many AD drugs fail in late-stage trials is that phase 2 trials have not been sufficiently robust. The final data on clinical endpoints from this trial should be ready in the second half of next year.

“By using Bayesian statistics in this uniquely-designed trial we had hoped that it would enable us to demonstrate clinical success faster than more traditional study designs,” commented Lynn Kramer, M.D., Eisai’s chief medical officer.

“We now await the final study analysis which will be conducted after 18 months of treatment, which represents an amount of treatment time that is considered as appropriate for assessing efficacy in disease modifying agents for Alzheimer’s disease.” The clinical endpoints will include cognitive and memory measures as well as biomarkers such as brain amyloid levels.

BAN2401 is one of the AD programs in Biogen and Eisai’s longstanding partnership along with BACE inhibitor elenbecestat (E2609), which moved into phase 3 last year, and aducanumab, which reported encouraging three-year data in a phase 1b study last month and is also in late-stage testing.