After first pledging to file aducanumab in early 2020 Biogen today revealed that it had only now submitted the controversial Alzheimer’s disease project to the US FDA, sending shares up 5%. The FDA now has 60 days to accept or reject the filing and decide whether to grant priority review. And here lies the rub: there are questions around Biogen’s data package, including missing data values and a less than convincing efficacy profile. An advisory committee will no doubt be called to scrutinise the toxicity profile and statistical rigour of aducanumab's clinical programme. However, given the paucity of Alzheimer’s treatments and an FDA that has shown leniency towards treatments for intractable diseases with no other options, aducanumab’s filing looks likely to be accepted. Beyond aducanumab Biogen’s pipeline is thin, and a patent loss for Tecfidera last month deepened the company’s reliance on the Alzheimer’s project. Roche and Lilly have both spent years trying to gain ground with their own beta amyloid-targeting MAbs, and will surely keep a close eye on the regulator’s proceedings.
Aducanumab's phase III dataset (high dose) | ||||
---|---|---|---|---|
Emerge | Engage | |||
n=547 | n=555 | |||
CDR-SB (original primary endpoint) | ||||
Reduction vs placebo | -22% | 2% | ||
Nominal p value | 0.01 | 0.833 | ||
Adas-Cog (one of 3 secondary endpoints) | ||||
Reduction vs placebo | -27% | -11% | ||
Nominal p value | 0.01 | 0.258 | ||
Source: 2019 CTAD presentation. |
Beta amyloid MAbs in late-stage development | ||||
---|---|---|---|---|
Project | Company | Indication sales 2026e ($m) | Disease setting | Note |
Phase III | ||||
Aducanumab | Biogen/Eisai | 2,894 | Early/mild | Completed FDA filing based on two phase III studies, Emerge and Engage, and phase Ib Prime |
BAN2401 (lecanemab) |
Biogen/Eisai | 969 | Early | Clarity AD study due to report in 2022 |
Gantenerumab | Roche | 69 | Early | Graduate 1 and 2 studies, primary completion 2022 |
Solanezumab | Lilly | - | Asymptomatic | A4 study, primary completion 2022 |
Phase II | ||||
LY3002813 (donanemab) |
Lilly | 22 | Early | Trailblazer-Alz, data due Jan 2021 |
Crenezumab | Roche/AC Immune | - | Autosomal dominant | NCT01998841, primary completion 2022 |
Source: EvaluatePharma, clinicaltrials.gov. |