Donanemab rejection throws Lilly a new curveball

A US complete response letter for Lilly’s Alzheimer’s hope donanemab was always possible, given that the project has yet to generate phase 3 data, though the apparent reason behind it comes as a surprise. Lilly has claimed that the CRL cites just one deficiency: its accelerated approval filing does not include enough patients with at least 12 months’ exposure to donanemab. Guidelines require the safety database to comprise at least 100 patients exposed for a minimum of one year. Crucially, Lilly stops dosing donanemab once patients’ plaque clears; though in the phase 2 Trailblazer-Alz trial 131 patients got donanemab, because of “the speed of plaque reduction many were able to stop dosing as early as 6 months”, Lilly says – a claim supported by donanemab’s mechanistic efficiency. The CRL throws attention forward to the phase 3 Trailblazer-Alz 2 study readout, which should come in the second quarter and could back full approval; most had always viewed this as donanemab’s real catalyst. Lilly must hope for sufficient patient exposures in the combined datasets, and will face another issue: Leqembi, whose confirmatory Clarity-AD study Eisai had filed the same day it got accelerated approval, might soon boast full approval of its own.

A recent Alzheimer's timeline
Jul 2021 Biogen/Eisai's Aduhelm receives US accelerated approval
Jan 2022 US CMS effectively refuses to reimburse Aduhelm
Nov 2022 Roche's gantenerumab fails in phase 3
6 Jan 2023 Eisai/Biogen's Leqembi receives US accelerated approval
6 Jan 2023 Eisai files Clarity-AD data, seeking full US Leqembi approval
19 Jan 2023 US complete response letter for Lilly's donanemab
Due Q2 2023 Readout of donanemab's confirmatory Trailblazer-Alz 2 study
Due 2023 Full US approval of Leqembi

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