Biogen and Ionis stumble again

Chalk up yet another disappointment in amyotrophic lateral sclerosis, and another for Ionis and Biogen. Today the partners said they were discontinuing BIIB078 after it failed to show a clinical benefit in a phase 1 trial. There is not much to go on, but worryingly patients receiving a high dose, 90mg, had worsening disease versus placebo; those on 60mg showed no benefit. Stifel analysts reckon this suggests dose-dependent toxicity, which could spell trouble for Ionis’s antisense approach – especially after its Roche-partnered Huntington’s project tominersen was linked with a similar phenomenon. And Biogen is particularly exposed to this technology, having paired up with Ionis on various CNS antisense projects. The Sod1 antisense tofersen is still in play in presymptomatic ALS, but its future looks dim after the failure of the Valor trial last year. While BIIB078 and tofersen were designed for specific genetic subtypes of ALS, the partners also have a potentially universal therapy, BIIB105, in development; and Ionis has a wholly owned phase 3 asset, jacifusen (ION363), for ALS with mutations in the FUS gene. Still, data on the latter are some way off. More immediately, an adcom this week will discuss the approval chances of Amylyx’s AMX0035.

Biogen/Ionis partnered projects
Project Indication Description Status
Tofersen (BIIB067) Sod1-associated ALS Sod1 antisense Failed ph3 Valor in symptomatic pts; Atlas in presymptomatic subjects ends Aug 2026
BIIB078 (IONIS-C9Rx) C9orf72-associated ALS C9orf72 antisense Failed ph1; project discontinued
BIIB080 (IONIS-MAPTRx) Alzheimer's Tau antisense Ph1/2 completes May 2022
BIIB101 (ION464) Parkinson's & MSA Alpha-synuclein antisense Ph1 Horizon completes Jul 2022
ION582  Angelman syndrome UBE3A-ATS antisense Ph1/2 Halos completes Jul 2023
BIIB094 (ION859) Parkinson's LRRK2 antisense Ph1 Reason completes Sep 2023
BIIB105 (ION541) ALS Ataxin 2 antisense Ph1 completes Dec 2024 
MSA=multiple system atrophy. Source: Ionis website, Evaluate Pharma &

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