Move over Aduhelm, it’s tofersen’s turn

Biogen has clearly not been deterred by the Aduhelm debacle, today shooting for another accelerated approval on the basis of a questionable biomarker. This time the project is the Ionis-partnered tofersen in Sod1-mutated amyotrophic lateral sclerosis, and the biomarker is neurofilament light chain. NfL has been shown to increase with neuronal damage, raising hopes that it could be used to track the progression of various neurological diseases. However, results have not always been consistent: Denali, for example, found an increase in NfL with its Hunter syndrome project DNL310, alongside promising clinical data. Biogen and Ionis, meanwhile, found no clinical benefit with tofersen in the pivotal Valor trial – but they did report a reduction in NfL. Stifel analysts believe that the tofersen data “further complicate the picture around neurofilament's utility”, but expect Biogen to argue that there could be a time lag between NfL and clinical efficacy. This will likely be fiercely debated at an adcom before tofersen’s January 25 Pdufa date. Another ALS adcom is also approaching, with Amylyx’s AMX0035 set to face a panel for the second time in September; that project initially received a 6-4 vote against approval.

Selected late-stage ALS projects 
Project Mechanism Company Status
AMX0035 (sodium phenylbutyrate + taurursodiol) Histone deacetylase inhibitor + bax inhibitor Amylyx Pdufa Sep 29 (extended by 3mth); 2nd adcom Sep 7; approved in Canada Jun 2022; ph3 Phoenix completes Nov 2023
Tofersen Sod1 antisense oligo Biogen/Ionis Pdufa Jan 25, 2023; adcom expected (date TBC); Valor in symptomatic pts failed Oct 2021; Atlas in presymptomatic pts ends Aug 2026
Phase 3
Masican (masitinib) CD117, FGFR3 & PDGFR antagonist AB Science AB19001 ends Dec 2023
Reldesemtiv  Troponin activator Cytokinetics Courage-ALS ends Dec 2023, first interim analysis due H2 2022; project previously failed in ALS
Jacifusen (ION363) Fused in sarcoma antisense Ionis NCT04768972 ends Mar 2024
Phase 2/3
Zilucoplan Complement factor C5 inhibitor UCB Healey ALS Platform Trial – Regimen A* completed Apr 2022
Verdiperstat Myeloperoxidase enzyme inhibitor Biohaven Healey ALS Platform Trial – Regimen B*, data due H2 2022
CNM-Au8 Elemental gold nanocrystals Clene Nanomedicine Failed ph2 Rescue-ALS; Healey ALS Platform Trial – Regimen C* data due Q3 2022
Pridopidine Sigma-1 receptor agonist Prilenia Healey ALS Platform Trial – Regimen D*, data due "late 2022"
SLS-005 (IV trehalose) Natural disaccharide Seelos Therapeutics

Healey ALS Platform Trial – Regimen E*, data due mid-2023

MN-166 (ibudilast/Ketas) Phosphodiesterase inhibitor Medicinova Combat-ALS completes Dec 2023
*Investigator-sponsored study. Source: Evaluate Pharma &

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