Amylyx’s chances rest on a knife edge

Negative, but not as negative as many had been expecting; this was the conclusion from yesterday’s adcom discussing Amylyx’s amyotrophic lateral sclerosis project AMX0035. Panellists voted 6-4 that efficacy had not been established, something that would normally point to an FDA rejection. However, after the controversial approval of another CNS drug, Biogen’s Aduhelm, also following a negative panel vote, the outcome for AMX0035 is anybody’s guess. Perhaps the FDA will be swayed by yesterday’s patient testimonies, and advocacy groups will no doubt keep up the pressure to approve AMX0035. It is also noteworthy that, amid questions about the statistical rigour of Amylyx’s phase 2 Centaur study, one vote in favour of the project came from the panel’s biostatistician, Dean Follmann. Evercore ISI’s Umer Raffat raised the possibility of accelerated approval, which was not discussed at yesterday’s adcom. While there is a lack of surrogate endpoints in ALS, Amylyx's phase 3 trial, Phoenix, is already under way – perhaps opening the door for a conditional approval with later confirmation if the trial is positive. Whichever way the FDA comes down, one thing is certain: Amylyx investors face a nervous wait before AMX0035’s June 29 Pdufa date.

Selected late-stage ALS projects 
Project Mechanism Company Status
MT-1186 (oral edaravone) Free-radical scavenger (same active ingredient as IV Radicava) Mitsubishi Tanabe Pdufa May 12, 2022
AMX0035 (sodium phenylbutyrate + Taurursodiol) Histone deacetylase inhibitor + bax inhibitor Amylyx Pdufa Jun 29, 2022; ph3 Phoenix completes Nov 2023
Phase 3
Masican (masitinib) CD117, FGFR3 & PDGFR antagonist AB Science AB19001 ends Dec 2023
Reldesemtiv  Troponin activator Cytokinetics Courage-ALS ends Dec 2023; project previously failed in ALS
Jacifusen (ION363) Fused in sarcoma antisense Ionis NCT04768972 ends Mar 2024
Tofersen Sod1 antisense oligo Biogen/Ionis Valor in symptomatic pts failed Oct 2021; Atlas in presymptomatic pts ends Aug 2026
Phase 2/3
Pridopidine Sigma-1 receptor agonist Prilenia Healey ALS Platform Trial – Regimen D* completes Mar 2022
Verdiperstat Myeloperoxidase enzyme inhibitor Biohaven Healey ALS Platform Trial – Regimen B* completes Apr 2022
CNM-Au8 Elemental gold nanocrystals Clene Nanomedicine Failed ph2 Rescue-ALS; Healey ALS Platform Trial – Regimen C* completes Apr 2022
Zilucoplan Complement factor C5 inhibitor UCB Healey ALS Platform Trial – Regimen A* completes Jun 2022
SLS-005 (IV trehalose) Natural disaccharide Seelos Therapeutics Healey ALS Platform Trial – Regimen E* completes Apr 2023
MN-166 (ibudilast/Ketas) Phosphodiesterase inhibitor Medicinova Combat-ALS completes Dec 2023
*Investigator-sponsored study. Source: Evaluate Pharma &

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