
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 |
Filed | |||
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 & clinicaltrials.gov. |