Arimoclomol failure leaves Biogen/Ionis exposed

Snippets

Biogen is under increasing pressure – as if it needs it – to deliver with its Ionis-partnered mRNA project tofersen in amyotrophic lateral sclerosis. The asset looks increasingly exposed among pivotal-stage ALS projects after the recent failure of Brainstorm’s NurOwn and that of Orphazyme’s arimoclomol, announced this morning. Investors will have to wait another week to find out the data from arimoclomol’s pivotal ALS trial, Orarials-01, when these are presented at the Encals meeting; for now, Orphazyme says in the 245-patient study arimoclomol failed to beat placebo on either its primary measure, 76-week CAFS score, or secondary endpoints, which included the ALSFRS-R score and slow vital capacity. This comes after US FDA said Brainstorm’s unequivocally negative pivotal study of the stem cell therapy NurOwn was insufficient for filing, Orion’s levosimendan failed in the Refals trial, and Amylyx was told that it had to run a full phase 3 study with AMX0035. Tofersen’s phase 3 Valor study, ending mid-2021, is the next big readout for ALS. In addition to failing in ALS arimoclomol has also flunked trials in inclusion body myositis and Niemann-Pick disease, though Orphazyme is pursuing a filing in the last indication.

Late-stage ALS pipeline (selected projects, excluding riluzole formulations)
Project Mechanism Company Trial Note
Phase III
Simdax po (levosimendan) PDE3 inhibitor Orion NCT03505021 (Refals) Failed Jul 2020
NurOwn Program One Cell therapy Brainstorm Cell Therapeutics NCT03280056 Failed Nov 2020; data insufficient for filing
Arimoclomol citrate SOD1 chaperone Orphazyme (ex Cytrx) NCT03491462 (Orarials-01) Failed May 2021
Tofersen SOD1 inhibitor mRNA Biogen/Ionis NCT02623699 (Valor) 183 subjects; data due H2 2021
Ultomiris Anti-complement factor C5 Mab Alexion NCT04248465 382 subjects, ends Feb 2022
Alsitek (masitinib) CD117, FGFR3 & PDGFR antagonist AB Science NCT03127267 495 subjects, not yet recruiting, ends Dec 2022
Phase II/III
AMX0035 (sodium phenylbutyrate + Taurursodiol) Histone deacetylase inhibitor + bax inhibitor Amylyx NCT03127514 (Centaur) Centaur met primary endpoint, but FDA has demanded a full ph3 trial
CuATSM  Unknown Collaborative Medicinal Development NCT04082832 80 subjects; study ended, no data
Zilucoplan Complement factor C5 inhibitor UCB NCT04436497 (HEALEY ALS Platform Trial – Regimen A) 160 subjects, ends Oct (previously Mar) 2021
Verdiperstat Myeloperoxidase enzyme inhibitor Biohaven NCT04436510 (HEALEY ALS Platform Trial – Regimen B) 161 subjects, ends Oct (previously Mar) 2021
CNM-Au8 Elemental gold nanocrystals Clene Nanomedicine NCT04414345 (HEALEY ALS Platform Trial – Regimen C) 162 subjects, ends Oct (previously Mar) 2021
Ketas (ibudilast/MN-166) LTD4 receptor antagonist Medicinova NCT04057898 (Combat-ALS) 230 subjects, ends Dec 2023
Source: clinicaltrials & Evaluate Pharma.

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