Biogen leads the amyotrophic lateral sclerosis hopefuls
Despite several recent late-stage failures, there is still a lot going on in the ALS pipeline.
Amylyx’s decision this week to pursue early US approval of its amyotrophic lateral sclerosis project AMX0035 put the focus back on a field that has seen more than its fair share of disappointment of late.
And, surprisingly, the mid-to-late-stage pipeline looks full, with many different approaches being tested. “I’ve been in the field for about nine years and, during that time, there’s never been as many trials and companies as there are today,” Amylyx’s co-chief executive officer, Josh Cohen, told Evaluate Vantage.
However, he added a note of caution: “I think it’s going to take a lot of shots on goal. We can’t expect every trial to succeed.”
Biogen and Ionis's push
The next attempt will involve Biogen and Ionis’s tofersen, which is being tested in Sod1-mutated ALS in the pivotal Valor trial, due to yield data this half. Biogen also has several other projects in phase 1: the anti-C9orf72 oligo BIIB078 and the anti-ataxin-2 oligo BIIB105, both also partnered with Ionis, and the exportin 1 inhibitor BIIB100, licensed from Karyopharm.
In addition, Ionis has a wholly owned candidate, ION363, which went into phase 3 this year.
Still, not all of the late-stage hopefuls are on solid ground. Cytokinetics has opted to take its contender reldesemtiv into pivotal development despite the failure of the phase 2 Fortitude trial. And that was after the company’s first-generation troponin activator, tirasemtiv, had already proven a dud.
If troponin activation is not the way to go there are still plenty of other mechanisms being tested, notably in the academia-led Healey-ALS platform trial. The first few arms, involving UCB’s zilucoplan, Biohaven’s verdiperstat and Clene Nanomedicine’s CNM-Au8, are set to complete soon.
This year the trial added Prilenia’s priodopidine, and Seelos Therapeutics’ SLS-005 has also been selected, with dosing set to begin this quarter, the company said during its second-quarter results.
Zilucoplan is not the only complement inhibitor being trialled in ALS, the table below shows. This approach took a blow when the Champions-ALS trial of Astrazeneca’s Ultomiris was stopped last month owing to lack of efficacy.
Other recent flops have come from Orphazyme’s heat shock protein amplifier arimoclomol, Brainstorm’s autologous cell therapy NurOwn, and Orion’s Simdax po; an intravenous formulation of the latter, a calcium sensitiser, is used in heart failure.
Amylyx hopes for a quick approval in ALS, but might not be the only one. It could soon become clear whether some of the other shots on goal have managed to hit their target.
|Selected ALS projects in mid-to-late-stage clinical development|
|Tofersen||Sod1 antisense oligo||Biogen/Ionis||Valor; Atlas in presymptomatic adults with Sod1 mutation||Valor data due H2 2021; Atlas ends Aug 2026|
|Alsitek (masitinib)||CD117, FGFR3 & PDGFR antagonist||AB Science||AB19001||Ends Dec 2022; study restarted in Aug 2021 after being suspended in Jun 2021|
|Reldesemtiv||Troponin activator||Cytokinetics||Courage-ALS||Ends Dec 2023|
|Jacifusen (ION363)||Fused in sarcoma antisense||Ionis||NCT04768972||Ends Mar 2024|
|AMX0035 (sodium phenylbutyrate + taurursodiol)||Histone deacetylase inhibitor + bax inhibitor||Amylyx||Phoenix not yet recruiting||Amylyx plans US filing based on positive ph2 Centaur data|
|CuATSM||Copper-containing synthetic small molecule||Collaborative Medicinal Development||NCT04082832||Primary completion date Dec 2020 but still recruiting|
|Zilucoplan||Complement factor C5 inhibitor||UCB||HEALEY ALS Platform Trial – Regimen A*||Ends Oct (previously Mar) 2021|
|Verdiperstat||Myeloperoxidase enzyme inhibitor||Biohaven||HEALEY ALS Platform Trial – Regimen B*||Ends Oct (previously Mar) 2021|
|CNM-Au8||Elemental gold nanocrystals||Clene Nanomedicine||HEALEY ALS Platform Trial – Regimen C*; ph2 Rescue-ALS||Healey C ends Oct (previously Mar) 2021; Rescue-ALS data due Q4 2021|
|Pridopidine||Sigma-1 receptor agonist||Prilenia||HEALEY ALS Platform Trial – Regimen D*||Ends Mar 2022|
|MN-166 (ibudilast/Ketas)||Phosphodiesterase inhibitor||Medicinova||Combat-ALS||Ends Dec 2023|
|PrimeC (ciprofloxacin + celecoxib||Antibiotic/Cox-2 inhibitor & NSAID||Neurosense Therapeutics||NCT04165850||Ended Jan 2021|
|ALZT-OP1a (cromolyn + ibuprofen)||Mast-cell stabiliser/NSAID||Aztherapies||NCT04428775||Ended Jul 2021|
|RT001||Synthetic omega-6 fatty acid||Retrotope||NCT04762589||Ends Sep 2021|
|BLZ945||CSF-1 inhibitor||Novartis||NCT04066244||Ends Sep 2021|
|PU-AD||Heat shock protein 90 inhibitor||Samus Therapeutics||NCT04505358||Ends Dec 2021|
|ANX005||Anti-complement factor C1q MAb||Annexon Biosciences||NCT04569435||Data due 2022|
|3K3A-APC||Activated protein C analogue||ZZ Biotech||NCT05039268*||Ends Jan 2022|
|AT-1501||Anti-CD40L MAb||Eledon Pharmaceuticals||NCT04322149||Ends Mar 2022|
|Empaveli||Complement factor C3 inhibitor||Apellis||Meridian||Ends Sep 2022|
|Engensis||HGF gene therapy||Helixmith||Revivals-1A||Ends Dec 2022|
|Trametinib (SNR1611)||Mek inhibitor||Genuv||Ph1/2, NCT04326283||Ends Dec 2022|
|WVE-004||C9orf72 antisense oligo||Wave Life Sciences||Ph1/2 Focus-C9; also includes pts with FTD||Ends Feb 2023|
|RNS60||Oxygen nanobubbles||Revalesio||NCT02988297 (nebulised version)||Ends Dec 2023|
|Q-Cells||Human glial restricted progenitor cells||Q Therapeutics||Ph1/2, NCT02478450||Ends Dec 2023|
|AL001||Sortilin inhibitor||Alector/ Glaxosmithkline||Not available||First pt dosed Sep 2021|
|*Investigator-sponsored study. Source: Evaluate Pharma & clinicaltrials.gov.|
The table in this story has been updated to include Neurosense's PrimeC.