Biogen leads the amyotrophic lateral sclerosis hopefuls

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.

Academic efforts

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.

The table in this story has been updated to include Neurosense's PrimeC.