Axoltis Reports Phase 2 Failure of Experimental ALS Drug
核心洞察
Axoltis (搜索) reported that its SEALS Phase 2 trial of intravenous NX210c in ALS missed the primary endpoint of week-six changes in neurofilament light chain (搜索) and Qalb.
In post-hoc analyses, monthly ALSFRS-R decline at week 10 was 0.77 points with 5 mg/kg and 1.06 with 10 mg/kg versus 1.57 for placebo.
The 51% reduction in functional decline seen with the lower dose reached statistical significance but showed no clear dose-response and requires confirmation.
Axoltis (搜索) Pharma's SEALS Phase 2 study of NX210c in amyotrophic lateral sclerosis (搜索) (ALS) did not meet its primary endpoint. The 82-patient trial randomized participants to intravenous NX210c at 5 mg/kg or 10 mg/kg, or placebo, three times weekly for four weeks, and looked for week-six changes in neurofilament light chain (搜索) (NfL) and Qalb, a measure of blood-brain barrier integrity. Neither biomarker showed a significant treatment effect.
Post-hoc analyses of the ALSFRS-R functional scale were more encouraging. At week 10, monthly functional decline was 0.77 points with the 5 mg/kg dose and 1.06 points with 10 mg/kg, versus 1.57 points for placebo; the lower-dose difference corresponded to a 51% reduction and reached statistical significance, according to the company. At four months, reductions versus placebo were 36% and 32%, respectively. The stronger result came from the lower dose rather than showing a clear dose-response, and the analyses were not the prespecified endpoint in a small, four-week treatment trial. Preliminary SEALS data presented at ENCALS in June had shown ALSFRS-R decline rates of 0.67 points per month with 5 mg/kg, 0.9 with 10 mg/kg and 1.14 with placebo.
NX210c is a synthetic 12-amino-acid peptide derived from SCO-spondin (搜索), a brain protein involved in nervous system development and blood-brain barrier integrity. Axoltis (搜索) is developing it around three proposed effects: restoring the blood-brain barrier, protecting neurons and improving neurotransmission, and pointed to a significant reduction in plasma claudin-5 (搜索) at 10 mg/kg as evidence of target engagement. The company positions the candidate as addressing mechanisms that could apply across a broader ALS population, unlike mutation-specific programs such as Biogen's tofersen, which won accelerated FDA approval for SOD1 (搜索)-ALS in 2023 after initially missing its primary functional endpoint.