latozinemab · program
Latozinemab for Amyotrophic lateral sclerosis
Indications for latozinemab: Frontotemporal dementia · Discontinued Amyotrophic lateral sclerosis · Discontinued
Alector's Phase 2 program of latozinemab (AL001), an anti-sortilin progranulin-elevating monoclonal antibody, in C9orf72-associated amyotrophic lateral sclerosis — terminated October 2022 after enrolling only 5 of 45 planned participants. The registry whyStopped states the sponsor was considering a subsequent ALS study with potentially different inclusion/exclusion criteria, but no follow-up ALS study was ever registered. ALS was part of the July 2021 GSK collaboration scope; after the FTD Phase 3 INFRONT-3 failure (announced 2025-10-21), Alector ended latozinemab development entirely, foreclosing any ALS revival. No ALS efficacy data was reported.
Development timeline
- The Phase 2 ALS study was terminated after enrolling 5 participants. Registry whyStopped: 'The Sponsor is considering a subsequent study in ALS, potentially with different inclusion/exclusion criteria.' No subsequent ALS study was ever registered, and all latozinemab development ended 2025-10-21 after the FTD Phase 3 failure — so this termination date stands as the program's end.
- Trial terminatedAlector terminates the latozinemab Phase 2 in C9orf72-associated ALS after enrolling 5 of 45 planned participants
- Phase 2 study of latozinemab in C9orf72-associated ALS (AL001-ALS-201, NCT05053035) started, targeting 45 participants — the first expansion of the progranulin-elevation hypothesis beyond FTD, two months after the GSK collaboration was announced.
Clinical trials in Amyotrophic lateral sclerosis
NCT05053035AL001-ALS-201Phase 2Discontinuedn=5
A Phase 2 Study to Evaluate AL001 in C9orf72-Associated ALS
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| Latozinemab IV infusion (60 mg/kg every 4 weeks) 60 mg/kg by intravenous infusion every four weeks in INFRONT-2 (open-label Phase 2, dosed for nearly two years) and INFRONT-3 (Phase 3, 96 weeks). Phase 1 (INFRONT-1) used single and multiple ascending IV doses in healthy volunteers and GRN mutation carriers. | Intravenous | Once monthly | — |
Mechanism of action
Human monoclonal antibody against sortilin (SORT1), a Vps10p-domain receptor that binds progranulin and mediates its endocytosis and lysosomal degradation. Latozinemab binds sortilin with high affinity, blocks the progranulin–sortilin interaction and reduces cell-surface sortilin levels, thereby increasing extracellular progranulin concentrations. The ALS rationale rested on progranulin's neurotrophic and TDP-43-pathology-modifying role in C9orf72-associated disease; the program ended before generating efficacy data.
| Target | Action | Affinity |
|---|---|---|
| SortilinprimarySORT1 | Antagonist | —ⓘ |
← Full latozinemab compound page (identity, identifiers, all indications)
Sources
- Latozinemab — Alzforum Therapeutics database profile (mechanism, GSK collaboration, ALS trial history, program discontinuation) — Alzforum (FBRI LLC)
- NCT05053035 (AL001-ALS-201) — Phase 2 of AL001 in C9orf72-associated ALS; TERMINATED 2022-10-28 with 5 enrolled, whyStopped: sponsor considering a subsequent study with different inclusion/exclusion criteria — ClinicalTrials.gov (U.S. National Library of Medicine)