masitinib · program

Masitinib for Alzheimer's disease

Phase 3SuspendedAB Science (AB)

Indications for masitinib: Amyotrophic lateral sclerosis · Phase 3 Multiple sclerosis · Phase 3 Alzheimer's disease · Phase 3

Masitinib as an adjunct to cholinesterase inhibitors and/or memantine in mild-to-moderate Alzheimer's disease - a neuroimmune (mast cell + microglia) approach distinct from the amyloid pathway. The pivotal AB09004 study (Phase 3 per registry; a four-arm 'Phase 2b/3' per AB Science; 721 registered, ~635 analyzed across the two independent parallel groups) reported a positive result in December 2020, published in Alzheimer's Research & Therapy in February 2023: masitinib 4.5 mg/kg/day significantly improved ADAS-cog vs placebo at week 24 (between-group difference -2.15, 97.5% CI -3.48 to -0.81, p<0.001), with the ADCS-ADL co-primary difference +1.82 (97.5% CI -0.15 to 3.79, p=0.038); the independent titrated 6.0 mg/kg/day group was inconclusive. A confirmatory Phase 3, AB21004 (target 600 patients with MILD AD on stable standard of care, primary endpoint iADRS change at week 24), received its first agency authorizations in October 2022 and FDA authorization in November 2022 - but has never started: the registration (NCT05564169) remains not-yet-recruiting with a stale estimated start of June 2026. In April 2026 AB Science deprioritized the indication, stating Alzheimer's (like MS) requires commercial capabilities it lacks and that its Phase 3 development will be 'pursued through partnerships', while focusing internal resources on ALS and AML; unlike the MS trial, AB21004 was not among the studies formally discontinued in July 2026. The program is recorded as suspended pending a partner. EMA has never reviewed masitinib in Alzheimer's disease.

Data current as of

Development timeline

Phase 3Jan 2012 – Apr 2026
  1. AB Science deprioritized Alzheimer's disease in its strategic reorganization: new-patient recruitment voluntarily halted across its European studies, internal resources focused on ALS Phase 3 + AB8939 AML, and 'continuation, via partnerships, of Phase III development in multiple sclerosis and Alzheimer's disease, indications requiring commercial capabilities that AB Science does not possess in-house' (restated in the 2026-05-13 annual results). AB21004 had still not started and was not among the trials formally discontinued on 2026-07-10. Program suspended pending a partner; flip to discontinued if the sponsor abandons the indication.↗
  2. Trial registeredConfirmatory Phase 3 AB21004 in mild Alzheimer's disease registered (NCT05564169) - never started
  3. metAB09004 topline (2020-12-16): masitinib 4.5 mg/kg/day met the ADAS-cog primary endpoint in mild-to-moderate Alzheimer's disease as add-on to standard of care (published values: between-group difference -2.15, 97.5% CI -3.48 to -0.81, p<0.001; ADCS-ADL co-primary difference +1.82, p=0.038); the independent titrated 6.0 mg/kg/day group was inconclusive.↗
  4. Pivotal AB09004 (NCT01872598) started per ClinicalTrials.gov (January 2012, month precision): randomized, double-blind, placebo-controlled, four-arm study of masitinib 4.5 mg/kg/day, 4.5-to-6.0 titrated, and (initially) 3.0 mg/kg/day vs placebo, as add-on to cholinesterase inhibitor and/or memantine in mild-to-moderate AD; co-primary ADAS-Cog and ADCS-ADL at week 24. Registered PHASE3; AB Science communicates it as 'Phase 2b/3'.
Phase 2Jul 2008
  1. Exploratory Phase 2 AB04024 (NCT00976118, n=34): oral masitinib 3 or 6 mg/kg/day vs placebo as adjunct in mild-to-moderate AD; primary completion July 2008 (ADAS-Cog at week 24). Published as Piette et al., Alzheimers Res Ther 2011.

Readouts

  • 2020-12-16ReportedTopline datametNCT01872598

    AB09004 topline (2020-12-16): masitinib 4.5 mg/kg/day met the ADAS-cog primary endpoint in mild-to-moderate Alzheimer's disease as add-on to standard of care (published values: between-group difference -2.15, 97.5% CI -3.48 to -0.81, p<0.001; ADCS-ADL co-primary difference +1.82, p=0.038); the independent titrated 6.0 mg/kg/day group was inconclusive. ↗

Clinical trials in Alzheimer's disease

NCT05564169AB21004Phase 3Activen=600

Masitinib as Add-on Therapy in Patients With Mild Alzheimer's Disease Treated With Standard of Care (confirmatory Phase 3, iADRS at week 24, target n=600)

Started Jun 2026· Primary completion Dec 2028· 📍 9 sites across 2 countries (Spain, France)

NCT01872598AB09004Phase 3Completedn=721

Masitinib in Patients With Mild to Moderate Alzheimer's Disease (four-arm, add-on to cholinesterase inhibitor and/or memantine; co-primary ADAS-Cog and ADCS-ADL at week 24)

Started Jan 2012· Primary completion Dec 2020· 📍 6 sites across 6 countries (Greece, Romania, Poland, Ukraine)

NCT00976118AB04024Phase 2Completedn=34

Activity of Masitinib (AB1010) in Mild to Moderate Alzheimer's Disease (adjunct to standard of care, ADAS-Cog at week 24)

Started Feb 2006· Primary completion Jul 2008

Formulations

FormulationRouteRegimenPharmacokinetics
Masitinib (mesylate) oral tablet, weight-based twice-daily dosing
Weight-based daily dose given orally as two intakes. Alzheimer's disease: AB09004 tested 4.5 mg/kg/day and 4.5 titrated to 6.0 mg/kg/day after 12 weeks (plus a 3.0 mg/kg/day arm), always as add-on to cholinesterase inhibitor and/or memantine; confirmatory AB21004 planned 3.0 mg/kg/day escalated to 4.5 mg/kg/day after 4 weeks as add-on to standard of care.
OralTwice daily—

Mechanism of action (compound-wide)

Orally bioavailable, selective tyrosine kinase inhibitor targeting wild-type and juxtamembrane-mutant KIT (c-Kit), PDGFR alpha and beta, and the Src-family kinase Lyn, with weak activity against Abl and Src and no significant inhibition of most other kinases screened (Dubreuil et al., PLoS ONE 2009: recombinant-enzyme IC50 0.20 uM for wild-type KIT vs >10 uM for FGFR3 and FAK). In Alzheimer's disease the proposed mechanism is modulation of the innate neuroimmune system - mast cells (via KIT) and microglia (via Lyn-family kinases) - as an adjunct to symptomatic standard of care (cholinesterase inhibitors and/or memantine), per the AB09004 trial report (Dubois et al., Alzheimer's Research & Therapy 2023).

TargetActionAffinity
KITprimaryKITInhibitorIC50 200 nMⓘ
LynLYNInhibitorIC50 510 nMⓘ
PDGFR-alphaPDGFRAInhibitorIC50 540 nMⓘ
PDGFR-betaPDGFRBInhibitorIC50 800 nMⓘ

← Full masitinib compound page (identity, identifiers, all indications)

Sources

  1. AB Science provides an update on its clinical program: voluntary temporary halt of European trials; Alzheimer's (and MS) Phase 3 development to continue via partnerships (2026-04-16) — AB Science SA
  2. Dubreuil P, et al. Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT. PLoS ONE. 2009;4(9):e7258 — PLoS ONE via PubMed Central
  3. NCT00976118 (AB04024) - Activity of Masitinib (AB1010) in Mild to Moderate Alzheimer's Disease (Phase 2, n=34, completed) — ClinicalTrials.gov (U.S. National Library of Medicine)
  4. NCT01872598 (AB09004) - Masitinib in Patients With Mild to Moderate Alzheimer's Disease (Phase 3, n=721, completed 2020-12) — ClinicalTrials.gov (U.S. National Library of Medicine)
  5. NCT05564169 (AB21004) - Masitinib as Add-on Therapy in Patients With Mild Alzheimer's Disease (confirmatory Phase 3, target n=600, not yet recruiting; last update 2025-10-03) — ClinicalTrials.gov (U.S. National Library of Medicine)
  6. Positive confirmatory Phase 2b/3 study AB09004 with masitinib in Alzheimer's disease (2020-12-16) — AB Science SA