masitinib · program

Masitinib for Amyotrophic lateral sclerosis

Phase 3ActiveAB Science (AB)
  • EU Orphan Designation For ALS (Referenced In The EMA Alsitek Refusal Q&A); Swissmedic Orphan Drug Status For ALS (2022-12-27, Per AB Science)

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

Masitinib, an oral KIT/PDGFR/Lyn tyrosine kinase inhibitor targeting mast cells and microglia, as add-on to riluzole in amyotrophic lateral sclerosis - AB Science's lead indication and, since April 2026, one of its only two priority programs. The Phase 2/3 AB10015 study (n=394) met its prespecified primary analysis: in 'normal progressors' (ALSFRS-R decline <1.1 points/month pre-baseline), masitinib 4.5 mg/kg/day slowed 48-week ALSFRS-R decline by 3.4 points vs placebo (27% slowing, p=0.016), with convergent sensitivity analyses and a long-term median overall survival benefit of over 2 years in follow-up analyses. Regulatory history is chequered: the first EU application (Alsitek) was refused in 2018 (arbitrary subgrouping, site-inspection and data-handling concerns per CHMP); a second, conditional MAA filed August 2022 received a CHMP negative opinion on 27 June 2024, confirmed on re-examination 17 October 2024 (subgroup-reliability concerns); Health Canada issued a Notice of Non-compliance-Withdrawal in February 2024 (reconsideration eligibility granted April 2024). The path forward agreed with regulators is a new confirmatory Phase 3, AB23005 (n=408, 1:1, masitinib 4.5 mg/kg/day + riluzole vs placebo + riluzole, 48-week ALSFRS-R primary endpoint, enrolling only normal progressors without complete loss of function, edaravone allowed as a stratification factor) - authorized by FDA and by the first EU countries (Spain, Greece, Slovenia, via CTIS) as announced 2025-07-24, registered as NCT07174492 in September 2025, and de-risked by a EUR 25M (extendable to EUR 39M) clinical-trial-failure insurance policy from Lloyd's Syndicate 1902 (binding offer, April 2026, activatable until 2026-12-31). As of 2026-07-10 AB23005 had not yet dosed: AB Science is submitting a substantial protocol amendment and will re-seek authorization to start. The earlier confirmatory Phase 3 AB19001 (started 2021, 495 planned) remains registry-listed as recruiting but has been effectively superseded by AB23005 and is subject to the April 2026 voluntary halt of European recruitment.

Data current as of

Development timeline

Phase 3Feb 2021 – Dec 2027
  1. UpcomingClinicalTrials.gov estimated primary completion of confirmatory Phase 3 AB19001 (NCT03127267): December 2027 (registry estimate, not company guidance).
  2. FinancingEUR 25M clinical-trial-failure insurance secured for the ALS Phase 3 (AB23005)↗
  3. Trial registeredNew confirmatory Phase 3 AB23005 registered on ClinicalTrials.gov (NCT07174492)
  4. CHMP confirmed its negative opinion on the conditional MAA after re-examination (initial negative opinion 2024-06-27); the EU filing is closed and the program reverts to confirmatory Phase 3. The agreed path forward is the new confirmatory study AB23005 (FDA + first EU authorizations announced 2025-07-24; registered as NCT07174492 on 2025-09-16; per the 2026-07-10 update it has not yet begun and will start after a substantial protocol amendment is re-authorized). Health Canada had issued a Notice of Non-compliance-Withdrawal on 2024-02-26 (reconsideration eligibility granted 2024-04-03).↗
  5. CHMP opinionCHMP confirms refusal of masitinib conditional MAA in ALS after re-examination↗
  6. Confirmatory Phase 3 AB19001 (NCT03127267) actual start date per ClinicalTrials.gov: masitinib 4.5 or 6.0 mg/kg/day + riluzole vs placebo + riluzole, 48-week ALSFRS-R primary endpoint. Context: AB10015 had completed (primary completion 2016-12-05) and the first EU MAA (Alsitek) had been refused in 2018. Note: a company-wide voluntary hold on masitinib studies ran 2021-06-01 until resumption authorizations later in 2021 (FDA authorized resuming AB19001 enrollment on 2021-11-18).
Filed (NDA)Aug 2022 – Jun 2024
  1. CHMP opinionCHMP adopts negative opinion on the conditional marketing authorisation of masitinib in ALS↗
  2. AB Science filed an application for conditional marketing authorization to the EMA for masitinib in ALS (based on AB10015 plus long-term survival follow-up), while confirmatory AB19001 continued. A Health Canada NDS was also under review in this period (filing authorized 2022-02-21; Notice of Deficiency 2022-12-13).↗
  3. NDA/BLA filedAB Science files EU conditional marketing authorisation application for masitinib in ALS↗
Phase 2/3Apr 2013 – Jul 2019
  1. metAB10015 Phase 2/3 published (Mora et al., ALS-FTD 2020, epub 2019-07-07): in the prespecified primary population (normal progressors, ALSFRS-R decline <1.1 pts/month), masitinib 4.5 mg/kg/day + riluzole slowed 48-week ALSFRS-R decline by 3.4 points vs placebo (95% CI 0.65-6.13, p=0.016; 27% slowing), with significant ALSAQ-40, FVC and time-to-event secondaries; no effect in the broader population or 3.0 mg/kg/day cohorts.↗
  2. CHMP opinionCHMP adopts negative opinion on Alsitek (masitinib), the first EU marketing application in ALS↗
  3. AB10015 (NCT02588677) start per ClinicalTrials.gov (April 2013, month precision): randomized, double-blind, placebo-controlled Phase 2/3 of masitinib 3.0 or 4.5 mg/kg/day + riluzole vs placebo + riluzole in 394 ALS patients, with a blinded Phase 2 -> Phase 2/3 transition and a prospectively-declared primary population of 'normal progressors' on 4.5 mg/kg/day.

Readouts

  • December 2027AnticipatedRegistry resultsNCT03127267

    ClinicalTrials.gov estimated primary completion of confirmatory Phase 3 AB19001 (NCT03127267): December 2027 (registry estimate, not company guidance).

  • 2019-07-07ReportedFull resultsmetNCT02588677

    AB10015 Phase 2/3 published (Mora et al., ALS-FTD 2020, epub 2019-07-07): in the prespecified primary population (normal progressors, ALSFRS-R decline <1.1 pts/month), masitinib 4.5 mg/kg/day + riluzole slowed 48-week ALSFRS-R decline by 3.4 points vs placebo (95% CI 0.65-6.13, p=0.016; 27% slowing), with significant ALSAQ-40, FVC and time-to-event secondaries; no effect in the broader population or 3.0 mg/kg/day cohorts. ↗

Clinical trials in Amyotrophic lateral sclerosis

NCT07174492AB23005Phase 3Activen=412

Efficacy and Safety of Masitinib in Combination With SoC Versus Placebo in Combination With SoC in the Treatment of ALS (confirmatory Phase 3, n=408)

Started Jan 2026· Primary completion Dec 2028· 📍 1 site across 1 country (Greece)

NCT03127267AB19001Phase 3Recruitingn=495

Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients (masitinib 4.5 or 6.0 mg/kg/day + riluzole)

Started Feb 2021· Primary completion Dec 2027· 📍 56 sites across 17 countries (France, Italy, Spain, United States)

NCT02588677AB10015Phase 2/3Completedn=394

Masitinib in Combination With Riluzole for the Treatment of Patients Suffering From Amyotrophic Lateral Sclerosis (ALS)

Started Apr 2013· Primary completion Dec 2016· 📍 1 site across 1 country (Spain)

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 announces that it has filed an application for conditional marketing authorization to EMA for masitinib in the treatment of ALS (2022-08-24) — AB Science SA
  2. 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
  3. AB Science provides an update on the application for conditional marketing authorisation of masitinib in ALS - CHMP negative opinion (2024-06-28) — AB Science SA
  4. AB Science provides an update on the application for conditional marketing authorisation of masitinib in ALS - refusal confirmed after re-examination (2024-10-17) — AB Science SA
  5. Alsitek (masitinib) - EPAR: CHMP negative opinion 2018-04-18; re-examination request withdrawn; marketing authorisation refused 2018-07-26 — European Medicines Agency
  6. 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
  7. Mora JS, et al. Masitinib as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomized clinical trial. Amyotroph Lateral Scler Frontotemporal Degener. 2020;21(1-2):5-14 (epub 2019-07-07) — Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration (Taylor & Francis) / PubMed
  8. 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)
  9. NCT02588677 (AB10015) - Masitinib in Combination With Riluzole for the Treatment of Patients Suffering From ALS (Phase 2/3, n=394, completed) — ClinicalTrials.gov (U.S. National Library of Medicine)
  10. NCT03127267 (AB19001) - Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients (Phase 3, est. n=495, recruiting; last update 2025-09-12) — ClinicalTrials.gov (U.S. National Library of Medicine)
  11. NCT07174492 (AB23005) - Efficacy and Safety of Masitinib in Combination With SoC Versus Placebo in ALS (confirmatory Phase 3, est. n=412, not yet recruiting) — ClinicalTrials.gov (U.S. National Library of Medicine)