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AMX0035

Phase 3

Amyotrophic Lateral Sclerosis | Small molecule | Neurology |Amylyx Pharmaceuticals, Inc.|Last Updated: Apr 30, 2026

Success Probability

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials5
Total Enrollment1,271

FDA Designations

No designations recorded

Clinical trial landscape

AMX0035 · 8 trials · 14 indications

Phase 3 2Phase 2 6
NCT05619783Extension Study Evaluating The Safety And Tolerability of AMX0035Amyotrophic Lateral Sclerosis
COMPLETED352 Analytics
NCT05021536Phase III Trial of AMX0035 for Amyotrophic Lateral Sclerosis TreatmentAmyotrophic Lateral Sclerosis
ACTIVE NOT_RECRUITING664 Analytics
PHASE3COMPLETED
Extension Study Evaluating The Safety And Tolerability of AMX0035
Amyotrophic Lateral SclerosisUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
Phase III Trial of AMX0035 for Amyotrophic Lateral Sclerosis Treatment
Amyotrophic Lateral SclerosisUnlock trial analytics

Study Endpoints

Primary Endpoints

To assess the Incidence of Treatment-Emergent Adverse Events during treatment with AMX0035
108 weeks

Incidence of all adverse events (AE)s; AEs leading to treatment discontinuation or study withdrawal, and all serious adverse events (SAE)s in participants treated with AMX0035

Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Slope Change
48 weeks

Change in slope of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) over treatment duration. The ALSFRS-R consists of 12 items across 4 subdomains of function (bulbar, fine motor, gross motor, and breathing) with each item scored on a scale from 0 (total loss of function) to 4 (no loss of function). Total scores range from 0 to 48, with higher scores indicating better function.

Change in total (28-item) Progressive Supranuclear Palsy Rating Scale (PSPRS) Score
52 weeks

Assess the impact of AMX0035 on disease progression as measured by the Progressive Supranuclear Palsy (PSP) Rating Scale (PSPRS); Total scores range from 0-96 with higher scores indicating more progressed disease

To evaluate the effect of AMX0035 on residual beta-cell function by monitoring C-peptide levels during a 0-240 minutes mixed-meal tolerance test (MMTT)
24 weeks

* C-peptide area under the curve (AUC) response at Week 24 using a 0-240 minute MMTT * Change from Baseline in area under the curve (AUC) in delta C-peptide at Week 24 using a 0-240 minute MMTT

To assess the safety and tolerability of AMX0035 administered orally for up to 208 weeks in adult participants with Wolfram syndrome
208 weeks

* Incidence and severity of Adverse Events and Serious Adverse Events * Incidence of abnormalities in clinical laboratory assessments

Treatment emergent Adverse Events
Through study completion an average of 1 year

Rate of treatment emergent adverse events during AMX0035 therapy

Number of Participants With Treatment-Emergent Adverse Event (TEAEs)
From first dose to 24 weeks

Comparison between the AMX0035 Group and Placebo of the number of participants with TEAEs

Effect of Treatment on a Global Composite Statistical Test of Cognition, Function, and Neuroanatomy (GST)
24 weeks

Change from Baseline in GST (global statistical test combining three measures relevant to disease trajectory (cognition \[MADCOMS: Mild/Moderate Alzheimer's Disease Composite Score\], function \[FAQ: Functional Activities Questionnaire\], and total hippocampal volume on magnetic resonance imaging)) for AMX0035 relative to placebo. For MADCOMS and FAQ, a higher score indicates a worse outcome. A larger hippocampal volume is better, so it was reversed before being normalized. Each of the three were normalized against respective baseline means and standard deviations. The mean of the three normalized scores is the final GST. A higher GST score indicates a worse outcome. Standard deviations above the mean are worse; standard deviations below the mean are better. The expected value of the GST at baseline is 0 because it is the mean of three z-scores whose expected values at baseline are 0. AD is multifaceted and the GST was designed to be sensitive to changes in multiple dimensions.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
From the Baseline Visit in the OLE study through Week 132 or the Early Discontinuation (Final Safety) Visit for each participant (for up to approximately 132 weeks)

Number of participants with TEAEs from baseline in the OLE study through the last participant's last visit in the OLE

Number of Participants With Adverse Events
24 Weeks

Comparison Between Groups of Number of Participants With Adverse Events Until Planned Completion

Number of Participants in Each Group Able to Remain on Study Drug Until Planned Discontinuation
24 weeks

A comparison of the number of participants in each group able to remain on study drug until planned discontinuation between groups

Secondary Endpoints

To assess the impact of long-term treatment with AMX0035 on survival
108 weeks
Participant Quality of Life (QOL)
48 weeks
Assess Long-Term Survival
3 years from LPI
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
ActiveEXPERIMENTALAll participants will be treated with oral (or feeding tube) AMX0035 (a fixed-dose combination of Sodium Phenylbutyrate (PB) and taurursodiol). All participants will take 2 sachets daily (one morning dose and one evening dose) starting on Day 1, for the duration of the study (if twice a day dosing is poorly tolerated, dosing interruptions and reductions are further discussed in section 6.3) AMX0035 will be supplied by Amylyx as a carton box containing approximately 1 month supply of single use sachets. Each AMX0035 sachet contains active ingredients in a powder formulation with 3 g PB and 1 g taurursodiol. AMX0035 powder is mixed with water and taken orally (or via feeding tube).
PlaceboPLACEBO_COMPARATORPlacebo administered by mouth or via feeding tube for 48 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating
AMX0035EXPERIMENTALPlacebo administered by mouth or via feeding tube for 48 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating
AMX-0035 long term treatment extensionEXPERIMENTALAMX0035 administered twice daily p.o.
Active (AMX0035)ACTIVE_COMPARATORAMX0035 twice daily--a combination of Sodium Phenylbutyrate (3g) and Taurursodiol (1g)

Interventions

NameTypeDescription
AMX0035DRUGCombination of 3 g phenylbutyrate and 1 g taurursodiol
PlaceboOTHERMatching Placebo Comparator
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites46

Inclusion Criteria: 1. Previous participation in Study A35-004 (PHOENIX), including completion of the randomized controlled phase through Week 48 (this timepoint may be upcoming at the time of screening). Participants who do not complete randomized-controlled phase through Week 48 for medical reaso...

Countries:BelgiumFranceGermanyIrelandItalyNetherlandsPolandPortugalSpainSwedenUnited KingdomUnited States
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Recent Changes (Last 90 Days)

MEDIUMMay 31, 2026NCT06122662TRIAL_REMOVED: changed
MEDIUMMay 31, 2026NCT06122662TRIAL_REMOVED: changed
MEDIUMMay 31, 2026NCT06122662TRIAL_REMOVED: changed
MEDIUMMay 26, 2026NCT05676034primaryCompletionDate: changed
LOWMay 26, 2026NCT05021536primaryCompletionDate: changed
HIGHMay 26, 2026NCT06122662Status: ACTIVE_NOT_RECRUITING → COMPLETED
LOWMay 24, 2026NCT05676034studyFirstPostDate: changed
LOWMay 24, 2026NCT05021536studyFirstPostDate: changed
LOWMay 24, 2026NCT06122662studyFirstPostDate: changed

Frequently asked questions about AMX0035

What is AMX0035 used for?

AMX0035 is an investigational small molecule being developed for Wolfram Syndrome, Amyotrophic Lateral Sclerosis, Progressive Supranuclear Palsy, and Alzheimer Disease. It is currently in Phase 2 clinical development and has not been approved by the FDA.

Who makes AMX0035?

AMX0035 is being developed by Amylyx Pharmaceuticals, Inc., a biopharmaceutical company traded on the NASDAQ under the ticker symbol AMLX. The company is conducting clinical trials to evaluate the drug's safety and efficacy in several neurological conditions.

What phase is AMX0035 in?

AMX0035 is currently in Phase 2 clinical development. It has completed Phase 2 trials for Amyotrophic Lateral Sclerosis and Alzheimer Disease, and an active Phase 3 trial for ALS is ongoing but not yet recruiting participants.

What clinical trials is AMX0035 in?

AMX0035 has been studied in several clinical trials, including NCT03127514, a completed Phase 2 trial in ALS with 137 participants, and NCT03533257, a completed Phase 2 trial in Alzheimer's Disease with 95 participants. An active Phase 3 trial, NCT05021536, is ongoing for ALS with 664 participants.

Is AMX0035 the same as any other drug?

AMX0035 is not known by any alternative names. It is a unique investigational compound developed by Amylyx Pharmaceuticals for the treatment of neurological disorders.