CLINICAL TRIALS PROFILE FOR RILUZOLE

All Clinical Trials for RILUZOLE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00013624 ↗	Riluzole to Treat Parkinson's Disease	Completed	National Institute of Neurological Disorders and Stroke (NINDS)	Phase 2	2001-03-01	This study will evaluate the effects of the drug riluzole on Parkinson's disease symptoms and on dyskinesias (involuntary movements) that develop as a result of long-term treatment with levodopa. Riluzole blocks the action of the chemical messenger glutamate, thought to be involved in producing Parkinson's symptoms. The drug is currently approved to treat amyotrophic lateral sclerosis, another neurologic condition. Patients with relatively advanced Parkinson's disease between 20 and 80 years of age may be eligible for this 4-week study. Participants will have a complete medical history and physical examination, and a detailed neurological evaluation. The evaluations will include blood tests and an electrocardiogram, and possibly brain magnetic resonance imaging (MRI), CT scan, and chest X-ray. Participants will, if possible, stop taking all antiparkinsonian medications except levodopa (Sinemet) for one month before the study begins and throughout its duration. For the first 1 to 3 days, patients will be admitted to the NIH Clinical Center to undergo a levodopa "dose-finding" procedure. For this study, patients will stop taking their oral Sinemet and instead will have levodopa infused through a vein for up to 8 hours/day. During the infusions, the levodopa dose will be increased slowly until either 1) parkinsonian symptoms improve, 2) unacceptable side effects occur, or 3) the maximum study dose is reached. Symptoms will be monitored frequently to find two infusion rates: 1) one that is less than what is needed to relieve symptoms (suboptimal rate), and 2) one that relieves symptoms but may produce dyskinesias (optimal rate). When the dose-finding phase is completed, treatment will begin. Patients will take riluzole or placebo (a look-a-like pill with no active ingredient) twice a day, along with their regular Sinemet, for 3 weeks. (All participants will receive placebo at some time during the study, and some patients will receive only placebo throughout the entire 4 weeks.) At the end of each week, patients will be readmitted to the hospital and receive the previous week's dose of riluzole or placebo in combination with a levodopa infusion at the rate determined in the dose-finding phase of the study. The procedure for the infusion will be the same as that for the dose-finding phase. The dose of riluzole will be increased until the optimum dose has been achieved or until side effects occur (at which time the dose will be lowered or the drug stopped). Throughout the study, parkinsonian symptoms and dyskinesias will be evaluated using standardized rating scales and blood samples will be drawn periodically to measure drug levels.
NCT00026052 ↗	Riluzole to Treat Major Depression	Completed	National Institute of Mental Health (NIMH)	Phase 2	2001-11-01	This study will examine the safety and effectiveness of the drug riluzole (Rilutek® (Registered Trademark)) for short-term treatment of depression symptoms, such as depressed mood, psychomotor retardation, and excessive sleeping. Despite the availability of a wide range of antidepressant drugs, studies indicate that 30 to 40 percent of patients with major depression do not respond to first-line antidepressant treatment with drugs such as fluoxetine, upropion, venlafaxine and others. Riluzole, which is approved by the Food and Drug Administration (FDA) for amyotrophic lateral sclerosis (ALS), causes chemical changes in the brain that may also have antidepressant properties. Patients between 18 and 70 years of age with major depressive disorder without psychotic features may be eligible for this 2-stage 7-week study. Candidates will be screened with a medical history and physical examination, including an electrocardiogram (EKG), blood and urine tests, and a psychiatric evaluation. A blood or urine sample will be tested for illegal drugs.Women of childbearing potential will have a pregnancy test. Participants will complete stage 1 of the study, which lasts 1 week, and may then continue with stage 2 for an additional 6 weeks. At the start of the study, patients will be tapered off all psychiatric medicines and will begin treatment with a placebo (a sugar pill formulated to look like the active drug). At some point, they will be switched from placebo to riluzole. In addition, participants will undergo the following procedures: - Physical examination and electrocardiograms (EKG) at the beginning and end of the study, with vital signs (temperature, blood pressure and heart rate) checked daily - Weekly 1-hour interviews consisting of psychiatric and psychomotor rating scales to assess treatment response - Weekly blood tests to measure blood levels of riluzole and evaluate drug side effects At the end of the study, participants' psychiatric status will be reassessed and appropriate long-term psychiatric treatment arranged. Patients, ages 18 to 70 with a diagnosis of major depression without psychotic features, will in this pilot study (single arm, single blind) receive riluzole (50-200 mg/day) for a period of 6 weeks. Acute efficacy will be determined by demonstrating a greater response rate using specified criteria. Approximately 25 patients will enter the study to obtain 22 subjects who complete the 6 weeks of acute riluzole treatment. Therefore, if 7/22 patients or greater have greater than 50% improvement on the primary efficacy measure, then based on statistically guidelines from the Optimal Two Stage Design for Clinical Trials, a controlled trial would be indicated to scientifically confirm the signal observed in the single arm trial.
NCT00047723 ↗	Minocycline to Treat Amyotrophic Lateral Sclerosis	Completed	National Institute of Neurological Disorders and Stroke (NINDS)	Phase 3	2003-01-01	The purpose of this trial is to test the safety, tolerability, and effectiveness of minocycline compared to placebo in patients with amyotrophic lateral sclerosis (ALS).
NCT00054704 ↗	Riluzole to Treat Depression in Bipolar Disorder	Terminated	National Institute of Mental Health (NIMH)	Phase 2	2003-02-01	This study examines if Riluzole, FDA approved for ALS, will improve symptoms of depression in Bipolar Disorder. Purpose: This study will examine the safety and effectiveness of riluzole (Rilutek trademark) for short-term treatment of depression symptoms, such as depressed mood, psychomotor retardation, and excessive sleeping in patients with bipolar disease. Riluzole is approved by the Food and Drug Administration (FDA) to treat amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease). Preliminary findings of a study using riluzole to treat acute depression in patients with unipolar depression indicate that it may have antidepressant properties in some patients. Patients between 18 and 70 years of age with bipolar I or II disorder without psychosis may be eligible for this 8-week study. Candidates must be currently depressed, must have had at least one previous major depressive episode, and must have failed to improve with prior treatment with at least one antidepressant. They will be screened with a medical history, physical examination, electrocardiogram (EKG), blood and urine tests, and psychiatric evaluation. A blood or urine sample will be analyzed for illegal drugs. Women of childbearing potential will have a pregnancy test. Participants will begin an 8-week course of treatment, starting with a placebo (a sugar pill formulated to look like the active drug) and, at some point, switching to riluzole. In addition to drug treatment, participants will undergo the following procedures: Physical examination and electrocardiogram (EKG) at the beginning and end of the study; Weekly check of vital signs (temperature, blood pressure and heart rate); Weekly 1-hour interviews consisting of psychiatric and psychomotor rating scales to assess treatment response; Weekly blood tests to measure blood levels of riluzole and evaluate drug side effects. At the end of the study, participants' psychiatric status will be reassessed and appropriate long-term psychiatric treatment arranged. Atendemos pacientes de habla hispana. We enroll eligible participants locally and from around the country. Travel arrangements are provided and costs covered by the National Institute of Mental Health (NIMH). (Arrangements vary by distance and by specific study.) After completing the study participants receive short-term follow-up care while transitioning back to a provider.
NCT00202397 ↗	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia	Completed	S. Andrea Hospital	Phase 2	2005-06-01	Cerebellar disorders are often disabling and symptomatic therapies are limited to few options that are partially effective. It seems therefore appropriate to search for additional approaches. Purkinje cells are the sole output of the cerebellar cortex: they project inhibitory signals to the deep cerebellar nuclei (DCN), which have a critical role in cerebellar function and motor performance. DCN neurons fire spontaneously in the absence of synaptic input from Purkinje neurons and modulation of the DCN response by Purkinje input is believed to be responsible for coordination of movement. Recent evidences support the notion that an increase in DCN excitability may be an important step in the development of cerebellar ataxia and point to the underlying molecular mechanisms: the inhibition of small-conductance calcium-activated potassium (SK) channels, that causes an increase of the firing frequency in DCN, correlates with cerebellar ataxia. The rationale of the present project is that SK channel openers, such as riluzole, may have a beneficial effect on cerebellar ataxia. The researchers propose to perform a pilot study investigating safety and efficacy of riluzole, an approved treatment for amyotrophic lateral sclerosis, as a symptomatic approach in patients with chronic cerebellar ataxia.
NCT00211224 ↗	Neuroprotection and Natural History in Parkinson's Plus Syndromes (NNIPPS)	Terminated	Assistance Publique - Hôpitaux de Paris	Phase 3	2000-04-01	NNIPPS is a clinical trial of riluzole (a drug previously shown to slow down the rate of progression og amyotrophic lateral sclerosis-ALS; Lou Gehrig's disease) involving nearly 800 people diagnosed with the 'parkinson plus' syndromes of multiple system atrophy (MSA) and progressive supranuclear plasy (PSP). In addition to showing whether riluzole is helpful in MSA and PSP, NNIPPS will improve criteria for making an accurate and early diagnosis, for assessing the rate of progression, and will advance understanding of the biology of these disabling and progressive neurodegenerative diseases.

Clinical Trial Conditions for RILUZOLE

Condition Name

Condition Name for RILUZOLE
Intervention	Trials
Amyotrophic Lateral Sclerosis	56
Amyotrophic Lateral Sclerosis (ALS)	12
ALS	9
Obsessive-compulsive Disorder	7

Condition MeSH

Condition MeSH for RILUZOLE
Intervention	Trials
Amyotrophic Lateral Sclerosis	74
Motor Neuron Disease	67
Sclerosis	59
Disease	14

Clinical Trial Locations for RILUZOLE

Trials by Country

Trials by Country for RILUZOLE
Location	Trials
United States	313
Canada	52
Germany	41
Australia	21
United Kingdom	18

Trials by US State

Trials by US State for RILUZOLE
Location	Trials
California	20
Maryland	20
Texas	16
Arizona	15
Massachusetts	15

Clinical Trial Progress for RILUZOLE

Clinical Trial Phase

Clinical Trial Phase for RILUZOLE
Clinical Trial Phase	Trials
PHASE4	1
PHASE3	2
PHASE2	5

Clinical Trial Status

Clinical Trial Status for RILUZOLE
Clinical Trial Phase	Trials
Completed	75
Recruiting	22
Terminated	16

Clinical Trial Sponsors for RILUZOLE

Sponsor Name

Sponsor Name for RILUZOLE
Sponsor	Trials
Yale University	8
National Institute of Mental Health (NIMH)	7
Cytokinetics	6

Sponsor Type

Sponsor Type for RILUZOLE
Sponsor	Trials
Other	221
Industry	54
NIH	17

Riluzole (Rilutek, generic) clinical trials update, market analysis, and exclusivity timeline

Last updated: July 24, 2026

Riluzole is an established oral glutamate-modulating therapy for amyotrophic lateral sclerosis (ALS). In the US, riluzole’s key patent and exclusivity protection has largely run out; current competitive dynamics center on generic supply, label expansion into subpopulations, and incremental value from dosing convenience rather than new chemical entity protection. Clinical trial activity remains concentrated in combination regimens, biomarkers, and real-world outcomes rather than definitive new registrational programs for riluzole monotherapy.

What clinical trials are updating for riluzole in 2024–2026?

Riluzole’s modern clinical pipeline is dominated by investigator-sponsored or sponsor-backed studies evaluating riluzole as a background standard-of-care. The most common study structures are add-on arms, combination drug testing, and observational cohorts that use riluzole as a baseline covariate.

Are there new phase 3 trials for riluzole?

No new riluzole monotherapy phase 3 registrational trials are driving major regulatory milestones in the 2024–2026 window. Program emphasis is on:

• ALS combination strategies (riluzole plus another agent)
• Mechanistic studies using riluzole to anchor pharmacology while testing new targets
• Post-marketing observational studies on survival endpoints, tolerability, and adherence

What endpoints are most used in riluzole-centered ALS trials?

Commonly reported endpoints include:

• ALSFRS-R change over time
• Time-to-event measures such as tracheostomy, ventilatory support, or death
• Respiratory function and survival proxies
• Biomarker trajectories (neuroinflammation, neurofilament light, glutamate handling proxies)
• Safety signals focused on hepatotoxicity screening, GI tolerability, and discontinuation rates

What is the regulatory impact of these trials?

Because riluzole is already approved and broadly generic, most new studies influence:

• Scientific rationale and prescribing behavior
• Label-supporting evidence for combination care
• Guideline positioning, rather than new approvals for riluzole itself

How big is the riluzole ALS market and what drives demand?

Riluzole is sold as a foundational ALS therapy with a stable demand profile that tracks diagnosed ALS prevalence and persistence to standard-of-care use.

Where does riluzole revenue come from?

Demand is driven by:

• Volume: chronic, long-duration use in a large treated patient pool relative to newer ALS therapies
• Prescribing inertia: riluzole is long-standing, with low switching friction
• Multidisciplinary care patterns: many ALS clinics default to riluzole alongside other agents
• Price erosion: generic competition compresses net revenue per unit, shifting growth to patient volume and supply stability

How does generic pricing affect market projections?

Riluzole’s revenue outlook is constrained by generic penetration and price competition, so market growth depends mainly on:

• Patient incidence and survival trends
• Procurement and payer contracting that preserve low-cost access
• Supply continuity and manufacturing efficiency

Market sizing approach (how projections are typically modeled)

For an established generic:

• Treat incidence and prevalent population as the demand base
• Convert treated patient counts into tablets/day equivalents using labeled dosing schedules
• Apply net price assumptions that reflect ongoing generics and contracting
• Subtract switching risk to alternative standard regimens only if clinically relevant practice changes occur

What market trajectory should be expected for riluzole through 2029?

The expected trajectory is flat-to-slightly down in net revenue terms, with volume either flat or modestly up depending on ALS epidemiology and survival.

Base-case commercial projection (directional)

• Units: modest growth potential tied to prevalence and sustained use as background therapy
• Net sales: decline or flat-to-low growth because generic net pricing typically drifts downward over time
• Share: stable among multiple generic suppliers unless shortages or major contracting changes occur

Upside and downside levers

Upside:

• Longer treated durations due to improved ALS survival and broader access
• Combination care that maintains riluzole as a default backbone

Downside:

• Rapid shift to alternative foundational regimens in a subset of patients
• Further aggressive price compression in major markets
• Supply disruptions that reduce realized volumes

How does riluzole compare with edaravone, Relyvrio (when relevant), and newer ALS agents?

Riluzole is the earliest cornerstone among oral ALS disease-modifying options, used broadly even when patients receive later-line or add-on therapies.

Comparative positioning

• Versus edaravone: riluzole is oral and is typically used as ongoing baseline therapy; edaravone’s historical role is acute/short-course infusion patterns (practice varies by payer and eligibility).
• Versus newer disease-modifying agents: newer ALS therapies compete at the margin by offering additional benefit in specific populations, but riluzole often remains part of standard-of-care background therapy.

Practical implication for market analysis

Newer entrants usually do not fully replace riluzole because many ALS treatment algorithms keep it in place as baseline care, leaving riluzole’s market resilient but price-sensitive.

What is the Orange Book status of riluzole in the US?

Riluzole is an approved small-molecule drug with multiple generic versions. For investors and legal teams, the key diligence is not just the active ingredient patent coverage, but the presence of:

• Approved product-specific patents
• Method-of-use patents tied to ALS indications
• Exclusivity blocks that may impact generic entry timing

What kinds of patents are typically listed for riluzole products?

Orange Book listings for established generics often include:

• Formulation and process patents (manufacturing method, polymorph, formulation)
• Method-of-use patents (indication-specific use in ALS)
• Composition-of-matter patents are usually older and may be expired or near-expiration for the active ingredient

What patents protect riluzole and when do they expire?

Riluzole is a legacy molecule with an established patent history dating back to original development. For a current market projection, what matters is whether any remaining:

• Formulation/process patents are still enforceable
• Method-of-use patents still have active life that could block generic entry or trigger settlements

How to interpret remaining patent risk for riluzole

For a mature drug:

• The most relevant risk to new entrants is product-specific patent coverage on particular strengths, dosage forms, or manufacturing variants.
• The strongest litigation exposure typically correlates with recently listed patents or late-cycle Orange Book additions, not with the core active ingredient molecule.

What Paragraph IV challenges exist for riluzole generics?

Paragraph IV filing activity for riluzole historically clusters around product entries and patent carve-outs rather than new therapeutic coverage. In the current cycle, the most business-relevant considerations are:

• Whether any Paragraph IV suits remain active for particular generic companies or particular strengths
• Whether settlements create delayed launch windows for subsequent competitors

Competitive entry risk for new riluzole generics

Market risk for entrants usually comes from:

• The possibility that an Orange Book patent not expected by the applicant is still asserted
• Settlement terms that cap market access for a defined time
• Launch timing constraints driven by manufacturing validation and regulatory interchangeability

What current riluzole patent litigation affects market access?

Riluzole litigation, where present, typically involves:

• Patent infringement claims on formulation/process or method-of-use listings
• Accelerated dismissal or settlement that resolves a narrow set of product claims

How litigation translates to commercial outcomes

• If a settlement delays a launch, it creates temporary pricing support and share gains for existing suppliers.
• If cases are dismissed early, generic competition proceeds, suppressing net price.

Which companies sell riluzole and what does the competitive landscape look like?

The riluzole market is usually shared among multiple generic manufacturers and, historically, the branded originator legacy product.

Competitive dynamics in generic riluzole

Key differentiators:

• Lowest net cost through contracting
• Supply reliability and production scale
• Ability to meet shelf-life and distribution requirements
• Dosing form consistency and line extensions if used by payers

Business consequence for projections

As more generic entrants establish contracts, net price tends to decline; however, stable treated volume can offset part of the revenue erosion.

What are the regulatory milestones for riluzole right now?

Riluzole’s current regulatory state supports:

• Ongoing generic approvals through ANDA pathways
• Label maintenance consistent with ALS standard-of-care guidance
• Safety monitoring guidance, especially hepatotoxicity and liver enzyme monitoring

Does riluzole have any new FDA milestones?

For an older molecule, near-term FDA milestones usually relate to:

• New generic product approvals
• Patent certification changes on existing products
• Labeling updates based on safety communications rather than new effectiveness changes

How should investors and BD teams use clinical trial updates for riluzole?

Clinical trial updates for riluzole are most actionable in combination-development strategies and real-world evidence planning.

Commercially actionable signals

• Evidence that riluzole background therapy affects outcome separation in combination trials can shape inclusion criteria for new studies.
• Safety tolerability data in real-world cohorts influences switching risk from other baseline therapies.

BD and licensing angle

Riluzole itself is not a typical licensing target for new development. The licensing angle is more frequently:

• Positioning riluzole as part of a combination regimen in proprietary development programs
• Using trial and biomarker evidence to justify combination claims

Key takeaways

• Riluzole clinical updates in 2024–2026 are mainly combination- and real-world oriented, not new riluzole monotherapy registrational programs.
• Market growth is constrained by mature generic competition, with net revenue expected to be flat-to-decline while unit volume may hold or rise modestly.
• The most important commercial and legal risk for riluzole is product-specific Orange Book patent coverage and any residual litigation that can delay generic launches, rather than active ingredient patent life.
• Clinical trial evidence is best used to inform combination strategy, trial design for add-on therapies, and guideline positioning.

FAQs

1) Does riluzole improve survival in ALS compared with placebo in recent analyses?
Recent trials and meta-analytic work continue to support riluzole’s modest benefit profile relative to placebo, but the magnitude is incremental and used as baseline standard-of-care in most modern combination studies.

2) What is the usual dosing and formulation landscape for riluzole generics?
Riluzole is primarily sold as oral tablets with multiple generic strengths; the commercial focus is on bioequivalence, stability, and manufacturing consistency across suppliers.

3) How does riluzole safety management affect adherence in practice?
Liver enzyme monitoring and GI or general tolerability influence persistence; adherence tends to be better where hepatotoxicity monitoring workflows are standardized in ALS clinics.

4) Are there biosimilar or biologic alternatives that replace riluzole?
No biosimilar substitute exists for riluzole because it is a small molecule. New biologics or other small molecules may add to care, but they usually do not eliminate riluzole’s backbone role.

5) What should procurement teams watch for in riluzole supply?
Contracting changes, manufacturing capacity, and any launch delays tied to Orange Book patent resolutions are the most direct drivers of realized net pricing and availability.

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References

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