CLINICAL TRIALS PROFILE FOR METHOTREXATE SODIUM

All Clinical Trials for methotrexate sodium

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00001863 ↗	Leflunomide to Treat Uveitis	Completed	National Eye Institute (NEI)	Phase 2	1999-03-01	This study will investigate the safety and effectiveness of the drug Leflunomide to treat uveitis-an inflammation of the eye caused by an immune system abnormality. Leflunomide suppresses immune system activity and has been shown to control autoimmune diseases, such as arthritis (joint inflammation), in animals. It has also improved symptoms in patients with rheumatoid arthritis, and the Food and Drug Administration has approved it for treating patients with this disease. Eye and joint inflammation may have similar causes, and medicines for arthritis often help patients with eye inflammation. This study will examine whether Leflunomide can help patients with uveitis. Patients with uveitis who are not responding well to steroid treatment and patients who have side effects from other medicines used to treat uveitis (such as cyclosporine, cyclophosphamide, methotrexate or azathioprine) or have refused treatment because of possible side effects of these medicines may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood test and eye examination. The eye exam includes a check of vision and eye pressure, examination of the back of the eye (retina) with an ophthalmoscope and the front of the eye with a microscope. They will also undergo a procedure called fluorescein angiography to look at the blood vessels of the eye. A dye called sodium fluorescein is injected into the bloodstream through a vein. After the dye reaches the blood vessels of the eye, photographs are taken of the retina. Study participants will be divided into two groups. One group will take 100 milligrams of Leflunomide once a day for 3 days and then 20 milligrams once a day for 6 months. The other group will take a placebo-a pill that looks like the Leflunomide pill but does not contain the medicine. All patients in both groups will also take prednisone. Patients will have follow-up examinations at weeks 1, 4, 8, 12, 16, and 24 (6 months) of the study. Each follow-up visit will include a repeat of the screening exams and an evaluation of side effects or discomfort from the medicine. Those who do well and want to continue their assigned treatment after 6 months can continue that treatment for another 6 months and will have follow-up exams at months 9 and 12.
NCT00006184 ↗	Chemotherapy, Stem Cell Transplantation and Donor and Patient Vaccination for Treatment of Multiple Myeloma	Completed	National Cancer Institute (NCI)	Phase 2	2001-02-08	Background: The mainstay of therapy for newly diagnosed multiple myeloma patients remains systemic chemotherapy. Although partial remissions of up to 60% are obtained with conventional regimens, multiple myeloma is essentially an incurable disease with a median survival of approximately 30 months. Allogeneic stem cell transplantation (SCT) results in a high percentage of complete remissions, but it can be associated with significant treatment-related mortality, which has been primarily attributed to conventional myeloablative transplant regimens. Recent clinical studies have shown that highly immunosuppressive yet non-myeloablative doses of fludarabine-based chemotherapy can result in alloengraftment. Even with a reduction in treatment related mortality, success with allogeneic SCT is limited by a significant risk of relapse. Donor immunization with myeloma Id in the setting of a non-myeloablative allogeneic SCT may represent a novel strategy for the treatment of multiple myeloma. Objectives: Primary Objectives: To induce cellular and humoral immunity in allogeneic stem cell donors and recipients against the unique idiotype expressed by the recipient's myeloma. To determine whether antigen-specific immunity, induced in the stem cell donor, can be passively transferred to the allogeneic SCT recipient in the setting of a non-myeloablative conditioning regimen. Secondary Objectives: To evaluate the effect of the Fludarabine-(etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide) EPOCH regimen on host T cell depletion and myeloid depletion prior to allogeneic SCT. To determine the efficacy of a novel conventional chemotherapy regimen (Fludarabine-EPOCH) in the setting multiple myeloma. To determine the treatment-related morbidity and mortality of allogeneic stem cell transplantation using a non-myeloablative conditioning regimen in multiple myeloma. To determine if the re-vaccination of allogeneic stem cell donors with the unique idiotype expressed by the recipient's myeloma will enhance cellular and humoral immunity to patient specific-idiotype prior to lymphocyte donation for the treatment of patients with recurrent or progressive disease after transplantation. Eligibility: Patients 18-75 years of age with Immunoglobulin G (IgG) or Immunoglobulin A (IgA) multiple myeloma. Patients must have achieved at least a partial remission following initial conventional chemotherapy regimen or after autologous stem cell transplantation. Consenting first degree relative matched at 6/6 or 5/6 human leukocyte antigen (HLA) antigens. Design: Phase 2 trial using a non-myeloablative conditioning regimen to reduce treatment-related toxicity. Recipient will undergo a plasmapheresis to obtain starting material for the isolation of idiotype protein. Donors would be immunized with an Id vaccine prepared from the patient. Prior to transplantation patients would receive a conventional chemotherapy regimen which contains agents active in myeloma and is T cell depleting. The allogeneic SCT would be performed with a conditioning regimen consisting of cyclophosphamide and fludarabine. The stem cell source would be blood mobilized with filgrastim. Recipients will be immunized with the Id vaccine following transplantation.
NCT00045305 ↗	Reduced-Intensity Regimen Before Donor Bone Marrow Transplant in Treating Patients With Myelodysplastic Syndromes	Completed	National Cancer Institute (NCI)	Phase 2	2005-05-01	RATIONALE: Photopheresis treats the patient's blood with drugs and ultraviolet light outside the body and kills the white blood cells. Giving photopheresis, pentostatin, and radiation therapy before a donor bone marrow or stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving pentostatin before transplant and cyclosporine or mycophenolate mofetil after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving pentostatin together with photopheresis and total-body irradiation work before donor bone marrow transplant in treating patients with myelodysplastic syndromes.
NCT00045305 ↗	Reduced-Intensity Regimen Before Donor Bone Marrow Transplant in Treating Patients With Myelodysplastic Syndromes	Completed	Eastern Cooperative Oncology Group	Phase 2	2005-05-01	RATIONALE: Photopheresis treats the patient's blood with drugs and ultraviolet light outside the body and kills the white blood cells. Giving photopheresis, pentostatin, and radiation therapy before a donor bone marrow or stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving pentostatin before transplant and cyclosporine or mycophenolate mofetil after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving pentostatin together with photopheresis and total-body irradiation work before donor bone marrow transplant in treating patients with myelodysplastic syndromes.
NCT00074165 ↗	Treating Patients With Recurrent PCNSL With Carboplatin/BBBD and Adding Rituxan To The Treatment Regimen	Terminated	National Cancer Institute (NCI)	Phase 2	2003-01-01	RATIONALE: Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as carboplatin, cyclophosphamide, etoposide, etoposide phosphate, and cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Osmotic blood-brain barrier disruption uses certain drugs to open the blood vessels around the brain and allow anticancer substances to be delivered directly to the brain tumor. Chemoprotective drugs such as sodium thiosulfate may protect normal cells from the side effects of carboplatin-based chemotherapy. Combining rituximab with chemotherapy given with osmotic blood-brain barrier disruption plus sodium thiosulfate may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining rituximab with combination chemotherapy given with osmotic blood-brain barrier disruption plus sodium thiosulfate in treating patients who have refractory or recurrent primary CNS lymphoma.
NCT00074165 ↗	Treating Patients With Recurrent PCNSL With Carboplatin/BBBD and Adding Rituxan To The Treatment Regimen	Terminated	OHSU Knight Cancer Institute	Phase 2	2003-01-01	RATIONALE: Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as carboplatin, cyclophosphamide, etoposide, etoposide phosphate, and cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Osmotic blood-brain barrier disruption uses certain drugs to open the blood vessels around the brain and allow anticancer substances to be delivered directly to the brain tumor. Chemoprotective drugs such as sodium thiosulfate may protect normal cells from the side effects of carboplatin-based chemotherapy. Combining rituximab with chemotherapy given with osmotic blood-brain barrier disruption plus sodium thiosulfate may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining rituximab with combination chemotherapy given with osmotic blood-brain barrier disruption plus sodium thiosulfate in treating patients who have refractory or recurrent primary CNS lymphoma.

Clinical Trial Conditions for methotrexate sodium

Condition Name

Condition Name for methotrexate sodium
Intervention	Trials
Leukemia	4
Acute Lymphoblastic Leukemia	4
Lymphoma	3
B Acute Lymphoblastic Leukemia	3

Condition MeSH

Condition MeSH for methotrexate sodium
Intervention	Trials
Leukemia	16
Precursor Cell Lymphoblastic Leukemia-Lymphoma	14
Leukemia, Lymphoid	13
Lymphoma	7

Clinical Trial Locations for methotrexate sodium

Trials by Country

Trials by Country for methotrexate sodium
Location	Trials
United States	319
Canada	29
Australia	13
Korea, Republic of	4
China	4

Trials by US State

Trials by US State for methotrexate sodium
Location	Trials
Ohio	15
Minnesota	13
Florida	13
Maryland	12
Michigan	12

Clinical Trial Progress for methotrexate sodium

Clinical Trial Phase

Clinical Trial Phase for methotrexate sodium
Clinical Trial Phase	Trials
PHASE4	3
PHASE2	2
Phase 4	2

Clinical Trial Status

Clinical Trial Status for methotrexate sodium
Clinical Trial Phase	Trials
Completed	14
Recruiting	8
Terminated	6

Clinical Trial Sponsors for methotrexate sodium

Sponsor Name

Sponsor Name for methotrexate sodium
Sponsor	Trials
National Cancer Institute (NCI)	13
Therapeutic Advances in Childhood Leukemia Consortium	5
OHSU Knight Cancer Institute	4

Sponsor Type

Sponsor Type for methotrexate sodium
Sponsor	Trials
Other	49
NIH	16
Industry	10

Last updated: July 27, 2026

Methotrexate Sodium Clinical Trials Update, Market Outlook, and Revenue Projection (2026–2036)

Methotrexate sodium remains a long-cycle, low-cost anchor in inflammatory disease and oncology-adjacent regimens. Clinical activity is concentrated in label-expansion, biologic-sparing strategies, subpopulation outcomes (including pregnancy-related safety and comorbidity), and delivery optimization rather than new mechanism discovery. Market growth is forecast to track chronic-care penetration, evolving guideline adherence, and ongoing uptake in lower-resource settings where methotrexate’s affordability is decisive. Pricing pressure stays the primary downside risk; the upside risk comes from new-use expansions and improved adherence via less frequent or better tolerated formulations.

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What is the current clinical trial landscape for methotrexate sodium?

Which trial phases are active and what are the common endpoints?

Active development programs for methotrexate sodium typically cluster into three buckets:

1. Comparative tolerability and adherence trials

   • Endpoints: discontinuation rates, GI intolerance, fatigue, lab discontinuation due to liver/hematologic toxicity, and patient-reported outcomes.
   • Common design: randomized open-label comparator trials across oral dosing strategies and route switching (oral vs subcutaneous).

2. Dose optimization and “treatment target” trials

   • Endpoints: proportion achieving ACR responses (rheumatology), minimal disease activity/remission targets, time to flare, and steroid-sparing.

3. Safety-focused trials and special populations

   • Endpoints: hepatic enzyme trends under monitoring protocols, hematologic toxicity incidence, infection rates in comorbid cohorts, and pregnancy exposure frameworks.

What trial topics dominate by therapeutic area?

• Rheumatoid arthritis (RA): methotrexate is the baseline csDMARD in most algorithmic pathways. Current trial energy is directed at switching strategies (route and dosing), combination timing with biologics/JAK inhibitors, and minimizing adverse-event withdrawals.
• Psoriatic arthritis (PsA): focus is on comparative effectiveness and tolerability, often as background therapy in combination regimens.
• Inflammatory bowel disease (IBD): methotrexate is used in select lines where conventional therapy fails or is contraindicated; recent studies target steroid-sparing and remission durability.
• Oncology-adjacent use: methotrexate sodium remains relevant in combination regimens; trials increasingly pursue supportive care, rescue protocols, and toxicology risk mitigation rather than mechanism novelty.

What is the most likely direction of change in the trial pipeline?

The pipeline trend is toward incremental improvements that reduce discontinuation and lab monitoring burden while preserving efficacy. Trials that can credibly support guideline positioning for route switching, combination ordering, or lower discontinuation profiles have the best probability of translation into uptake.

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How does methotrexate sodium compare with other csDMARDs and biologics in clinical outcomes?

What is the efficacy-efficiency profile versus alternatives?

Methotrexate sodium generally underperforms newer targeted therapies on maximal efficacy in difficult-to-treat populations but wins on:

• high likelihood of achieving clinically meaningful responses when used early
• cost and access advantages
• long-established manageability with monitoring frameworks

How do outcomes differ when switching oral to subcutaneous?

The clinical pattern seen across multiple study types is:

• fewer GI adverse effects and improved tolerability with subcutaneous administration in patients with oral intolerance or inadequate response
• improved adherence due to fewer dose disruptions
• comparable efficacy when pharmacokinetics stabilize

What is the practical implication for trial readouts?

Trials that stratify by baseline tolerability and previous response often show that route switching converts “non-response due to intolerance” into “response due to exposure optimization.”

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Which drug forms and regimens for methotrexate sodium are most active in development?

Oral tablet vs injectable: where do trials concentrate?

• Oral dosing optimization trials focus on timing strategies, dose escalation cadence, and supportive regimens to manage mucositis and GI effects.
• Subcutaneous injection trials focus on conversion protocols, injection training, and adherence.

Folic acid co-therapy

Across most contemporary protocols, folic or folinic acid rescue is standard. Trial endpoints typically measure:

• adverse event incidence reduction
• discontinuation rates
• hematologic toxicity patterns under folate rescue

What does “delivery optimization” mean for methotrexate in 2026?

Delivery optimization typically means:

• route switching protocols
• adherence tools
• simplified titration and monitoring cadence
• supportive care alignment (antiemetics, folate rescue adherence)

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What patents protect methotrexate sodium clinical use, formulations, and manufacturing?

Why patent activity matters for a legacy generic

Methotrexate sodium is largely generic in major markets. The practical IP risk is less about “composition of matter” and more about:

• branded formulation patents tied to specific excipients, release behavior, or device-related injection delivery systems
• method-of-use patents related to dosing strategies, monitoring approaches, or combination ordering
• manufacturing and stability improvements for specific presentation forms

Key patent estate dynamics

Because the core molecule is off-patent in most jurisdictions, competitive positioning often depends on:

• proprietary formats (injectable devices, prefilled syringes, stability profiles)
• label-specific method-of-use coverage (route switching, combination timing)
• exclusivity tied to specific regulatory dossiers and presentation strengths

What this means for market power

Market power is limited for true generics. It concentrates around:

• supply reliability
• contract pricing
• channel agreements with health systems
• product differentiation in injection devices or managed-care preferencing

(For a litigation-grade patent map with specific publication numbers and assignees, the dataset must be pulled from jurisdictional patent registers and FDA Orange Book. This request does not include a jurisdiction scope, strength, dosage form, or product list.)

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When does methotrexate sodium lose exclusivity in major markets?

Methotrexate sodium’s core exclusivity has long expired in the US and EU for most presentations. Current “exclusivity” is typically presentation-specific (data exclusivity, regulatory exclusivity for particular formulations or delivery systems, and any remaining branded lifecycle protections where relevant).

A reliable exclusivity timetable requires:

• identifying the exact marketed product(s) by strength and dosage form (oral vs subcutaneous vs preservative-free formats)
• mapping those SKUs to FDA Orange Book listings and jurisdictional exclusivity records

(Without that product-level mapping, an expiration timeline would be incomplete.)

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What is the Orange Book status of methotrexate sodium?

Orange Book status: what you should expect structurally

For a legacy csDMARD like methotrexate sodium, Orange Book listings usually show:

• multiple abbreviated new drug approvals (ANDAs)
• a small number of formulation/device-related listings (for specific injection presentations)
• discontinuation of any remaining branded exclusivity coverage except for niche presentations

Actionable market interpretation

• If a product is fully generic, near-term market entry risk is low because supply is already established.
• If a presentation has a limited number of holders, price competition can lag and procurement schedules can sustain premium contracts.

(Accurate Orange Book status requires listing-level retrieval by drug name, dosage form, and strength.)

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How much of the methotrexate sodium market is in US vs Europe vs emerging markets?

Market structure

Methotrexate sodium demand is distributed across:

• high-income markets: stable chronic-care volume, driven by RA, PsA, and guideline-aligned initiation patterns
• Europe: similar disease mix with different prescribing habits and reimbursement levers
• emerging markets: high volume sensitivity to price and supply continuity

Commercial reality

The dominant drivers are:

• clinical guideline adherence and treatment algorithms
• payer formularies and step-therapy placement
• supply and procurement reliability

Because the drug is low-cost, revenue growth is limited by:

• strong generic competition
• periodic price cuts
• tender-based procurement

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What is the market forecast for methotrexate sodium through 2036?

Baseline revenue projection framework

A practical forecast for methotrexate sodium uses three inputs:

1. Volume: treated patient prevalence and initiation rates in RA/PsA/IBD algorithms.
2. Share: oral vs injectable mix shift driven by tolerability.
3. Net price: tender-driven price erosion and generics substitution speed.

Revenue outlook (directional)

• US: modest growth or flat-to-slight decline in net revenue driven by continued price pressure, offset by route-mix shifts and stable utilization.
• EU: similar trajectory, with reimbursement and tender dynamics shaping the net price trend.
• Emerging markets: more resilient growth in units, with revenue capped by procurement pricing.

Scenario view (what changes the shape of the curve)

• Upside scenario: sustained shift to subcutaneous in patients who fail oral due to tolerability plus guideline uptake of “optimize then escalate” strategies.
• Downside scenario: accelerated price compression from additional generic entrants or procurement policy changes that deepen substitution.

(Quantitative numeric forecasts require an identified product scope, geography, and unit/price basis. The request does not specify whether the projection should cover methotrexate sodium across all presentations globally or specific branded/generic cohorts.)

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How do clinical outcomes translate into commercial outcomes for methotrexate sodium?

Tolerability improvements drive adherence

Methotrexate discontinuation is the critical economic variable:

• fewer discontinuations increases persistence and long-run treated prevalence
• improved persistence reduces “jump to expensive alternatives” trajectories

Steroid-sparing and flare control influence payer decisions

Even with modest incremental efficacy, outcomes that reduce flare frequency or rescue steroid use can strengthen formulary positioning, especially in step-therapy environments.

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What generic entry risks exist for methotrexate sodium?

Where entry risk is real

• injectable presentations with device and stability differentiation can have fewer competitors
• preservative-free or special packaging SKUs can be more constrained

Where entry risk is low

• common oral tablet strengths and widely manufactured injection lines often have deep generic coverage

Business implication

Risk is less about “can a new generic enter” and more about:

• manufacturing capacity and compliance
• ability to win tenders and hospital formularies
• drug-device usability metrics for injection products

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What manufacturing and regulatory barriers affect supply and pricing?

Quality system complexity

As a long-established generic, methotrexate sodium is not usually limited by novel manufacturing science. Barriers are usually:

• stability and shelf-life management for injectable presentations
• sterility assurance for injection manufacturing
• batch consistency and impurity profiles that trigger regulatory scrutiny

Regulatory inspection and supply events

Price volatility can follow:

• manufacturing shutdowns
• recall events
• supply interruptions that trigger temporary procurement rationing

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Key competitors and competitive landscape for methotrexate sodium

Competitive dynamics

• In oral: competition is broad, pricing is tender-driven, and revenue is sensitive to market share changes during contract cycles.
• In injectable: competition can be less fragmented if device formats are more proprietary or if quality systems and supply chains reduce the number of qualified suppliers.

What to monitor

• new ANDA approvals for specific strengths and routes
• shortages or supply disruptions by major suppliers
• payer preferred positioning and switching policies (oral-to-injectable)

(Company-specific lists require product-level Orange Book and procurement data. This request does not specify the exact marketed methotrexate sodium product cohort.)

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Key Takeaways

• Methotrexate sodium clinical development is dominated by incremental trials aimed at tolerability, route switching, adherence, and safety in chronic inflammatory disease settings.
• Market outlook is likely stable with low-to-modest growth in net value given persistent generic price pressure; unit demand can remain supported by guideline-based csDMARD use and chronic prevalence.
• Commercial results hinge on persistence and discontinuation rates, with oral-to-subcutaneous shift being the most plausible lever for share improvement.
• Patent-driven market protection is limited at the molecule level; the actionable IP risk is presentation- and method-of-use-specific rather than composition-of-matter exclusivity.
• Quantitative market projections and SKU-specific timelines require an explicit product universe (dosage forms, strengths, geography, and holders).

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FAQs

1. What clinical endpoints matter most in methotrexate sodium trials for rheumatoid arthritis?
2. How does oral versus subcutaneous methotrexate sodium affect discontinuation and adherence rates?
3. Which methotrexate sodium presentations typically face the tightest supply constraints during shortages?
4. How do payer step-therapy policies influence methotrexate sodium market share versus biologics?
5. What monitoring protocols most strongly correlate with methotrexate sodium safety outcomes in real-world practice?

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References (APA)

1. FDA. (n.d.). Drug approvals and related documents (Orange Book and labeling resources). US Food and Drug Administration.
2. EULAR. (2022). Recommendations for the management of rheumatoid arthritis. European Alliance of Associations for Rheumatology.
3. ACR. (2021). Guideline for the treatment of rheumatoid arthritis. American College of Rheumatology.
4. EMA. (n.d.). Medicines (assessment reports and product information). European Medicines Agency.