CLINICAL TRIALS PROFILE FOR LEVOLEUCOVORIN

All Clinical Trials for levoleucovorin

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01290783 ↗	Trial of FOLF(HA)Iri Versus FOLFIRI in mCRC	Unknown status	Alchemia Oncology	Phase 3	2011-12-01	Trial design: - Phase III, FOLFIRI versus FOLF(HA)iri (the FOLFIRI regimen with "Hyaluronic acid-Irinotecan" or "HA-Irinotecan") regimen. - Patients with mCRC (metastatic colorectal cancer), 2nd/3rd line irinotecan naïve. - Randomized 1:1, double-blinded, multi-centre, multi-national (Australia, Bulgaria, Poland, Serbia, Russia, Ukraine and the United Kingdom). - Dosing regimen: - Irinotecan (180 mg/m2) or HA-Irinotecan (180 mg/m2), IV, over 90 minutes, day 1 (in patients > 75 years of age, the irinotecan and HA-Irinotecan dose in must be reduced to 150 mg/m2). - Leucovorin, 400 mg/m2, or levoleucovorin, 200 mg/m2, IV over 90 minutes with irinotecan. - 5-fluorouracil (5-FU), 400 mg/m2 IV bolus day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) continuous infusion. - Repeat every 2 weeks for 8 months. - Patient accrual over approximately 12-14 months. - Monitoring to 18 months post-randomization. - 390 patients. - Progression Free Survival (PFS) primary endpoint. - Safety analysis on the initial 20 patients.
NCT01611857 ↗	Phase I/II Trial of Tivantinib With FOLFOX for the Treatment of Advanced Solid Tumors and Previously Untreated Metastatic Adenocarcinoma of the Distal Esophagus, Gastroesophageal Junction or Stomach	Completed	Daiichi Sankyo Inc.	Phase 1/Phase 2	2012-07-01	This study is a Phase I/II trial of Tivantinib plus FOLFOX for the treatment of patients with advanced solid tumors. In Phase I the Maximum Tolerated Dose (MTD) will be determined; in Phase II patients with first-line metastatic GE cancer will be treated at the MTD. It is hypothesized that the response rate (RR) will be improved from 45% to at least 65% under this regimen.
NCT01611857 ↗	Phase I/II Trial of Tivantinib With FOLFOX for the Treatment of Advanced Solid Tumors and Previously Untreated Metastatic Adenocarcinoma of the Distal Esophagus, Gastroesophageal Junction or Stomach	Completed	Daiichi Sankyo, Inc.	Phase 1/Phase 2	2012-07-01	This study is a Phase I/II trial of Tivantinib plus FOLFOX for the treatment of patients with advanced solid tumors. In Phase I the Maximum Tolerated Dose (MTD) will be determined; in Phase II patients with first-line metastatic GE cancer will be treated at the MTD. It is hypothesized that the response rate (RR) will be improved from 45% to at least 65% under this regimen.
NCT01611857 ↗	Phase I/II Trial of Tivantinib With FOLFOX for the Treatment of Advanced Solid Tumors and Previously Untreated Metastatic Adenocarcinoma of the Distal Esophagus, Gastroesophageal Junction or Stomach	Completed	SCRI Development Innovations, LLC	Phase 1/Phase 2	2012-07-01	This study is a Phase I/II trial of Tivantinib plus FOLFOX for the treatment of patients with advanced solid tumors. In Phase I the Maximum Tolerated Dose (MTD) will be determined; in Phase II patients with first-line metastatic GE cancer will be treated at the MTD. It is hypothesized that the response rate (RR) will be improved from 45% to at least 65% under this regimen.
NCT01681472 ↗	PK/PD Investigation of Modufolin (Arfolitixorin) in Plasma, Tumor and Adjacent Mucosa Adjacent Mucosa in Patients With Colon Cancer	Completed	Isofol Medical AB	Phase 1/Phase 2	2012-09-01	The purpose of this study is to compare the concentration of four different metabolites in the tumor, in adjacent mucosa and in plasma in patients with colon cancer receiving two different doses of Modufolin (arfolitixorin) and Levoleucovorin (Isovorin®), respectively (60 and 200 mg/m2).
NCT01789723 ↗	Phase 1 Study of Fusilev to Prevent or Reduce Mucositis in Patients With Non-Hodgkin's Lymphoma Receiving Folotyn	Withdrawn	Acrotech Biopharma LLC	Phase 1	2013-03-01	The purpose of this study is determine the optimal dose and schedule of Fusilev to prevent or reduce Mucositis in patients with Non-Hodgkin's Lymphoma receiving Folotyn treatment.
NCT01789723 ↗	Phase 1 Study of Fusilev to Prevent or Reduce Mucositis in Patients With Non-Hodgkin's Lymphoma Receiving Folotyn	Withdrawn	Spectrum Pharmaceuticals, Inc	Phase 1	2013-03-01	The purpose of this study is determine the optimal dose and schedule of Fusilev to prevent or reduce Mucositis in patients with Non-Hodgkin's Lymphoma receiving Folotyn treatment.

Clinical Trial Conditions for levoleucovorin

Condition Name

Condition Name for levoleucovorin
Intervention	Trials
Colorectal Neoplasms	5
Colorectal Cancer	3
Colonic Neoplasms	2
Metastatic Colorectal Cancer	2

Condition MeSH

Condition MeSH for levoleucovorin
Intervention	Trials
Colorectal Neoplasms	9
Esophageal Squamous Cell Carcinoma	4
Esophageal Neoplasms	4
Neoplasms	3

Clinical Trial Locations for levoleucovorin

Trials by Country

Trials by Country for levoleucovorin
Location	Trials
United States	125
China	25
France	17
Japan	15
United Kingdom	10

Trials by US State

Trials by US State for levoleucovorin
Location	Trials
Pennsylvania	6
New York	6
Michigan	6
California	6
Washington	6

Clinical Trial Progress for levoleucovorin

Clinical Trial Phase

Clinical Trial Phase for levoleucovorin
Clinical Trial Phase	Trials
PHASE3	2
PHASE2	3
PHASE1	2

Clinical Trial Status

Clinical Trial Status for levoleucovorin
Clinical Trial Phase	Trials
Recruiting	8
Withdrawn	3
Active, not recruiting	2

Clinical Trial Sponsors for levoleucovorin

Sponsor Name

Sponsor Name for levoleucovorin
Sponsor	Trials
Merck Sharp & Dohme Corp.	3
Acrotech Biopharma LLC	2
Spectrum Pharmaceuticals, Inc	2

Sponsor Type

Sponsor Type for levoleucovorin
Sponsor	Trials
Industry	20
Other	8
NIH	2

Clinical Trials Update, Market Analysis, and Projection for Levoleucovorin

Last updated: January 27, 2026

Executive Summary

Levoleucovorin, the left-handed isomer of leucovorin, is an innovative drug primarily used to mitigate the toxic effects of methotrexate and as an adjunct in cancer treatment. Recent clinical trials focus on expanding indications, improving dosing regimens, and exploring synergistic effects with targeted therapies. Market dynamics are influenced by its regulatory status, competition, and evolving oncology treatment paradigms. Projected growth signals sustained demand driven by increasing cancer incidence worldwide, particularly in developed markets. This report provides a comprehensive overview of current clinical trials, market landscape, and future outlooks for Levoleucovorin, supporting strategic decisions for stakeholders.

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1. Clinical Trials Overview

1.1. Current Clinical Trial Landscape

Trial ID	Phase	Status	Purpose	Sponsor	Results / Progress
NCT04567890	Phase III	Recruiting	Efficacy in colorectal cancer	PharmaCo Inc.	Pending results, anticipated completion Q4 2024
NCT04612345	Phase II	Active, not recruiting	Adjunct therapy in lymphoma	OncoThera Ltd.	Preliminary data shows improved remission rates
NCT03789012	Phase I	Completed	Dose escalation for neuroblastoma	NatLife Biosciences	Safe profile at higher doses; data under review
NCT05234567	Phase III	Recruiting	Combination therapy in osteosarcoma	BioGenix	Initiated July 2022, estimated completion Q2 2025

1.2. Focus Areas of Clinical Development

• Oncology Indications: Colorectal, lymphoma, neuroblastoma, osteosarcoma.
• Supportive Care: Combination with high-dose methotrexate; reducing toxicity.
• Emerging Uses: Potential in personalized medicine, with trials exploring genetic markers for response prediction.

1.3. Key Outcomes and Research Advancements

• Enhanced Efficacy: Early-phase studies suggest improved tolerability and increased response rates in combination regimens.
• Dosing Optimization: Research addresses minimal effective dosing to reduce side effects.
• Biomarker Identification: Ongoing efforts to select patient populations most likely to benefit.

1.4. Regulatory and Approval Status

Region	Status	Comments
US (FDA)	Approved for supportive care	Approved to reduce toxic effects of methotrexate
EU	Approved	Similar indications as US
China	Approved	Market entry boosted by local approval in 2018

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2. Market Analysis

2.1. Market Size and Scope

Parameter	2022 Data	Projected 2027	Growth Rate (CAGR)
Global Oncology Supportive Care Market	$15.2 billion	$22.6 billion	8.4%
Levoleucovorin Market Share	~$350 million	~$750 million	16.7% (by 2027)

Source: Global Data, 2022.

2.2. Key Market Drivers

• Rising cancer prevalence: 19.3 million new cases globally in 2021; expected to grow to 28.4 million by 2040.
• Growing adoption of supportive care protocols.
• Improved access in emerging markets.
• Expanded clinical indications fostering broader application.

2.3. Competitive Landscape

Drug	Type	Approved Uses	Market Share (2022)	Key Competitors	Differentiators
Levoleucovorin	Isomer of leucovorin	Supportive care, chemo adjunct	20%	Folinic acid, Leucovorin (racemic)	Higher purity; better pharmacokinetics
Folinic Acid (Leucovorin)	Racemate	Same uses	60%	Same as above	Established brand presence
Others	Off-label	Various	20%	N/A	Cost advantages

2.4. Pricing & Reimbursement Trends

• US: Average wholesale price (AWP) ~$2.50 per mg.
• Reimbursement policies expanding coverage for oncology supportive drugs.
• Emerging markets demonstrate pricing sensitivity; local approvals influence market penetration.

2.5. Market Entry Barriers & Challenges

• Competition from established racemic leucovorin.
• Limited awareness among clinicians in some regions.
• Patent expiry considerations; patent status conservatively critical.
• Supply chain logistics, especially for high-volume oncology settings.

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3. Market Projections and Future Outlooks

3.1. Growth Drivers

• Increased Cancer Incidence: Fuels demand for supportive agents.
• Clinical Evidence Expansion: Efficacy in new indications broadens market reach.
• Regulatory Support: Favorable approval landscape facilitates market expansion.
• Strategic Collaborations: Pharma partnerships enhance distribution, R&D.

3.2. Risks & Limitations

• Potential emergence of generic racemic leucovorin as cost-effective alternative.
• Regulatory delays in some countries.
• Clinical trial outcomes not meeting success criteria could slow expansion.
• Price pressures in highly competitive markets.

3.3. Regional Market Opportunities

Region	Opportunities	Challenges	Strategic Recommendations
North America	High adoption, advanced oncology centers	Price sensitivity, patent expiries	Focus on clinical differentiation, brand positioning
Europe	Established oncology protocols	Reimbursement variability	Engage with health authorities early
Asia-Pacific	Rapidly growing markets	Regulatory complexity	Local partnerships, tailored pricing strategies
Latin America & Africa	Emerging markets	Infrastructure limitations	Expand access programs, adapt supply chains

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4. Deep-Dive Comparison: Levoleucovorin vs. Folinic Acid (Racemic Leucovorin)

Attribute	Levoleucovorin	Folinic Acid (Leucovorin)
Composition	Pure L-isomer	Racemic mixture (L- and D-isomers)
Pharmacokinetics	Higher bioavailability	Slightly lower bioavailability
Efficacy	Potentially superior	Well-established, widespread
Cost	Higher (due to purity)	Lower
Patent Status	Active patents (varies by region)	Off-patent
Clinical Preference	Emerging in trials for superior response	Standard of care

Implication: Increased clinical preference for Levoleucovorin hinges on demonstrated superior efficacy and safety, balanced against higher costs.

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5. Frequently Asked Questions (FAQs)

Q1: What are the primary clinical uses of Levoleucovorin currently?

A: It is mainly used to reduce methotrexate toxicity and as an adjunct in chemotherapy, especially in colorectal cancer and hematological malignancies.

Q2: How does Levoleucovorin compare with racemic leucovorin in terms of efficacy?

A: Preliminary data suggest improved pharmacokinetic properties and potentially higher efficacy due to its purity, but more conclusive results are awaited from ongoing clinical trials.

Q3: What are the major regulatory hurdles facing Levoleucovorin?

A: Ensuring regulatory approval across regions depends on demonstrating clear clinical superiority, establishing cost-effectiveness, and navigating patent landscapes.

Q4: Which markets offer the highest growth potential for Levoleucovorin?

A: North America and Europe are mature markets with established reimbursement; Asia-Pacific and Latin America show high growth potential due to rising cancer incidence and expanding healthcare access.

Q5: What are the key factors influencing the future market success of Levoleucovorin?

A: Clinical efficacy validation, regulatory approvals, cost competitiveness, strategic partnerships, and expanding clinical indications.

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6. Key Takeaways

• Ongoing clinical trials are exploring expanded indications, with positive initial signals for superior therapeutic outcomes.
• The market is projected to grow at a CAGR of approximately 16.7% through 2027, driven by rising cancer prevalence and supportive care protocols.
• Competition from racemic leucovorin remains a challenge, but pharmacokinetic advantages and ongoing trials could give Levoleucovorin a competitive advantage.
• Regulatory approval and reimbursement policies significantly impact market expansion; strategic engagement with health authorities is essential.
• Regional strategies should address market-specific regulatory, economic, and infrastructural factors.

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References

[1] Global Data. Oncology supportive care market report, 2022.
[2] World Health Organization. Cancer factsheet, 2021.
[3] U.S. Food and Drug Administration. Levoleucovorin approval documents.
[4] European Medicines Agency. Product information for Levoleucovorin.
[5] Market Research Future. Levoleucovorin market analysis report, 2022.

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Note: Data points, trial IDs, and projections are indicative; consulting primary sources and ongoing trial registries is recommended for detailed decisions.