CLINICAL TRIALS PROFILE FOR GLUCARPIDASE

All Clinical Trials for glucarpidase

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00018967 ↗	Carboxypeptidase-G2 in Treating Nervous System Toxic Effects in Patients Given an Overdose of Intrathecal Methotrexate	Completed	Children's Oncology Group	N/A	1993-11-01	RATIONALE: Chemoprotective drugs such as carboxypeptidase-G2 may protect normal cells from the toxic effects of chemotherapy. PURPOSE: Clinical trial to study the effectiveness of carboxypeptidase-G2 in treating nervous system toxic effects in patients given an accidental overdose of intrathecal methotrexate.
NCT00018967 ↗	Carboxypeptidase-G2 in Treating Nervous System Toxic Effects in Patients Given an Overdose of Intrathecal Methotrexate	Completed	National Cancer Institute (NCI)	N/A	1993-11-01	RATIONALE: Chemoprotective drugs such as carboxypeptidase-G2 may protect normal cells from the toxic effects of chemotherapy. PURPOSE: Clinical trial to study the effectiveness of carboxypeptidase-G2 in treating nervous system toxic effects in patients given an accidental overdose of intrathecal methotrexate.
NCT00219791 ↗	Study of Glucarpidase (CPG2) for the Management of Patients With Delayed Methotrexate Clearance	Completed	BTG International Inc.	Phase 2	2000-01-01	To evaluate the safety and efficacy of glucarpidase in patients with impaired methotrexate (MTX) clearance owing to MTX-induced renal failure following high-dose MTX therapy, or with intrathecal MTX overdose.
NCT00424645 ↗	Voraxaze for Delayed Methotrexate Clearance	Terminated	BTG International Inc.	Phase 1/Phase 2	2007-01-01	Primary Objectives: 1. To evaluate the efficacy of Glucarpidase (Voraxaze) in increasing the rate of methotrexate (MTX) clearance following high dose MTX treatment in patients with a delayed MTX clearance. 2. To evaluate the pharmacokinetics (PK) of Glucarpidase following high dose MTX treatment in patients with a delayed MTX clearance. 3. To evaluate the safety profile of Glucarpidase following high dose MTX treatment in patients with a delayed MTX clearance. Secondary Objectives: 1. To evaluate the effect of Glucarpidase on the incidence of neutropenic fever and use of intravenous (IV) antibiotics. 2. To evaluate the effect of Glucarpidase on the length of hospitalization. 3. To evaluate the effect of Glucarpidase on renal function. 4. To evaluate the effect of Glucarpidase on Quality of Life (QOL). 5. To evaluate the anti-glucarpidase antibody response. 6. To evaluate the efficacy of Glucarpidase following its use in repeated cycles of high dose MTX treatment.
NCT00424645 ↗	Voraxaze for Delayed Methotrexate Clearance	Terminated	M.D. Anderson Cancer Center	Phase 1/Phase 2	2007-01-01	Primary Objectives: 1. To evaluate the efficacy of Glucarpidase (Voraxaze) in increasing the rate of methotrexate (MTX) clearance following high dose MTX treatment in patients with a delayed MTX clearance. 2. To evaluate the pharmacokinetics (PK) of Glucarpidase following high dose MTX treatment in patients with a delayed MTX clearance. 3. To evaluate the safety profile of Glucarpidase following high dose MTX treatment in patients with a delayed MTX clearance. Secondary Objectives: 1. To evaluate the effect of Glucarpidase on the incidence of neutropenic fever and use of intravenous (IV) antibiotics. 2. To evaluate the effect of Glucarpidase on the length of hospitalization. 3. To evaluate the effect of Glucarpidase on renal function. 4. To evaluate the effect of Glucarpidase on Quality of Life (QOL). 5. To evaluate the anti-glucarpidase antibody response. 6. To evaluate the efficacy of Glucarpidase following its use in repeated cycles of high dose MTX treatment.
NCT00634322 ↗	High Dose Methotrexate With Leucovorin Rescue With or Without Glucarpidase in Osteosarcoma	Terminated	M.D. Anderson Cancer Center	Phase 2	2008-10-01	The purpose of this study is to demonstrate whether use of glucarpidase facilitates administration of the next cycle of chemotherapy as scheduled and improves safety and tolerability of HDMTX given with LV
NCT00634322 ↗	High Dose Methotrexate With Leucovorin Rescue With or Without Glucarpidase in Osteosarcoma	Terminated	BTG International Inc.	Phase 2	2008-10-01	The purpose of this study is to demonstrate whether use of glucarpidase facilitates administration of the next cycle of chemotherapy as scheduled and improves safety and tolerability of HDMTX given with LV

Clinical Trial Conditions for glucarpidase

Condition Name

Condition Name for glucarpidase
Intervention	Trials
Osteosarcoma	3
Lymphoma	2
Neurotoxicity	2
Diffuse Large B-Cell Lymphoma	1

Condition MeSH

Condition MeSH for glucarpidase
Intervention	Trials
Lymphoma	4
Osteosarcoma	3
Neurotoxicity Syndromes	2
Neoplasms	2

Clinical Trial Locations for glucarpidase

Trials by Country

Trials by Country for glucarpidase
Location	Trials
United States	49
Canada	7
United Kingdom	2
Australia	2
Denmark	1

Trials by US State

Trials by US State for glucarpidase
Location	Trials
New York	3
Pennsylvania	3
Oregon	2
New Jersey	2
Minnesota	2

Clinical Trial Progress for glucarpidase

Clinical Trial Phase

Clinical Trial Phase for glucarpidase
Clinical Trial Phase	Trials
Phase 3	1
Phase 2	5
Phase 1/Phase 2	2

Clinical Trial Status

Clinical Trial Status for glucarpidase
Clinical Trial Phase	Trials
Recruiting	4
Completed	4
Terminated	3

Clinical Trial Sponsors for glucarpidase

Sponsor Name

Sponsor Name for glucarpidase
Sponsor	Trials
BTG International Inc.	6
National Cancer Institute (NCI)	2
M.D. Anderson Cancer Center	2

Sponsor Type

Sponsor Type for glucarpidase
Sponsor	Trials
Other	25
NIH	2

Clinical Trials Update, Market Analysis, and Projection for Glucarpidase

Last updated: November 10, 2025

Introduction

Glucarpidase (trade name: Voraxaze) is an enzyme-based drug developed to mitigate high-dose methotrexate (HDMTX) toxicity by rapidly hydrolyzing methotrexate into inactive metabolites. It is primarily utilized in oncology to manage potentially lethal methotrexate toxicity, especially in cases where patients exhibit impaired renal clearance or experience delayed methotrexate elimination. Given the crucial clinical role of glucarpidase and evolving therapeutic landscapes, a comprehensive review of its clinical trials, market dynamics, and future projections reveals insights pertinent to stakeholders—including pharmaceutical companies, healthcare providers, and investors.

Clinical Trials Landscape

Current Status and Recent Developments

Glucarpidase has predominantly secured approval through the U.S. Food and Drug Administration (FDA) since 2012, under the orphan drug designation. Post-approval, ongoing clinical studies continue to explore its expanded applications, optimal dosing regimens, and safety profile.

• Continuing Investigations:
  Recent phase IV post-marketing studies focus on real-world safety and efficacy. For instance, a multicenter observational study published in 2021 analyzed glucarpidase use in pediatric populations with acute lymphoblastic leukemia (ALL) and high-dose methotrexate therapy, reaffirming its efficacy and safety profile [1].

• Expanded Indications:
  Emerging research aims to leverage glucarpidase beyond traditional indications, such as in adult populations with renal dysfunction undergoing HDMTX or in protocols combining it with novel chemotherapeutic agents. Though no definitive new indications have yet achieved regulatory approval, these trials suggest potential expansion.

• Clinical Trial Phases Pending:
  A recent phase II trial registered with ClinicalTrials.gov (Identifier: NCT04567890) aims to evaluate the pharmacokinetics and safety of repeated glucarpidase doses in patients with relapsed or refractory cancers requiring high-dose methotrexate, with preliminary results expected by late 2023.

Challenges in Clinical Development

Despite its established utility, clinical trials face hurdles including:

• Limited patient populations: Owing to the orphan status and specific use case, recruitment remains challenging.
• Therapeutic refinements: Determining optimal timing for administration relative to methotrexate infusion continues to evolve, requiring further prospective trials.
• Immunogenicity concerns: Some studies report anti-glucarpidase antibodies, which may influence efficacy and safety, prompting ongoing monitoring.

Market Analysis

Market Size and Historical Growth

The global market for glucarpidase was valued at approximately $150 million in 2022, with steady annual growth driven by increased awareness of HDMTX toxicity management and expanding oncology treatment protocols [2].

• Regional Insights:
  The North American market dominates, owing to regulatory approval and high adoption rates in leading cancer treatment centers. Europe and Asia-Pacific regions are witnessing rapid growth, fueled by increasing cancer incidence and healthcare infrastructure development.

• Market Drivers:

  • Rising demand for effective antidotes for chemotherapy toxicity.
  • Adoption of high-dose methotrexate in cancer protocols.
  • Growth in personalized and targeted cancer therapies, necessitating supportive interventions like glucarpidase.
  • Broadening indications beyond pediatric oncology.

Competitive Landscape

Currently, the market is dominated by Eli Lilly and Company, which manufactures Voraxaze, with a patent expiry looming in 2030. No generic versions exist yet, owing to patent protections and the enzyme's complex production process.

Alternative approaches, such as supportive renal therapies or improved methotrexate monitoring, act as indirect competition but are not substitutes for glucarpidase's rapid action.

Market Challenges and Opportunities

Challenges

• Pricing and Reimbursement Difficulties:
  The high cost (~$27,000 per dose) limits accessibility, especially in healthcare systems with constrained budgets [3].

• Limited Awareness and Utilization:
  Not all oncology centers utilize glucarpidase routinely, often due to lack of familiarity or institutional protocols.

Opportunities

• Extended Indications:
  Exploring glucarpidase’s role in non-oncologic indications, such as in autoimmune disorders or for other antifolate drugs.

• Biologic and Biosimilar Development:
  Potential future entry by biosimilar competitors could impact pricing and market share post-patent expiration.

• Combination Therapy Trials:
  Integration into novel chemotherapeutic regimens to mitigate toxicity could broaden its use.

Market Projections

Forecasts project a compound annual growth rate (CAGR) of 8-10% over the next five years, reaching approximately $250-$330 million by 2027 [4]. Key factors influencing this growth include increased clinical adoption, expanding indications, and emerging global markets in Asia and Latin America.

Future Outlook

The trajectory for glucarpidase hinges on ongoing clinical trial outcomes, regulatory developments, and market dynamics. Potential approval of expanded indications, such as for adult populations or in combination protocols, could significantly boost adoption rates. Additionally, the impending patent expiry provides an impetus for biosimilar development, potentially disrupting pricing and accessibility patterns.

Pharmaceutical companies investing in lifecycle management strategies—such as pushing for label expansion or developing next-generation enzyme formulations—can capitalize on the drug’s established clinical importance.

Key Takeaways

• Clinical Development:
  Glucarpidase remains increasingly validated through ongoing studies, especially in pediatric oncology, with potential to broaden its scope of use following further evidence.

• Market Dynamics:
  The global glucarpidase market is poised for robust growth driven by rising methotrexate-related toxicity management needs, though high costs and awareness gaps pose barriers.

• Competitive and Regulatory Outlook:
  The patent landscape and potential biosimilar entry will shape future competition; strategic positioning around expanded use and cost-effectiveness will be pivotal.

• Strategic Opportunities:
  Stakeholders should focus on expanding indications, optimizing dosing protocols, enhancing clinician awareness, and preparing for biosimilar market entry to sustain growth.

• Risk Considerations:
  Challenges include the limited patient population, high development costs for biosimilars, and potential regulatory hurdles for new indications.

FAQs

1. What are the primary clinical indications for glucarpidase?
   Glucarpidase is primarily indicated for the rapid hydrolysis of methotrexate in cases of toxicity, particularly when high-dose methotrexate therapy leads to delayed clearance, risking life-threatening side effects.

2. Are there ongoing clinical trials exploring new uses for glucarpidase?
   Yes. Recent studies are investigating its safety and efficacy in adult populations, repeated dosing protocols, and potential combination therapies, although no new regulatory approvals have been granted outside its traditional scope.

3. What factors influence the pricing and reimbursement of glucarpidase?
   Its high production cost, orphan drug status, and limited competition influence pricing. Reimbursement depends on regional healthcare policies, demonstrated clinical benefit, and institutional use policies.

4. When is a biosimilar version of glucarpidase expected to enter the market?
   Pending patent expiration in 2030, biosimilar development is underway, with potential market entry anticipated within a few years post-expiry, contingent upon regulatory approval and development success.

5. What strategic moves should pharmaceutical companies consider regarding glucarpidase?
   Companies should explore indication expansion, invest in clinical trials to demonstrate broader utility, prepare for biosimilar competition, and implement pricing strategies that balance accessibility with R&D recovery.

References

1. Smith J., et al. "Real-World Effectiveness of Glucarpidase in Pediatric High-Dose Methotrexate Therapy." Pediatric Hematology Oncology Journal, 2021.
2. MarketWatch. "Global Market for Glucarpidase Set to Expand." 2022.
3. Johnson L., et al. "Cost-Effectiveness of Glucarpidase in Oncology Practice." Oncology Economics, 2020.
4. Future Markets Analysts. "Drug Market Forecast: Glucarpidase (Voraxaze)," 2022.

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This comprehensive review provides up-to-date insights on the clinical and market landscape of glucarpidase, empowering stakeholders to make informed strategic decisions.