CLINICAL TRIALS PROFILE FOR GLEOSTINE

All Clinical Trials for Gleostine

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01989052 ↗	Ph 1/2 CTO With Lomustine for Bevacizumab-Naive Recurrent Glioma	Terminated	Tactical Therapeutics, Inc.	Phase 1	2014-05-01	This is a Phase 1/2 study of the combination of CTO with lomustine in patients with recurrent malignant glioma to be treated at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke. The Primary Objectives are: - Phase 1: To determine the maximum tolerated dose (MTD) of CTO when combined with lomustine among patients with recurrent malignant glioma (World Health Organization (WHO) grade III or IV) who have not been previously treated with bevacizumab. - Phase 2: To assess the efficacy of CTO (either in monotherapy or in combination with lomustine) compared to lomustine alone in patients with recurrent WHO grade IV malignant gliomas that have not been previously treated with bevacizumab based upon 6-month progression free survival (PFS6). Note: This study was terminated early due to funding issues. At the time of termination, the study was still in Phase 1 and no MTD for the combination of CTO and lomustine had been determined for this population. Phase 2 will not proceed.
NCT01989052 ↗	Ph 1/2 CTO With Lomustine for Bevacizumab-Naive Recurrent Glioma	Terminated	Annick Desjardins	Phase 1	2014-05-01	This is a Phase 1/2 study of the combination of CTO with lomustine in patients with recurrent malignant glioma to be treated at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke. The Primary Objectives are: - Phase 1: To determine the maximum tolerated dose (MTD) of CTO when combined with lomustine among patients with recurrent malignant glioma (World Health Organization (WHO) grade III or IV) who have not been previously treated with bevacizumab. - Phase 2: To assess the efficacy of CTO (either in monotherapy or in combination with lomustine) compared to lomustine alone in patients with recurrent WHO grade IV malignant gliomas that have not been previously treated with bevacizumab based upon 6-month progression free survival (PFS6). Note: This study was terminated early due to funding issues. At the time of termination, the study was still in Phase 1 and no MTD for the combination of CTO and lomustine had been determined for this population. Phase 2 will not proceed.
NCT02343406 ↗	Adult Study: ABT-414 Alone or ABT-414 Plus Temozolomide vs. Lomustine or Temozolomide for Recurrent Glioblastoma Pediatric Study: Evaluation of ABT-414 in Children With High Grade Gliomas	Completed	European Organisation for Research and Treatment of Cancer - EORTC	Phase 2	2015-02-17	This study was conducted to evaluate the efficacy and safety of depatuxizumab mafodotin (ABT-414) alone or with temozolomide versus temozolomide or lomustine alone in adult participants with recurrent glioblastoma. The study also included a substudy to evaluate safety, tolerability and pharmacokinetics of ABT-414 in a pediatric population.
NCT02343406 ↗	Adult Study: ABT-414 Alone or ABT-414 Plus Temozolomide vs. Lomustine or Temozolomide for Recurrent Glioblastoma Pediatric Study: Evaluation of ABT-414 in Children With High Grade Gliomas	Completed	AbbVie	Phase 2	2015-02-17	This study was conducted to evaluate the efficacy and safety of depatuxizumab mafodotin (ABT-414) alone or with temozolomide versus temozolomide or lomustine alone in adult participants with recurrent glioblastoma. The study also included a substudy to evaluate safety, tolerability and pharmacokinetics of ABT-414 in a pediatric population.

Clinical Trial Conditions for Gleostine

Condition Name

Condition Name for Gleostine
Intervention	Trials
Glioblastoma	5
Glioblastoma Multiforme	3
Recurrent Anaplastic Astrocytoma	2
Recurrent Glioblastoma	2

Condition MeSH

Condition MeSH for Gleostine
Intervention	Trials
Glioblastoma	9
Glioma	4
Gliosarcoma	2
Neoplasms	2

Clinical Trial Locations for Gleostine

Trials by Country

Trials by Country for Gleostine
Location	Trials
United States	145
Canada	16
Australia	9
Belgium	9
Germany	9

Trials by US State

Trials by US State for Gleostine
Location	Trials
California	7
Washington	6
Texas	6
New York	6
Massachusetts	6

Clinical Trial Progress for Gleostine

Clinical Trial Phase

Clinical Trial Phase for Gleostine
Clinical Trial Phase	Trials
Phase 3	2
Phase 2/Phase 3	1
Phase 2	6

Clinical Trial Status

Clinical Trial Status for Gleostine
Clinical Trial Phase	Trials
Recruiting	5
Not yet recruiting	4
Completed	2

Clinical Trial Sponsors for Gleostine

Sponsor Name

Sponsor Name for Gleostine
Sponsor	Trials
National Cancer Institute (NCI)	3
Worldwide Clinical Trials	1
Darell D. Bigner, MD, PhD	1

Sponsor Type

Sponsor Type for Gleostine
Sponsor	Trials
Other	11
Industry	10
NIH	3

GLEOSTINE: Clinical Trials, Market Analysis, and Projections

Introduction to GLEOSTINE

GLEOSTINE, also known as lomustine, is a chemotherapy drug used in the treatment of various types of cancer, including brain tumors and Hodgkin's lymphoma. Here, we will delve into the current clinical trials, market analysis, and future projections for this drug.

Clinical Trials: NRG-BN011

One of the significant ongoing clinical trials involving GLEOSTINE is the NRG-BN011 study. This Phase III trial is focused on patients with glioblastoma, a type of brain tumor, who have not yet received treatment other than surgery.

Trial Objectives

• The trial aims to determine if the addition of lomustine (GLEOSTINE) to the standard treatment of radiation and temozolomide chemotherapy can extend life or stabilize the cancer in patients with methylated MGMT promoter glioblastoma[4].

Patient Eligibility

• Participants must be over 18 years old and have a glioblastoma that has not been treated with anything other than surgery. The tumor must also have a methylated MGMT promoter, which is a biomarker that helps predict the tumor's response to temozolomide[4].

Treatment Duration

• The treatment involves up to 9 months of chemotherapy with temozolomide and lomustine, in addition to radiation therapy[4].

This trial is crucial as it explores the efficacy of combining GLEOSTINE with standard treatments for glioblastoma, a condition with limited treatment options.

Market Analysis

Current Market Landscape

The market for glioblastoma multiforme (GBM) treatments is dominated by temozolomide and bevacizumab, which accounted for 46% and 51% of the total $549.1 million sales in 2020, respectively. However, the introduction of generic temozolomide and biosimilars of bevacizumab has reduced the market potential for branded drugs[3].

Pricing and Accessibility

GLEOSTINE has faced significant price hikes since its acquisition by NextSource in 2013. The price has increased nearly 1,400% from $50 per capsule to $768 per pill, making it inaccessible to many patients. This price gouging has been criticized by medical professionals, highlighting the need for affordable treatment options[2].

Market Drivers and Barriers

• Drivers: The anticipated approval and launch of new pipeline agents, including cancer vaccines and protein kinase inhibitors, are expected to drive market growth. The GBM market is projected to grow to $868.5 million by 2030 at a Compound Annual Growth Rate (CAGR) of 4.7%[3].
• Barriers: High failure rates in late-stage GBM trials and the genericization of temozolomide are significant barriers to market growth. The lack of generic competitors for drugs like GLEOSTINE, despite patent expiration, also hampers market expansion[3].

Future Projections

Pipeline Agents

Several pipeline agents are expected to enter the GBM market from 2024 onwards, including DCVax-L, regorafenib, and paxalisib, which are projected to generate significant sales. These agents are expected to address unmet needs such as predictive biomarkers for personalized therapy and more efficacious treatments for patients with unmethylated MGMT promoters[3].

Competitive Landscape

The competitive landscape is expected to change with the introduction of new pipeline agents. GLEOSTINE, currently used for recurrent tumors, may see increased usage if the NRG-BN011 trial shows positive results. However, it will need to compete with emerging treatments that offer better efficacy and affordability[3].

Regulatory Environment

The U.S. Food and Drug Administration (FDA) is working to expedite the regulatory review process for drugs like GLEOSTINE that lack generic competitors despite patent expiration. This initiative aims to lower pharmaceutical prices and improve patient access to essential medications[2].

Key Unmet Needs

Predictive Biomarkers

One of the key unmet needs in the GBM market is the development of predictive biomarkers to guide personalized therapy. The MGMT methylation test used in the NRG-BN011 trial is a step in this direction, but more advanced biomarkers are needed to tailor treatments effectively[3].

Efficacious Treatments for Unmethylated MGMT Patients

Patients with unmethylated MGMT promoters typically have a poor response to temozolomide. There is a significant need for more efficacious treatments for this subgroup of patients, which new pipeline agents and combination therapies like the one being tested in NRG-BN011 aim to address[3].

Financial Impact and Accessibility

Pricing Strategies

The significant price hikes of GLEOSTINE have made it financially burdensome for patients. The company's pricing strategy, based on development costs and patient benefits, has been criticized for price gouging. Financial assistance programs are available, but they do not fully mitigate the financial liability for many patients[2].

Regulatory Efforts

Regulatory efforts to expedite the approval of generic competitors and biosimilars are crucial in making treatments more affordable. The FDA's initiatives to lower pharmaceutical prices could significantly impact the accessibility of GLEOSTINE and other essential cancer drugs[2].

Key Takeaways

• Clinical Trials: The NRG-BN011 trial is investigating the efficacy of combining GLEOSTINE with standard treatments for glioblastoma, which could extend life or stabilize the cancer.
• Market Analysis: The GBM market is dominated by temozolomide and bevacizumab, but new pipeline agents are expected to drive growth.
• Pricing and Accessibility: GLEOSTINE's high price due to lack of generic competition is a significant barrier to patient access.
• Future Projections: The market is expected to grow with new pipeline agents, but regulatory efforts are needed to ensure affordability.

FAQs

What is the NRG-BN011 clinical trial about?

The NRG-BN011 trial is a Phase III study that investigates whether adding lomustine (GLEOSTINE) to the standard treatment of radiation and temozolomide chemotherapy can improve outcomes for patients with methylated MGMT promoter glioblastoma[4].

Why has the price of GLEOSTINE increased significantly?

The price of GLEOSTINE has increased nearly 1,400% since 2013 due to price hikes by its new owner, NextSource, despite the drug being off-patent. This has been criticized as price gouging[2].

What are the key unmet needs in the GBM market?

Key unmet needs include the development of predictive biomarkers for personalized therapy and more efficacious treatments for patients with unmethylated MGMT promoters[3].

How is the FDA addressing high pharmaceutical prices?

The FDA is working to expedite the regulatory review process for drugs that lack generic competitors despite patent expiration, aiming to lower pharmaceutical prices and improve patient access[2].

What is the projected market growth for GBM treatments?

The GBM market is projected to grow to $868.5 million by 2030 at a CAGR of 4.7%, driven by the anticipated approval and launch of new pipeline agents[3].

Sources

1. A Phase III Trial of Gleostine® (Lomustine)-Temozolomide Combination Therapy Versus Standard Temozolomide in Patients With Methylated MGMT Promoter Glioblastoma. Baptist MD Anderson Cancer Center.
2. Price of 40-year-old cancer drug hiked 1400% by new owners. CBS News.
3. Glioblastoma Multiforme Forecast and Market Analysis to 2030. GlobalData.
4. NRG-BN011: Second Chemotherapy Drug for Glioblastoma. NRG Oncology.