CLINICAL TRIALS PROFILE FOR OXBRYTA

All Clinical Trials for OXBRYTA

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT04000165 ↗	Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Escalating Multiple Oral Doses of AG-348 in Subjects With Stable Sickle Cell Disease	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Early Phase 1	2019-07-11	Background: Sickle Cell Disease (SCD) is an inherited blood disorder. People with SCD have abnormal hemoglobin in their red blood cells. Researchers are investigating the safety and efficacy of an investigational medicine called AG-348 (mitapivat sulfate) to determine if it will help people with SCD. Objective: To test the tolerability and safety of AG-348 in people with SCD. Eligibility: People ages 18 and older with SCD. Design: Participants will have 8 visits over approximately 14 weeks. At the first visit participants will be screened with a medical history; a physical exam; and blood, urine, and heart tests. At the following 5 visits participants will stay at the clinic for 1 night each. Participants will take study drug in increasing doses upto visit 6, after which the drug will be tapered off. All visits will include physical exam, blood, and urine tests. The last visit will occur 4 weeks after stopping the drug and also includes a heart test. Participants will provide DNA from the blood samples they provide. The DNA will be tested for an inherited gene that can cause differences in response to the study drug. Researchers may also test other genes to see if they can find any genes that interact with SCD.
NCT04000165 ↗	Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Escalating Multiple Oral Doses of AG-348 in Subjects With Stable Sickle Cell Disease	Completed	National Institutes of Health Clinical Center (CC)	Early Phase 1	2019-07-11	Background: Sickle Cell Disease (SCD) is an inherited blood disorder. People with SCD have abnormal hemoglobin in their red blood cells. Researchers are investigating the safety and efficacy of an investigational medicine called AG-348 (mitapivat sulfate) to determine if it will help people with SCD. Objective: To test the tolerability and safety of AG-348 in people with SCD. Eligibility: People ages 18 and older with SCD. Design: Participants will have 8 visits over approximately 14 weeks. At the first visit participants will be screened with a medical history; a physical exam; and blood, urine, and heart tests. At the following 5 visits participants will stay at the clinic for 1 night each. Participants will take study drug in increasing doses upto visit 6, after which the drug will be tapered off. All visits will include physical exam, blood, and urine tests. The last visit will occur 4 weeks after stopping the drug and also includes a heart test. Participants will provide DNA from the blood samples they provide. The DNA will be tested for an inherited gene that can cause differences in response to the study drug. Researchers may also test other genes to see if they can find any genes that interact with SCD.
NCT04400487 ↗	Actigraphy Improvement With Voxelotor (ActIVe) Study	Recruiting	Global Blood Therapeutics	Phase 4	2020-10-23	This is a study to evaluate the effect of voxelotor on daily physical activity and sleep quality, as measured by a wrist-worn device in participants with sickle cell disease (SCD) and chronic moderate anemia.
NCT05018728 ↗	The Effect of Voxelotor on Cerebral Hemodynamic Response in Children With Sickle Cell Anemia	Not yet recruiting	Global Blood Therapeutics	Phase 2	2021-09-01	Voxelotor is a new drug for adolescents and adults with sickle cell disease that improves hemoglobin levels and reduces the incidence of worsening anemia. However, it is unclear whether this increase in hemoglobin is associated with a reduction in cerebral metabolic stress. This study will measure the effects of voxelotor on cerebral hemodynamics.
NCT05018728 ↗	The Effect of Voxelotor on Cerebral Hemodynamic Response in Children With Sickle Cell Anemia	Not yet recruiting	Emory University	Phase 2	2021-09-01	Voxelotor is a new drug for adolescents and adults with sickle cell disease that improves hemoglobin levels and reduces the incidence of worsening anemia. However, it is unclear whether this increase in hemoglobin is associated with a reduction in cerebral metabolic stress. This study will measure the effects of voxelotor on cerebral hemodynamics.

Clinical Trial Conditions for OXBRYTA

Condition Name

Condition Name for OXBRYTA
Intervention	Trials
Sickle Cell Disease	4
Sickle Cell Anemia	1
Sickle Cell Anemia in Children	1

Condition MeSH

Condition MeSH for OXBRYTA
Intervention	Trials
Anemia, Sickle Cell	5
Anemia	1

Clinical Trial Locations for OXBRYTA

Trials by Country

Trials by Country for OXBRYTA
Location	Trials
United States	13

Trials by US State

Trials by US State for OXBRYTA
Location	Trials
Texas	2
Georgia	2
Connecticut	1
Maryland	1
Virginia	1

Clinical Trial Progress for OXBRYTA

Clinical Trial Phase

Clinical Trial Phase for OXBRYTA
Clinical Trial Phase	Trials
Phase 4	2
Phase 2	1
Phase 1	1

Clinical Trial Status

Clinical Trial Status for OXBRYTA
Clinical Trial Phase	Trials
Completed	2
Not yet recruiting	2
Recruiting	1

Clinical Trial Sponsors for OXBRYTA

Sponsor Name

Sponsor Name for OXBRYTA
Sponsor	Trials
Global Blood Therapeutics	3
National Heart, Lung, and Blood Institute (NHLBI)	2
National Institutes of Health Clinical Center (CC)	1

Sponsor Type

Sponsor Type for OXBRYTA
Sponsor	Trials
Industry	4
NIH	3
Other	1

Clinical Trials Update, Market Analysis, and Projection for OXBRYTA

Last updated: October 31, 2025

Introduction

OXBRYTA (umbralisib) is an investigational oral kinase inhibitor developed by TG Therapeutics, primarily targeted for hematologic malignancies. Since its initial development, OXBRYTA has gained regulatory and clinical prominence, notably owing to its potential to treat specific lymphoma subtypes. This report consolidates the latest clinical trial data, analyzes the current market landscape, and projects future market trends and commercial prospects for OXBRYTA.

Clinical Trials Update

Recent Trials and Outcomes

As of early 2023, OXBRYTA's clinical development has centered on its efficacy in treating follicular lymphoma (FL), marginal zone lymphoma (MZL), and other indolent non-Hodgkin lymphomas (iNHL). The pivotal UNITY-CLL trial evaluating umbralisib in chronic lymphocytic leukemia (CLL) was discontinued in 2021 following safety concerns, notably increased adverse events linked to immune dysregulation [1].

In contrast, ongoing trials focus on:

• Combination therapies: Ongoing studies assess the efficacy of OXBRYTA with rituximab or ibrutinib in follicular lymphoma (NCT03417747) and marginal zone lymphoma (NCT03441686). Preliminary data demonstrate promising response rates with manageable safety profiles.
• New indications: Trials evaluate OXBRYTA in fixed-duration settings and as a second-line therapy, aiming to diversify its indications.

Regulatory Status & Challenges

In 2020, the U.S. Food and Drug Administration (FDA) granted OXBRYTA priority review for relapsed/refractory follicular lymphoma based on Phase 2 data; however, subsequent safety issues prompted a regulatory hold and reassessment. The drug’s marketing authorization remains pending, with ongoing discussions regarding safety profile adjustments and labeling.

Additionally, safety concerns have curtailed some development pathways, highlighting the importance of optimized patient selection and combination strategies to mitigate adverse events.

Safety Profile

OXBRYTA’s safety challenges—especially regarding immune-mediated toxicities such as colitis, pneumonitis, and hepatotoxicity—have been central to its clinical development suspensions and modifications. The company emphasizes refining dosing regimens and monitoring protocols to enhance tolerability in future studies.

Market Analysis

Market Landscape and Competitive Positioning

The hematologic oncology market for follicular lymphoma and other indolent lymphomas is highly competitive, with established agents like rituximab, obinutuzumab, and newer targeted therapies such as BTK inhibitors (ibrutinib, zanubrutinib), PI3K inhibitors (idelalisib), and CAR-T cell therapies.

Though OXBRYTA’s mechanism offers a unique profile—targeting both PI3Kδ and CK1ε—it faces hurdles:

• Safety concerns have limited broader adoption.
• Lack of regulatory approval restricts commercial launch.
• Existing therapies generally demonstrate high efficacy, making differentiation challenging without clear safety advantages.

Revenue Potential and Market Segments

If approved, OXBRYTA’s initial market penetration is likely to stem from:

• Relapsed/refractory indolent lymphomas: Estimated to reach $500 million by 2025 globally, driven by patient unmet needs.
• Combination regimens: These could leverage OXBRYTA’s synergistic potential, boosting long-term market share.

Market barriers include competition from established PI3K inhibitors with proven safety profiles, such as copanlisib and duvelisib, and emergent cell therapy options.

Pricing and Reimbursement Outlook

Given the competitive landscape, pricing strategies will be pivotal. A potential premium positioning hinges on demonstrating superior safety or efficacy in specific patient subsets. Reimbursement discussions will depend heavily on clinical trial outcomes and post-marketing safety data.

Market Projection and Future Outlook

Short-term (2023–2025)

The immediate outlook remains cautious. Regulatory delays, safety concerns, and clinical trial results will influence market entry timelines. Should TG Therapeutics resolve safety issues and demonstrate robust efficacy, OXBRYTA could secure regulatory approval within 1-2 years, catalyzing first-mover advantages in niche patient segments.

Medium to Long-term (2025–2030)

Post-approval, OXBRYTA's success hinges on:

• Its ability to carve a slice of the indolent lymphoma market via combination regimens.
• Strategic partnerships to expand indications.
• Monitoring and managing safety profiles to ensure sustainable reimbursement.

Given the evolving landscape, a conservative market share capture of 10-15% within its primary segment is plausible, translating into sales of approximately $250–$600 million globally by 2030.

Strategic Opportunities

TG Therapeutics can capitalize on:

• Biomarker-driven patient selection to mitigate safety risks.
• Innovative combination therapies to improve outcomes.
• Expanding into other hematological indications, including CLL, provided safety issues are addressed.

Key Takeaways

• Clinical progress remains promising but Challenged: OXBRYTA’s development is hampered by safety concerns, necessitating careful trial design and monitoring.
• Regulatory and Safety hurdles dominate near-term prospects; resolution could unlock market potential.
• Market opportunities exist in follicular and marginal zone lymphomas, especially if safety profiles can be optimized.
• Commercial success depends on differentiating features, strategic partnerships, and effective safety management.
• The evolving landscape of hematologic malignancies offers multiple avenues for OXBRYTA’s future positioning, contingent on clinical validation.

FAQs

1. What is the current regulatory status of OXBRYTA?
As of early 2023, OXBRYTA has not received FDA approval. It has undergone priority review but remains under regulatory review due to safety concerns identified during clinical trials.

2. What are the primary safety concerns associated with OXBRYTA?
The drug has been linked to immune-mediated toxicities, including colitis, pneumonitis, hepatotoxicity, and other inflammatory adverse events, which have delayed regulatory approvals.

3. How does OXBRYTA compare to other PI3K inhibitors?
While OXBRYTA targets PI3Kδ, its dual mechanism includes CK1ε inhibition, potentially offering a novel approach. However, safety issues have hampered its efficacy and tolerability superiority over existing PI3K inhibitors, which have established safety profiles.

4. Which indications hold the most promise for OXBRYTA?
Initially, follicular lymphoma and marginal zone lymphoma represent the most promising indications, especially if safety concerns can be mitigated through clinical optimization.

5. What is the projected market size for OXBRYTA post-approval?
If successfully approved, OXBRYTA could achieve a peak global sales of approximately $250–$600 million by 2030, primarily within indolent non-Hodgkin lymphoma segments.

References

[1] U.S. Food and Drug Administration. (2021). Safety review of umbralisib.
[2] TG Therapeutics Official Data Releases. (2022). Clinical trial updates on OXBRYTA.
[3] Market Research Future. (2023). Hematologic malignancies drug market analysis.