CLINICAL TRIALS PROFILE FOR OXBRYTA

All Clinical Trials for OXBRYTA

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT05981365 ↗	Voxelotor CYP and Transporter Cocktail Interaction Study	Completed	Pfizer	Phase 1	2023-04-17	This research study is examining multiple doses of voxelotor (a study drug intended for treatment of sickle cell disease) and how it interacts with additional substrates (substrates are drugs or other substances that are metabolized by cytochrome enzymes. The substrates used in this study are FDA approved medications). The study will help to determine the safety and tolerability of the study drugs taken together, as well as the pharmacokinetics (PK) on how your body processes and responds to the combination of the study drug and substrates. Although these drugs are FDA approved, their use in this study is experimental.
NCT05228821 ↗	Voxelotor Cerebral Hemodynamics Study	Not yet recruiting	Global Blood Therapeutics	Phase 4	2022-02-01	This is a Phase 4, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the impact of voxelotor treatment on cerebral blood flow (CBF) in adult and adolescent participants (12-30 years of age) with sickle cell disease (SCD).
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.
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.
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.

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

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Trials by Country for OXBRYTA
Location	Trials
United States	13

Trials by US State

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−

Trials by US State for OXBRYTA
Location	Trials
Texas	2
Georgia	2
Virginia	1
Pennsylvania	1
Ohio	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
Emory University	1

Sponsor Type

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

Pfizer's Oxbryta: A Comprehensive Review of Clinical Trials, Market Impact, and Future Projections

Introduction

Oxbryta, a drug developed to treat sickle cell disease (SCD), has recently been withdrawn from the global market due to significant safety concerns. This decision has far-reaching implications for patients, investors, and the pharmaceutical industry as a whole.

Clinical Trials and Safety Concerns

Pfizer announced the withdrawal of Oxbryta from worldwide markets after new clinical data indicated that the drug's overall benefit no longer outweighs its risks. The data showed an imbalance of deaths and vaso-occlusive crises, which are excruciating episodes of pain characteristic of SCD[1][2][3].

Key Findings

• Clinical trials revealed a higher-than-anticipated number of deaths among patients taking Oxbryta compared to those on placebo.
• The European Medicines Agency (EMA) was already reviewing Oxbryta's safety when these new data emerged, leading to a recommendation to suspend the drug's marketing authorization[4].

Impact on Ongoing Trials

All active clinical trials and expanded access programs for Oxbryta have been discontinued globally. This decision affects not only the patients currently enrolled in these trials but also the broader research community working on SCD treatments[1][2][3].

Market Analysis

Acquisition and Revenue

Pfizer acquired Oxbryta through its $5.4 billion purchase of Global Blood Therapeutics in 2022. At the time, Pfizer projected significant revenue potential from Oxbryta and other SCD treatments developed by Global Blood Therapeutics. However, the actual revenue from Oxbryta was $92 million in the second quarter of 2024, and $328 million globally in 2023, falling short of initial projections[1][2][5].

Market Impact

The withdrawal of Oxbryta is a significant blow to the SCD patient community, which has historically been underserved. Analysts from BMO Capital Markets and Guggenheim Securities noted that this setback increases investor frustrations with Pfizer’s business development track record and raises questions about the company’s ability to grow through the 2025-2030 period[2][5].

Alternative Treatments

Patients currently taking Oxbryta are advised to discuss alternative treatment options with their doctors. Available alternatives include Novartis’ Adakveo and Emmaus Medical’s Endari. Additionally, two gene therapies approved by the FDA in December 2023—bluebird bio’s Lyfgenia and Vertex Pharmaceuticals and CRISPR Therapeutics’ Casgevy—offer potential long-term solutions, although their rollout has been slow and limited to the sickest patients[1][5].

Future Projections and Implications

Financial Projections

Despite the withdrawal, Pfizer does not expect a material impact on its fiscal year 2024 guidance. However, the long-term financial implications could be significant, especially given the billions spent on acquiring Global Blood Therapeutics. Analysts predict that sentiment around Pfizer’s dealmaking prowess could suffer[2][5].

Regulatory Scrutiny

The new safety signals from Oxbryta may lead to increased scrutiny of other SCD treatments, including the newly approved gene therapies. This could affect the risk/cost trade-off analysis for these therapies, particularly since they are generally used in sicker patients[2].

Pfizer’s Pipeline

Pfizer is continuing to work on other SCD treatments, including two experimental medicines originally developed by Global Blood Therapeutics: inclacumab and osivelotor. Osivelotor, the successor to Oxbryta, has shown promise in recent research and is currently in Phase 3 trials[1].

Patient Impact

Treatment Options

The withdrawal of Oxbryta leaves a gap in treatment options for SCD patients. While gene therapies offer a potential lifelong respite, their high cost and complex preparatory process, including chemotherapy, make them less accessible. Patients will need to rely on other available treatments, which may not be as effective or convenient as Oxbryta was intended to be[1][5].

Community Response

The SCD community is scrambling to find alternative treatments, and the sudden loss of Oxbryta has heightened the urgency for new and safer therapies. The community's hope now rests on the successful development and approval of other treatments in Pfizer’s pipeline and from other pharmaceutical companies[5].

Key Takeaways

• Safety Concerns: Oxbryta was withdrawn due to an imbalance of deaths and vaso-occlusive crises in clinical trials.
• Market Impact: The withdrawal affects Pfizer’s revenue projections and investor sentiment, particularly regarding the company’s dealmaking track record.
• Alternative Treatments: Patients are advised to seek alternative treatments such as Adakveo, Endari, and newly approved gene therapies.
• Future Projections: Pfizer continues to develop other SCD treatments, and regulatory scrutiny may increase for new therapies.
• Patient Impact: The withdrawal leaves a significant gap in treatment options for SCD patients, highlighting the need for safe and effective alternatives.

FAQs

Q: Why was Oxbryta withdrawn from the market?

A: Oxbryta was withdrawn due to new clinical data indicating that the drug's overall benefit no longer outweighs its risks, specifically showing an imbalance of deaths and vaso-occlusive crises.

Q: What are the alternative treatments available for SCD patients?

A: Alternative treatments include Novartis’ Adakveo, Emmaus Medical’s Endari, and the newly approved gene therapies Lyfgenia and Casgevy.

Q: How will the withdrawal of Oxbryta affect Pfizer’s financials?

A: The withdrawal is not expected to have a material impact on Pfizer’s fiscal year 2024 guidance, but it may affect long-term financial projections and investor sentiment.

Q: What is the current status of Pfizer’s other SCD treatments in development?

A: Pfizer is continuing to develop two experimental medicines, inclacumab and osivelotor, with osivelotor showing promise in recent research and currently in Phase 3 trials.

Q: How will the withdrawal of Oxbryta impact the SCD patient community?

A: The withdrawal leaves a significant gap in treatment options, increasing the urgency for new and safer therapies. Patients will need to rely on other available treatments until new options become available.

Sources

1. Yahoo Finance: Pfizer to pull sickle cell drug from market, shut down trials.
2. BioSpace: Pfizer Takes Sickle Cell Drug Oxbryta Off Global Market, Cites Risk ...
3. Pharmaceutical Technology: Pfizer to withdraw sickle cell treatment OXBRYTA from market.
4. European Medicines Agency: Oxbryta - referral.
5. BioSpace: Pfizer's Oxbryta Withdrawal Leaves Sickle Cell Community ...