Oxbryta (voxelotor) / Pfizer - LARVOL DELTA

Impact of Voxelotor on Red Blood Cell Exchange Therapeutic Procedures: Evaluation of Multi-Institutional Procedure Data. (PubMed, J Clin Apher) - "If the HbS total is not used to calculate RBCX replacement volumes in patients taking voxelotor, there is a significantly lower amount of RBC that would be ordered, which would lead to higher HbS after RBCX. Additional studies regarding the role of transfusion in such patients are necessary."

Journal

Prescribing Trends of Disease-Modifying Medications in Texas Medicaid Enrollees with Sickle Cell Disease (ISPOR 2025) - "Hydroxyurea remains the dominant DMT prescribed. The number of monthly users of L-glutamine, voxelotor, and crizanlizumab increased gradually; however, that number remains low."

Medicaid • Reimbursement • US reimbursement • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Characteristics of Patients Enrolled in a Pharmacist Managed Rare Disease Program: Highlighting National Diversity and Representation (ISPOR 2025) - " Among the 7,633 patients enrolled in the Ph-RDP, 55% were diagnosed with sleep disorders, primarily treated with pitolisant, while 34% had sickle cell disease, with voxelotor being the most common medication. The findings highlight the program’s broad reach, including substantial patient enrollment from rural and urban areas and high vulnerability areas as a proxy for providing accessible care to underserved populations. Patient participation and high engagement levels, evidenced by the number of assessments and duration of enrollment, emphasize the program’s potential impact in improving care and health outcomes."

Clinical • CNS Disorders • Genetic Disorders • Hematological Disorders • Rare Diseases • Sickle Cell Disease • Sleep Disorder

Patient Characteristics Associated with the Use of Newly Approved Disease-Modifying Therapy (DMT) for Sickle Cell Disease in Texas Medicaid (ISPOR 2025) - "OBJECTIVES: This study aimed to identify patient characteristics associated with the utilization of new DMTs, including L-glutamine, crizanlizumab-tmca, and voxelotor. Age and greater healthcare utilization (i.e., more outpatient visits, more VOC events, and previous use of hydroxyurea) indicating severe conditions were associated with use of newly approved DMTs."

Clinical • Medicaid • Reimbursement • US reimbursement • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

AWARENESS AND MANAGEMENT OF PRIAPISM IN SICKLE CELL DISEASE - TERTIARY-CENTRE EXPERIENCE AND REGIONAL MODEL OF CARE (EHA 2025) - "64% (16/25) were on disease modifying therapy for SCD: hydroxycarbamide 48% (12/25), red cell transfusion programme 32% (8/25) and voxelotor 4% (1/25). Priapism is a potentially irreversible contributor to infertility in patients with SCD. Fertility preservation is an important part of comprehensive SCD care, particularly in the era of transformative cellular therapies. A history of priapism was documented in males as young as 9 years, emphasising the importance of early and frequent healthcare provider-led discussion of this complication to facilitate early and definitive management."

Beta-Thalassemia • Erectile Dysfunction • Genetic Disorders • Hematological Disorders • Infertility • Pain • Sexual Disorders • Sickle Cell Disease • Urology

IMPROVEMENT IN CEREBRAL OXYGEN SATURATIONS AND VASOREACTIVITY AFTER 12 MONTHS OF VOXELOTOR MEASURED BY NEAR-INFRARED SPECTROSCOPY (NIRS) IN SICKLE CELL DISEASE PATIENTS (EHA 2025) - P2 | "A stable dose for at least 3 months was required for patients treated with hydroxyurea (HU) or angiotensin-converting enzyme inhibitors HU. An improvement in TSI and vasoreactivity was observed in both hemispheres after 1 months of treatment with Voxelotor. This work shows the value of studies such as HEMOPROVE in understanding and making better use of new next-generation compounds such as GBT0 1601 a next-generation HbS polymerization inhibitor for treatment of sickle cell disease."

Clinical • Cardiovascular • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Vascular Neurology

OXIDATIVE METABOLISM IMPROVEMENT DURING EXERCISE IN SICKLE CELL DISEASE PATIENTS TREATED 12 MONTHS WITH VOXELOTOR. ANALYSIS OF HEMOPROVE TRIAL. (EHA 2025) - P2 | ">1 month from a vaso-occlusive crisis (VOC), >3 months from blood transfusion with a stable dose of hydroxyurea). After 12 months of Voxelotor, SCD patients showed improved blood oxygenation and oxidative metabolism during standardized exercise testified by the shift of the exercise blood lactate curve. Hence, despite the increased O2 affinity for Hb under treatment, peripheral oxygen delivery tended to be improved. These data suggest that the [Hb] rise along with hemolysis reduction RBC deformability improvement and peripheral saturation enhancement can counterbalance the higher affinity for O2, favoring O2 delivery, extraction and utilization."

Clinical • Anemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

NEUROPATHIC CHRONIC PAIN IN SICKLE CELL DISEASE IS ASSOCIATED WITH WORSE QUALITY OF LIFE, HEMOLYSIS, AND TNF INFLAMMATION (EHA 2025) - "(Table 1)For TNF cytokines, neuropathic pain was significantly associated with TNFRFS9 (R2 = 0.5, p=0.03) and TWEAK (R2 = 0.4, p=0.03) after adjusting for gender, age, genotype, hydroxyurea, and voxelotor use. SCD individuals living with neuropathic chronic pain experience worse pain quality compared to those with chronic non-neuropathic pain. A distinct laboratory profile emerged for those with the neuropathic chronic pain phenotype with significantly higher hemolysis (elevated LDH and hemolysis index) and inflammation (elevated VCAM and TNF cytokines). This would suggest that, in comparison to other forms of chronic pain, neuropathic pain may be driven by hemolysis and TNF inflammatory pathways."

HEOR • Genetic Disorders • Hematological Disorders • Inflammation • Neuralgia • Pain • Renal Disease • Sickle Cell Disease • TGFA • TNFSF12 • TNFSF14

PEOPLE WITH SICKLE CELL DISEASE EXPERIENCE SUBSTANTIAL SYMPTOM IMPACT DESPITE TREATMENT: FINDINGS FROM THE GLOBAL LISTEN SURVEY (EHA 2025) - "Data for impact of symptoms are reported as the proportion of PwSCD who responded that symptoms have a substantial effect on daily life (responses of "very much" or "a lot") and as a subanalysis by self-reported current SCD treatments: hydroxyurea (HU) only or other treatments (l-glutamine, voxelotor, or crizanlizumab) with or without HU.Overall, 1,145 PwSCD (58% female) with a median age of 30 years completed the LISTEN Survey. Despite the use of HU and other treatments, clinical features of SCD such as fatigue, depressive symptoms, and pain disrupt the lives of PwSCD, and VOCs continue to be experienced regularly. Therefore, more effective treatments are needed to address the unmet needs in managing the impact of SCD."

Clinical • Anemia • CNS Disorders • Fatigue • Genetic Disorders • Hematological Disorders • Mood Disorders • Pain • Psychiatry • Sickle Cell Disease

PRELIMINARY VALIDATION OF THE DYNAMIC SICKLING ASSAY (DSA) AS A DIAGNOSTIC TOOL FOR ASSESSING SICKLE CELL DISEASE SEVERITY AND MONITORING THERAPY EFFICACY (EHA 2025) - "For dose-response treatment of voxelotor, blood was adjusted to 20% hematocrit and treated in vitro at 37°C for 1 hour under continuous agitation with increasing Hb modification doses (0%, 25%, 50%, and 100%)... Parameters derived from DSA kinetic profiles demonstrate superior or comparable performance to existing technologies, positioning the DSA as a precise and comprehensive tool for evaluating the fundamental sickling pathology of SCD and pharmacodynamic efficacy of Hb-modifying therapies. Further development of our standalone DSA device holds significant potential to address the critical need for advanced diagnostics and therapeutic monitoring in both clinical and research settings."

Clinical • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Voxelotor Withdrawal From the Sickle Cell World: A Single Institution Experience (ASPHO 2025) - "We observed more VOE's in individuals that abruptly discontinued Voxelotor as compared to patients who followed a wean schedule. This was supported by evidence of hemolysis on serial labs in the group that abruptly discontinued the medication. This study highlights the importance of the timely guidance received from National Alliance of Sickle Cell Centers (NASCC) for weaning the Voxelotor."

Clinical • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Treatment Course for Prolonged Renal Papillary Necrosis in an Adolescent With Sickle Cell Disease (ASPHO 2025) - "He received 48 hours of ceftriaxone and three days of oral Vitamin K for a mildly prolonged prothrombin time (PT)...Hydroxyurea was increased to 2000mg daily...Over a year later, he continues to be in remission from RPN but has frequent vaso-occlusive pain episodes and transitioned off Voxelotor to chronic exchange transfusions, and is preparing for a sibling-matched hematopoietic stem cell transplant. RPN is rare but can be seen in patients with SCD, without many published cases to determine a specific treatment course. This case demonstrates the utility of supportive care and disease modifying treatments for RPN in SCD."

Bone Marrow Transplantation • Cardiovascular • Genetic Disorders • Hematological Disorders • Nephrology • Pain • Renal Disease • Sickle Cell Disease • Thrombosis

Screen of the ReFRAME Compound Library for Therapeutic Agents to Prevent Red Blood Cell Sickling Using an Improved High Throughput Sickling Assay. (PubMed, ACS Omega) - "We were able to increase the number of blood samples that were adequate for identifying anti-sickling compounds in the improved sickling assay and identified voxelotor and SNS-314 as compounds that successfully prevented sickling. The improved sickling assay will increase access to valuable blood samples from SCD volunteers, providing more opportunities to develop anti-sickling compounds for treating SCD."

Journal • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Use of the Microfluidic Impedance Red Cell Assay (MIRCA) in Sickle Cell Disease. (PubMed, Blood Adv) - "In vitro addition of voxelotor or osivelotor to samples from individuals on CTF improved the deformability of these endogenous RBC. Longitudinally collected NOI and HOI values in HbSS individuals were stable, with a median percent point change of 13.3% and 15.7%, respectively. MIRCA can be used in combination with clinical laboratory tests to monitor RBC deformability as a biomarker of clinical status at routine clinic visits and included in clinical trials of disease modifying agents."

Journal • Cardiovascular • Genetic Disorders • Hematological Disorders • Inflammation • Pain • Pediatrics • Sickle Cell Disease

Evidence and gaps in clinical outcomes of novel pharmacologic therapies for sickle cell disease: A systematic literature review highlighting insights from clinical trials and real-world studies. (PubMed, Blood Rev) - "This systematic review aims to summarise the clinical outcomes of l-glutamine, crizanlizumab, and voxelotor in the treatment of sickle cell disease (SCD) based on clinical trials and real-world data and to identify any gaps in the observations. While some real-world studies have reported a decrease in VOCs and hospitalizations, the results are inconsistent and not conclusive. Further studies are needed to assess the impact of these novel therapies on end-organ-specific complications of SCD."

Clinical data • Journal • Real-world evidence • Review • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

Effect of dalcetrapib, voxelotor and their combination on red blood cell deformability and sickling in sickle cell disease. (PubMed, Clin Hemorheol Microcirc) - "Combining the two molecules caused greater RBC rheological improvement. Our findings suggest that dalcetrapib could block HbS polymerization without affecting HbS oxygen affinity."

Journal • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

The role of nucleation in sickle cell pathophysiology: opportunities for innovative treatments. (PubMed, Ann Med Surg (Lond)) - "For instance, voxelotor, a drug developed using structural insights, binds to HbS and prevents its deoxygenation, reducing nucleation rates. Other strategies, such as CRISPRbased gene editing and allosteric modulators, are emerging as potential therapeutic avenues for altering nucleation kinetics, offering hope for more effective treatments to mitigate the clinical severity of SCA."

Journal • Review • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Osivelotor for the treatment of sickle cell disease. (PubMed, Expert Opin Pharmacother) - "However, osivelotor shares the same mechanism of action as voxelotor, and therefore similar limitations regarding its efficacy for which the improvement in Hb level appears misleading. Several issues remain to be resolved before considering any drug approval."

Journal • Review • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Impact of Different Definitions of Vaso-Occlusion on Efficacy Assessments in Sickle Cell Disease Clinical Trials. (PubMed, Adv Ther) - "Differences exist in definitions of vaso-occlusion and pain events used in SCD clinical trials. Severe VOCs (exa-cel), VOC (voxelotor), and SCPCs (crizanlizumab and L-glutamine) were more broadly inclusive than severe VOEs (lovo-cel and reni-cel) or painful crisis (hydroxyurea). Clinically, these differences resulted in differing numbers of patients being considered free from vaso-occlusion pain events, underscoring the challenge in comparing frequencies of pain events across SCD clinical trials."

Journal • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

A Voxelotor for Sickle Cell Anemia Patients at Highest Risk for Progression of Chronic Kidney Disease (clinicaltrials.gov) - P1/2 | N=12 | Terminated | Sponsor: University of Illinois at Chicago | Trial completion date: Jul 2025 ➔ Oct 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jul 2025 ➔ Oct 2024; Sponsor voluntarily suspended distribution and removed product from the market

Trial completion date • Trial primary completion date • Trial termination • Anemia • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Nephrology • Renal Disease • Sickle Cell Disease

A retrospective research of adverse event reporting system events for voxelotor based on the FAERS database. (PubMed, BMC Pharmacol Toxicol) - "This study systematically analyzed ADRs of voxelotor, highlighting the need for ongoing monitoring and further research on voxelotor's long-term safety and efficacy in treating sickle cell disease."

Adverse events • Journal • Retrospective data • Gastrointestinal Disorder • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

Accelerated Drug Approvals and Patient Trust: Impact of Voxelotor & Crizanlizumab for Sickle Cell Disease. (PubMed, Blood Adv) - "Crizanlizumab and voxelotor were several of the first drugs to receive FDA approval for sickle cell disease (SCD) since the approval of hydroxyurea in 1998. In addition, the impact of these events, without transparent messaging, potentially threatened the fragile trust that providers have more recently been able to build with the SCD population regarding the medical system and research. While there is a need for new therapies in SCD, we must prioritize both safety and efficacy, and maintain trust in this population."

Journal • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

A critique review of fetal hemoglobin modulators through targeting epigenetic regulators for the treatment of sickle cell disease. (PubMed, Life Sci) - "Notably, pharmaceutical approaches like hydroxyurea, l-glutamine, voxelotor, and crizanlizumab, in addition to therapeutic techniques like gene therapies like Casgevy and Lyfgenia, signify noteworthy advancements in the management of issues connected to SCD. It has been demonstrated that inhibiting these targets can prevent the silencing of the gene encoding for the formation of γ-chains and, in turn, increase the synthesis of HbF, providing a possible treatment option for SCD symptoms. These approaches could pave the way for innovative, mechanism-driven therapies that address the unmet medical needs of SCD patients."

Journal • Review • Gene Therapies • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Sickle Cell Disease • HIF1A • ZBTB7A

Reversible Diffusion-Restricting White Matter Lesions Associated with Pain Crisis in Sickle Cell Disease: A Case Report (AAN 2025) - "The patient was treated with hydroxyurea, voxelotor, exchange transfusion, and analgesics. SCD is known to cause several cerebrovascular complications. This case report highlights a rare complication of SCD that presents with severe neurologic dysfunction with cerebral vaso-occlusive crisis involving white matter that is reversible with treatment."

Case report • Clinical • CNS Disorders • Epilepsy • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

Plasma inflammatory and angiogenic protein profiling of patients with sickle cell disease. (PubMed, Br J Haematol) - "From 15 patients, paired samples were collected during both steady-state and vaso-occlusive episodes (VOEs) and from 23 SCD patients longitudinal samples were collected before and after treatment with either voxelotor (n = 10), hydroxyurea (n = 8) or allogeneic haematopoietic stem-cell transplantation (n = 5). While proteins involved in angiogenesis and the IL-18 signalling pathway were further upregulated during VOE, levels of several proteins involved in the IL-18 pathway, T-cell and NK-cell activation and angiogenesis, restored towards levels detected in HCs after curative or disease-modifying treatment. These findings might contribute to a better understanding of SCD pathophysiology and identifying potential new targets for therapeutic interventions."

Journal • Bone Marrow Transplantation • Genetic Disorders • Hematological Disorders • Inflammation • Sickle Cell Disease • Transplantation • ANGPT1 • GZMB • IL10 • IL18 • IL6 • LAG3 • NCR1 • PD-1