Oxbryta (voxelotor) / Pfizer - LARVOL DELTA

Prevalence, treatment patterns, and complications of sickle cell disease in insured US populations: A retrospective study (ASH 2025) - "Use of disease-modifying therapies was limited, with 21.6% and 24.4% of patients using hydroxyurea (HU), 0.5% and 0.8% using L-glutamine, and 12.2% and 15.4% receiving chronic blood transfusions during the baseline and follow-up periods, respectively. Uptake of newer SCD therapies was low, with <1% of patients using crizanlizumab or voxelotor during either period... Treatment of SCD remains dominated by symptom management rather than disease-modifying therapy, as reflected by high utilization of as-needed medications and low uptake of newer therapies. The barriers to accessing disease-modifying therapies and targeted treatments warrant further investigation. Optimization of SCD management is needed to help slow disease progression and reduce complications."

Retrospective data • Asthma • Cardiovascular • Genetic Disorders • Hematological Disorders • Immunology • Infectious Disease • Renal Disease • Respiratory Diseases • Sickle Cell Disease

Impact of acute pain on health care resource utilization and costs in sickle cell disease in the United States (ASH 2025) - "Comparisons were adjusted for demographic characteristics (including age at index, sex, race, ethnicity, geographic region, and type of insurance coverage), baseline clinical characteristics, SCD-related comorbidities (including chronic pulmonary disease, asthma, and hypertension), and SCD treatments (including hydroxyurea, L-glutamine, voxelotor, crizanlizumab-tmca, and erythropoietin-stimulating agents) using multivariable regression models. Acute pain was associated with higher probability of 12-month HCRU and increased associated costs among patients with SCD, highlighting the considerable and previously underrecognized economic burden of acute pain in this population. These findings reinforce the necessity for new treatments to address the substantial unmet need in managing SCD-related acute pain."

HEOR • Asthma • Cardiovascular • Gene Therapies • Genetic Disorders • Hematological Disorders • Hypertension • Immunology • Pain • Pulmonary Disease • Respiratory Diseases • Sickle Cell Disease

Resolving the debate: A systematic review and network meta-analysis of hydroxyurea vs. newer FDA-approved pharmacological therapies in sickle cell disease (ASH 2025) - "However, recent FDA-approved therapies, including Crizanlizumab, Voxelotor, and L-glutamine, offer alternative mechanisms with promising efficacy and safety profiles. This meta-analysis suggests that newer therapies, particularly L-glutamine and Crizanlizumab, offer superior clinical outcomes in terms of reducing vaso-occlusive crises and improving quality of life, with a favorable safety profile. Hydroxyurea remains effective but is ranked lower in efficacy compared to these newer agents. Further studies are needed to refine comparative efficacy and long-term safety data."

Retrospective data • Review • Genetic Disorders • Hematological Disorders • Novel Coronavirus Disease • Sickle Cell Disease

The impact of voxelotor on the reduction in red blood cell transfusions in US patients with sickle cell disease (ASH 2025) - "This study suggests that transfusion rate may be improved with voxelotor and further studies are needed to confirm these findings. The impact of voxelotor on other clinically relevant endpoints, such as VOCs, still needs to be evaluated."

Clinical • Cardiovascular • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • AR

Physician-reported impact of vaso-occlusive crises in people with sickle cell disease: A multinational, real-world survey (ASH 2025) - "Patients who had received a bone marrow transplant, gene therapy, or voxelotor were excluded from the analysis...Of the patients who had been prescribed treatment for at least one year (n=771), 93.9% were treated with a SCD modifying treatment, including hydroxyurea, L-glutamine, and crizanlizumab (1 VOC: 91.9%; 2 VOCs: 93.2%; 3 VOCs: 94.7%; ≥4 VOCs: 97.6%)...Despite receiving modifying treatments and blood transfusions, patients still experienced high clinical morbidity and unemployment burden due to their SCD, with patients suffering the highest numbers of VOCs reporting the greatest impact. Novel SCD modifying treatments which reduce the frequency of VOCs may minimize the burden of disease and improve quality of life for patients."

Clinical • Real-world • Real-world evidence • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Infectious Disease • Sickle Cell Disease

Efficacy of voxelotor in sickle cell disease: A comprehensive meta-analysis of hemoglobin response, hemolysis control, and clinical outcomes across four randomized controlled trials (ASH 2025) - "The safety outcomes were also acceptable, with diarrhea being the most commonly reported adverse effect. These findings illustrate the efficacy of voxelotor in managing hemolysis in SCD and emphasize the need to address broader clinical outcomes for long-term disease control."

Clinical data • Retrospective data • Genetic Disorders • Hematological Disorders • Musculoskeletal Pain • Sickle Cell Disease

Echocardiographic findings over time in sickle cell disease patients: A single-center study (ASH 2025) - "Hydroxyurea was the most common disease-modifying drug taken by 18 patients (78%), followed by Crizanlizumab in 3 patients (14%), then Voxelotor in 2 patients (8%). Changes in findings from patients' initial echocardiograms to their most recent were seen and did vary between those taking disease-modifying drugs and those that were not (most notably the chamber dilation rate), however the sample size was too small to establish any statistically significant trend. We intend to expand this study with a larger cohort and screen 1000 SCD patients at our center, with an ultimate objective of identifying whether a specific disease-modifying drug is associated with any significant changes in echocardiogram findings over time."

Clinical • Cardiomyopathy • Cardiovascular • Genetic Disorders • Hematological Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Sickle Cell Disease

Comparative efficacy of novel therapies for sickle cell disease: A network meta-analysis of hydroxyurea, voxelotor, crizanlizumab, and l-glutamine (ASH 2025) - "In the absence of head-to-head trials, this network meta-analysis offers an indirect comparison of modern SCD therapies. Hydroxyurea and crizanlizumab appear most effective for reducing VOC frequency, while voxelotor provides the greatest improvement in hemoglobin concentration. L-glutamine demonstrates balanced efficacy with a low adverse event rate."

Retrospective data • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Extracellular vesicle dynamics as biomarkers in sickle cell disease across therapies (ASH 2025) - "This study investigates whether EV profiles reflect disease severity and treatment-specific responses, potentially serving as non-invasive biomarkers for inflammation, hemolysis, and therapeutic outcomes in SCD patients treated with hydroxyurea (HU), voxelotor, or transfusion. This capacity enables earlier identification of disease exacerbation, more precise monitoring of therapeutic response, and supports real-time clinical decision-making. Moreover, the feasibility of incorporating EV analysis into point-of-care platforms positions them as promising tools for advancing precision medicine and improving patient outcomes in SCD."

Biomarker • Genetic Disorders • Hematological Disorders • Inflammation • Sickle Cell Disease • CRP

High-throughput oxygen dissociation assay enables rapid screening of hemoglobin oxygen affinity modifying therapies (ASH 2025) - "The distinct and reproducible shifts in ODCs observed with mitapivat, voxelotor, and GBT021601 emphasize RHODA's potential as a powerful tool for evaluating therapeutic efficacy and optimizing dosage strategies for novel Hb-O₂ affinity-modifying drugs. By enabling routine ODC assessment in a microplate format, RHODA stands to accelerate drug development, facilitate genome-editing-based therapies, support blood bank quality control, and inform personalized management of hemoglobinopathies such as SCD."

Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Reassessing voxelotor safety and efficacy: Real-world outcomes from the ASH research collaborative data hub (ASH 2025) - "DMT use wasdefined as EHR-reported treatment with hydroxyurea, voxelotor, or L-glutamine for ≥90 days/year.Transfusions were categorized as DMT if ≥6 occurred/ year. Crizanlizumab was excluded due toinsufficient data...In conclusion, the ASH RC Data Hub is a valuable resource for post-marketingpharmacovigilance studies. Independent analyses can complement industry data, providing additionalvalue through increased transparency and more comprehensive dataset."

Clinical • Real-world • Real-world evidence • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • TINCR

Association between comorbid depression and antidepressant adherence with adherence to disease-modifying therapies in patients with sickle cell disease in Texas Medicaid (ASH 2025) - "Additionally, patients with SCD and comorbiddepression had a significantly higher proportion of patients with a diagnosis of anxiety (76.6% vs. 16.5%)and serious mental health conditions (31.8% vs. 4.0%) during the study period.Among patients with SCD, mean adherence for each SCD DMT was: 38.7±26.7% (hydroxyurea),37.5±29.5% (L-glutamine), 33.9±30.4% (crizanlizumab), and 60.9±34.1% (voxelotor). The prevalence of depression among patients with SCD is high and associated with loweradherence to SCD DMTs. Antidepressant-adherent patients were more likely to adhere to SCD DMTs. SCDproviders should regularly screen for depression, initiate depression treatment when appropriate, andencourage adherence to antidepressants, as this may improve adherence to SCD DMTs and overallhealth outcomes for this population."

Adherence • Clinical • Medicaid • Reimbursement • US reimbursement • CNS Disorders • Depression • Genetic Disorders • Hematological Disorders • Mood Disorders • Psychiatry • Sickle Cell Disease

Rheological effects of voxelotor in SCD: A double-edged sword? (ASH 2025) - P2 | "Patients under hydroxyurea (HU) or angiotensin-convertingenzyme inhibitors (ACEi) had to have received a stable dose for at least three months. However, despite these rheological benefits, the associated increase inhematocrit leads to elevated blood viscosity, particularly at low shear rates. This viscosity rise maycontribute to VOC risk, underscoring the importance of viscosity monitoring in future therapeutic studiestargeting HbS polymerization"

Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Infectious Disease • Septic Shock • Sickle Cell Disease

Impact of voxelotor discontinuation on patients with sickle cell disease (ASH 2025) - "In the 32-patient cohort,the median age of this cohort was 30 years; 21% were male, 69% had HbSS or HbSβ⁰ genotypes, and 44%were on concurrent hydroxyurea therapy. Despite the abrupt market withdrawal of voxelotor, patients were promptly notified.Discontinuation was associated with a noticeable decline in hemoglobin levels, though it did not lead toincreased utilization of healthcare services such as blood transfusions, ED visits, or hospital admissions.These findings emphasize the necessity for careful monitoring of patients after the suddendiscontinuation of disease-modifying therapies and highlight the importance of having accessiblealternative treatments for managing severe anemia in SCD."

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

The weight of stress: Allostatic load as a predictor of vaso-occlusive episodes in adults with sickle cell disease (ASH 2025) - "The association with hospitalization remained nonsignificant.To explore potential confounders, we conducted a multivariate logistic regression analysis including fetalhemoglobin (HbF) levels and therapy status (hydroxyurea, voxelotor, or crizanlizumab). Our preliminary findings suggest that the AL index is a feasible and practical tool forassessing cumulative stress burden in adults with SCD, as it relies on biomarkers routinely collected inclinical care. This pilot study provides early evidence that higher AL is independently associated withincreased VOE frequency and ED utilization. Incorporating AL into clinical assessments may help identifyhigh-risk individuals who could benefit from disease-modifying therapy."

Clinical • Cardiovascular • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • HBB

Hibiscus 2 (Trial-in-Progress): A global, Phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of etavopivat in adolescents and adults with sickle cell disease (ASH 2025) - P3 | "Study population: PwSCD of any genotype and aged ≥12 years are eligible if they have moderate-to-severe anemia, Hb ≥5.0–≤10.0 g/dL at screening, and 2–15 VOC episodes in the year before screening.Concomitant hydroxyurea and/or L-glutamine use is permitted if PwSCD have received stable dosing andare compliant with treatment before screening. Key exclusion criteria are chronic transfusion therapy,use of erythropoiesis-stimulating agents, voxelotor, or crizanlizumab before starting study intervention,and hepatic dysfunction...Study status HIBISCUS 2 is enrolling participants at sites in Australia, Belgium, Brazil, Canada, Colombia, France,Ghana, Greece, India, Italy, Kenya, Lebanon, the Netherlands, Nigeria, Oman, Saudi Arabia, Spain, Turkey,Uganda, the United Kingdom, and the United States. The results from this confirmatory study will provideadditional evidence that etavopivat has the potential to delay or prevent VOCs, enhance Hb levels, andreduce fatigue in PwSCD."

Clinical • P3 data • Anemia • Genetic Disorders • Hematological Disorders • Hepatology • Liver Failure • Sickle Cell Disease

A randomized, double-blind, placebo-controlled trial of a novel BTK inhibitor (rilzabrutinib) in patients with sickle cell disease (SCD) aged 10–65 years: LIBRA Study (ASH 2025) - P3 | "Additionally, participants may beon hydroxyurea and/or L-glutamine (if treated ≥6 months, on a stable dose ≥3 months, with ≥1 VOC whileon stable dose); those not receiving these medications must not plan to initiate them during the study.Key exclusion criteria include a history of stroke or abnormal transcranial doppler, and the use ofcrizanlizumab within 90 days and/or voxelotor within 30 days prior to screening. Other endpoints include change from baseline in QoL, patient globalimpression of fatigue and health status, and biomarkers (biomarkers of inflammation, endothelialactivation, and oxidative stress). This study aims to address a significant unmet need in SCD by evaluatingrilzabrutinib as a novel potential treatment option to reduce VOC burden and improve outcomes in SCD."

Clinical • Anemia • Autoimmune Hemolytic Anemia • Beta-Thalassemia • Cardiovascular • Genetic Disorders • Hematological Disorders • Immune Modulation • Immune Thrombocytopenic Purpura • Immunology • Inflammation • Sickle Cell Disease • Thrombocytopenic Purpura • Thrombosis • HBB

Real-world experience of voxelotor treatment in patients with sickle cell disease (ASH 2025) - "Our data show that most patients were able to obtain voxelotor. Despite about one-third reporting GItoxicity, the majority who filled their prescription reported adherence, suggesting that perceived clinicalbenefit outweighed side effects. Most adult and pediatric patients were able to tolerate maximumdosing."

Clinical • Real-world • Real-world evidence • Anemia • Genetic Disorders • Sickle Cell Disease

Improvement in kidney function after 12 months of voxelotor in sickle cell disease patients (ASH 2025) - P2 | "Patients under hydroxyurea (HU) or angiotensin-convertingenzyme inhibitors (ACEi) had to have received a stable dose for at least three months. During 12 months of treatment with voxelotor, the mGFR decreased in patients withglomerular hyperfiltration and increased in patients with reduced mGFR. The improvement in the mGFRwas correlated with a decrease in plasma HbO₂. ACR and the ability to concentrate urine did not changesignificantly during the follow-up period."

Clinical • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Infectious Disease • Renal Disease • Septic Shock • Sickle Cell Disease

Understanding the menopause transition in sickle cell disease: An analysis of the implementation of the adapted menopause quick 6 (ASH 2025) - "Treatment use included hydroxyurea (45%mean dose: 1117 ± 444 mg/day; median: 1000), chronic exchange transfusion (10%), L-glutamine (2%),and voxelotor (7%). Half reported chronic opioid use (mean: 113 ± 115 MME/day), and 21% were takingmedications against neuropathic pain (e.g., gabapentin)...Midlife women with SCD report a substantial burden of menopausal symptoms—particularly hot flashes,sleep disturbances, and joint pain. Symptom burden appears influenced by age and hematologicparameters, while disease-modifying therapies may mitigate reported symptoms or individuals withsevere disease may not experience the typical hormonal related menopausal symptoms. These findingslay some foundational groundwork for future studies examining the interplay between disease severity,treatment, and reproductive aging in women with SCD."

CNS Disorders • Genetic Disorders • Hematological Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Neuralgia • Orthopedics • Sickle Cell Disease • Sleep Disorder • Women's Health

Targeting hemolysis and raas: Osivelotor and losartan ameliorate sickle cell renal pathology (ASH 2025) - "Osivelotor (GBT021601), a second-generation inhibitor of sickle hemoglobin (Hb)polymerization, shares a mechanism with voxelotor, but has improved pharmacokinetics. The combination treatment led tothe greatest improvement across functional, molecular and structural indicators of kidney damage. Thesefindings suggest that co-targeting hemolytic and RAAS pathways addresses the multifactorial nature ofSCD nephropathy, offering a potentially synergistic therapeutic strategy."

Cardiovascular • Fibrosis • Genetic Disorders • Hematological Disorders • Hypertension • Immunology • Nephrology • Renal Disease • Sickle Cell Disease • CST3 • KIM1

Interim analysis of a placebo controlled study of dronabinol for adults with sickle cell disease and chronic pain (ASH 2025) - "Mass spectrometry for minorcannabinoids was measured to assess for abstinence from other cannabinoids during the study period.30 subjects have been randomized (15 dronabinol/15 placebo), median age 34.3 SD 6.8 years old, 79%were female, 76% HbSS/HbSβ0, 24% HbSC/Hbβ+, 79% on hydroxyurea, 38% on crizanlizumab, and 41%on voxelotor (when it was available). In an interim analysis dronabinol was not associated with SAEs or worsened cognition, the onlyAEs were grade 1 and previously known. Personalized dose titration allowed those who were intolerantto side effects to withdraw early. Dronabinol improved social impact of disease."

Clinical • CNS Disorders • Genetic Disorders • Hematological Disorders • Neuralgia • Pain • Sickle Cell Disease

Is hydroxyurea treatment associated with an increased risk of malignancy in sickle cell disease? a propensity-matched analysis of 27,854 patients in the real world (ASH 2025) - "Propensity scorematching was used to balance cohorts based on demographics, Charlson comorbidities, baselinehemoglobin levels, and other SCD-modifying therapies (e.g., crizanlizumab, voxelotor, L-glutamine). This comprehensive retrospective study found that the use of HU is associated with an increased risk ofboth hematologic and solid cancers in SCD, as well as higher mortality rates and increased healthcareutilization. This association remained significant among non-transfusion-dependent patients, suggestingthat disease severity alone may not fully explain these findings. MDS was the most common type ofhematological malignancy."

Clinical • Real-world • Real-world evidence • Genetic Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Sickle Cell Disease • Skin Cancer • Solid Tumor

30 years of classical hematology drugs in the US: Approvals, costs, and sales (ASH 2025) - "Six drugs have been discontinued (year approved/year discontinued/reason): betrixaban(2017/2020/business), daprodustat (2023/2024/business), fidanacogene elaparvovec(2024/2025/business), oprelvekin (1997/2011/business), peginesatide (2012/2013/safety), and voxelotor(2019/2024/safety).There are limitations to our study. Some drugs have non-classical hematology indications (anticoagulantsin atrial fibrillation; luspatercept in myelodysplastic neoplasm) and/or may also be prescribed by non-classical hematologists (erythropoiesis stimulating agents by nephrologists and medical oncologists)...Classical hematology drugs contribute substantially to US prescription drug spending, with over $70billion in annual sales and medications for thromboembolism accounting for over half of the costs.Approvals have accelerated over the past three decades, doubling each decade. Biologics and biosimilarsnow represent two-thirds of approvals. Continuous-duration treatments, particularly for..."

Anemia • Atrial Fibrillation • Beta-Thalassemia • Cardiovascular • Chemotherapy-Induced Neutropenia • Chronic Kidney Disease • Complement-mediated Rare Disorders • Gene Therapies • Genetic Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Hemophilia • Immune Thrombocytopenic Purpura • Immunology • Myelodysplastic Syndrome • Nephrology • Neutropenia • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • Sickle Cell Disease • Thrombocytopenia • Thrombocytopenic Purpura

Leveraging the ASH Research Collaborative SCD Research Network to Understand Underused Disease Modifying Therapies and Updates from Voxelotor Withdrawal (ASH 2025) - No abstract available

Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease