Oxbryta (voxelotor) / Pfizer - LARVOL DELTA

Advancing Sickle Cell Disease Treatment in Sub-Saharan Africa: Challenges and Opportunities for Disease Modifying Therapies. (PubMed, Am J Hematol) - "Despite established safety and efficacy of hydroxyurea, its use is limited across the region due to inconsistent healthcare infrastructure, high medication and laboratory costs, inadequate clinician training, and persistent disease stigma...Newly approved medications, such as L-glutamine and crizanlizumab, may provide additional benefits to select patients, but are expensive and unavailable. The increased mortality observed in people on voxelotor in Africa highlights the need to ensure the safety of any new medication in varied settings through high-quality research conducted on the continent...SCD management in Africa can be transformed by addressing systemic barriers and leveraging collaborative partnerships, leading to reduced mortality and alleviation of the individual and economic burdens of the disease. It is a moral and economic imperative to prioritize access to SCD treatment in Africa, the region with the greatest disease burden globally."

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

INCIDENT COMPLICATIONS AND TREATMENT USE IN SICKLE CELL DISEASE IN US COMMERCIAL AND MEDICARE-INSURED PATIENTS (ISPOR 2026) - "Incident medication use during follow-up was: antibiotics 19.9%, opioids 19.0%, prescription NSAIDs 18.8%; disease-modifying therapy use was limited (blood transfusion 7.1%, hydroxyurea 5.3%, L-glutamine 0.6%), and uptake of newer therapies (crizanlizumab, voxelotor) was <1%. Incident complications varied by age, with more febrile/infectious events in children and more chronic organ complications in older adults, consistent with a shift in clinical burden across the lifespan. Incident complications varied by age, with more febrile/infectious events in children and more chronic organ complications in older adults, consistent with a shift in clinical burden across the lifespan. No substantial change in complication incidence was observed after availability of newer therapies. Treatment remained predominantly symptomatic with low uptake of disease-modifying newer agents."

Clinical • Medicare • Reimbursement • US reimbursement • Cardiovascular • Genetic Disorders • Hematological Disorders • Infectious Disease • Renal Disease • Sickle Cell Disease

Rethinking Sickle Cell Disease as a Systemic Vasculopathy. (PubMed, Cells) - "While current standard of care treatments, including hydroxyurea and chronic red blood cell transfusions, have been proven to be disease-modifying, newer therapies like crizanlizumab and voxelotor have only proven to manage symptoms. There is still a significant need to understand how we optimize and personalize therapies to improve outcomes for patients. This review highlights the importance of recognizing SCD as a vascular disease to understand its multi-organ complications and heterogeneity of effects."

Journal • Review • Cardiovascular • Gene Therapies • Genetic Disorders • Hematological Disorders • Inflammation • Sickle Cell Disease

Safety and effectiveness of voxelotor in individuals with sickle cell disease in the RETRO and PROSPECT US registries. (PubMed, Blood Adv) - "No new safety findings were identified. Despite inherent limitations of registry studies, voxelotor treatment increased hemoglobin and decreased hemolysis markers in US clinical practice, with no evidence of an increased frequency of APC."

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

Assessing Physical Function in Sickle Cell Patients Taking Voxelotor (clinicaltrials.gov) - P2 | N=6 | Active, not recruiting | Sponsor: Inova Health Care Services | Trial completion date: Dec 2025 ➔ Jun 2026

Trial completion date • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Hemoglobin as a Molecular Glue: Toward Potent Inhibition of HbS Polymerization in Sickle Cell Disease. (PubMed, Adv Healthc Mater) - "Current therapies, such as hydroxyurea and voxelotor, provide only partial symptomatic relief, underscoring the urgent need for transformative strategies. These molecular glues, generated through gene editing or synthetic biology, offer a cell-intrinsic, high-concentration mechanism to counteract HbS polymerization, potentially overcoming the limitations of current therapies. We examine the key challenges in translating this paradigm, including precise structural characterization of polymerization intermediates, efficient intracellular delivery to erythrocytes, temporal regulation under hypoxic conditions, and the mitigation of immunogenicity."

Journal • Review • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Targeted Protein Degradation

Low Use of FDA-Approved Medications for Sickle Cell Disease in Adults. (PubMed, Eur J Haematol) - "Annual prescription rates (≥ 1 claim) of hydroxyurea, L-glutamine, voxelotor, crizanlizumab, and opioid analgesics were calculated over time, and binomial mixed effects models examined associations between prescription and individual characteristics. Males had higher odds of receiving hydroxyurea. Although use of FDA-approved medications for SCD was low, improved access to hematologists may increase medication utilization."

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

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