Adakveo (crizanlizumab-tmca) / Novartis - 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

Increased risk of vaso-occlusive crisis in patients with sickle cell disease treated with crizanlizumab: A real-world analysis using the trinetx database (ASH 2025) - "In this real-world matched cohort analysis, patients with HbSS sickle cell disease treated with crizanlizumab experienced consistently higher rates of VOCs compared to those receiving hydroxyurea. While crizanlizumab was designed to reduce VOC frequency, these findings raise important questions about its effectiveness in clinical practice. These results highlight the continued utility of hydroxyurea and underscore the need for further research to clarify the role of crizanlizumab and to identify which patients are most likely to benefit from its use."

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

Efficacy of crizanlizumab in preventing vaso-oclusive crisis and hospitlalizations in sickle cell disease (ASH 2025) - "This study showed that crizanlizumab alone or with Hydroxyurea was associated with higher rates of VOCs and hospitalization than those not on Crizanlizumab, indicating inferior outcomes and supporting the need for further research into novel therapeutics for SCD."

Clinical • Genetic Disorders • Hematological Disorders • 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

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

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

Efficacy and safety of crizanlizumab in sickle cell disease : A systematic review and meta-analysis (ASH 2025) - "While crizanlizumab targets a key mechanism underlying VOCs in sickle cell disease, current evidence does not demonstrate a statistically significant benefit in reducing VOCs, adverse events, or serious adverse events compared to placebo. The low heterogeneity across studies suggests consistency in findings, but further large-scale clinical trials are warranted to clarify its clinical utility and identify potential subgroups that may benefit."

Retrospective data • Review • 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

IHP-102 compound decreases the adhesion of sickle cell disease RBCs to acutely activated endothelial cells in biochip labs endothelial-on-a-chip assay (ASH 2025) - "IHP-102 inhibits RBC adhesion to acutely activated HUVECs across a diverse dosagespectrum from 100μg/mL down to 1μg/mL. These results further support its potential as an acutetreatment for VOE and are a first demonstration of its activity in human SCD donor blood. Our findingsindicate that IHP-102 exhibits increased effectiveness when the baseline adhesion level is elevated due toheterogeneity in SCD."

Genetic Disorders • Hematological Disorders • Sickle Cell Disease

A phase 2 open-label study of epeleuton in patients with sickle cell disease (ASH 2025) - P2 | "Concomitant treatment with a stable doseof hydroxyurea, crizanlizumab or l-glutamine is permitted during the study. A therapy that can simultaneously impact multiple hallmark features of SCD including RBC morphologyand function as well as cellular adhesion may have an important disease-modifying utility for patientswith SCD. The results of this study are anticipated to confirm the potential of epeleuton to impact rates ofVOC, multiple aspects of SCD pathophysiology, and to guide the design and conduct of a phase 2/3 studyin patients with SCD"

Clinical • P2 data • Beta-Thalassemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Inflammation • Sickle Cell Disease

Description of neurocognition in adult sickle cell disease patients using the NIH toolbox (ASH 2025) - "Similarly, no differences were noted in scores between participants taking Hydroxyurea orCrizanlizumab and those who were not. Adult SCD patients have lower neurocognition scores in all domains using the NIH toolboxcognitive battery of tests when compared to the age-matched normal controls. To our knowledge, we arethe first to report serial neurocognition testing in non-pediatric SCD patients that suggests that diseaseseverity, assessed by degree of anemia and ACS, lowers neurocognition. We believe that this testingapproach can be incorporated into clinical practice."

Clinical • Anemia • Beta-Thalassemia • Cardiovascular • Cognitive Disorders • Genetic Disorders • Hematological Disorders • 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

Maternal and fetal risks in patients with sickle cell disease: Results of the retrospective drepamom study (ASH 2025) - "Beforepregnancy, 39% of patients were receiving baseline treatment, mainly hydroxyurea (HU) in 77% of cases(discontinued in 67% within 3 months after pregnancy diagnosis), and transfusion programs in 23%(alone or combined with HU and/or Crizanlizumab)...Acetylsalicylic acid did not reduce the prevalence of placental abnormalities (p=1) norincrease the risk of postpartum hemorrhage (p=0.637). ConclusionPregnancy in sickle cell disease carries significant maternal and fetal risks and requires management inspecialized centers. Transfusion programs reduce the risk of VOC but must be balanced againstalloimmunization and delayed hemolytic transfusion reactions risks, which is prevalent in this population,highlighting the need to reconsider therapeutic alternatives, including HU, in cases of transfusiondeadlock."

Retrospective data • Genetic Disorders • Gynecology • Hematological Disorders • Infectious Disease • Obstetrics • Postpartum Hemorrhage • Sickle Cell Disease

Thrombotic outcomes in sickle cell disease patients treated with crizanlizumab with or without hydroxyurea: A real-world retrospective cohort analysis using the trinetx database (ASH 2025) - "A total of 1,816 patients met the inclusion criteria, with 908 in each matched cohort. The mean age was29.7 years in the crizanlizumab group and 29.6 years in the control group, with a similar femalepredominance (61.3% vs. 60.8%)."

Real-world • Real-world evidence • Retrospective data • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Etavopivat in adolescents with sickle cell disease: Emerging safety and efficacy findings from the first cohort of the ongoing Phase 1/2 hibiscus kids study (ASH 2025) - P2 | "Stable dose concurrent therapy with hydroxyurea,crizanlizumab and L-glutamine was permitted.Safety endpoints included serious adverse events (SAEs), treatment-emergent adverse events (TEAEs),etavopivat discontinuations, dosing interruptions, and dose reductions. In this preliminary analysis of the HIBISCUS Kids study, the first to investigate a PKR activatorin a pediatric SCD population including children younger than 12 years, etavopivat was relatively welltolerated by adolescents. Cohort 1 enrollment and dosing are complete; weight-based dosing with agranule formulation has begun for cohort 2, children aged 6–<12 years. The study is expected to providefurther insights into the safety, tolerability, and potential clinical benefits of etavopivat in youngerchildren, including those as young as 6 months."

Clinical • P1/2 data • Anemia • Cholestasis • Genetic Disorders • Hematological Disorders • Hepatology • Infectious Disease • Malaria • Sickle Cell Disease

A phase III, multicenter, randomized, placebo controlled, double-blind study to assess efficacy and safety of crizanlizumab (5 mg/kg) versus placebo, with or without hydroxyurea/hydroxycarbamide therapy, in adolescent and adult sickle cell disease patients with frequent vaso-occlusive crises: The sparkle study (ASH 2025) - P3 | "Participantswill log pain episodes via smartphones or a web portal at onset and will remain open until they reportresolution or seek medical assistance, after which data will be transferred to the electronic capturesystem.Patient recruitment is ongoing, with approximately 315 participants expected to enroll. Study completionis anticipated by 2030.In conclusion, the SPARKLE study may offer valuable insights into the clinical effectiveness ofcrizanlizumab in reducing both HCP managed and total VOCs (HCP- and self-managed), offering analternative to current HU/HC therapies."

Clinical • P3 data • Genetic Disorders • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Sickle Cell Disease

Utilization and outcomes of erythropoietin stimulating agents in sickle cell disease patient: A real world data analysis (ASH 2025) - "The population was divided into two cohorts based on receipt of ESAs (EPO, Epoietin alfa,Darbepoetin alfa). Propensity Score matching (PSM) was carried to match age, sex, race, chronic heartfailure, chronic lung disease, neoplasms, chronic kidney disease stages 4 and 5, use of hydroxyurea andcrizanlizumab... This real-world data shows that ESAs use does increase the utilization of hydroxyurea, but itssignificance in improving survival and sickle cell crisis still needs to be evaluated with prognostic studies.The study also highlights potential risks of arterio-venous thrombosis with the use of ESAs."

Clinical • Real-world • Real-world evidence • Anemia • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Coronary Artery Disease • Genetic Disorders • Heart Failure • Hematological Disorders • Ischemic stroke • Myocardial Ischemia • Nephrology • Pulmonary Disease • Renal Disease • Respiratory Diseases • Sickle Cell Disease • Thrombosis

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

Optimizing the right time to start sickle cell therapies. (PubMed, Hematology Am Soc Hematol Educ Program) - "Hydroxyurea, the most widely used DMT, demonstrates strong evidence for early initiation in severe genotypes yet is underutilized due to concerns around long-term effects and adherence challenges. Additional therapies, such as L-glutamine, crizanlizumab, and formerly voxelotor, highlight the growing yet complex therapeutic landscape...Rethinking treatment paradigms to incorporate multiagent approaches, biomarker-driven strategies, and earlier intervention may yield improved outcomes. Ultimately, optimizing the timing of therapy initiation requires moving from reactive to proactive care models that consider risk, clinical severity, and evolving therapeutic options, with the goal of improving quality of life and long-term survival for individuals living with SCD."

Journal • Review • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation