Adakveo (crizanlizumab-tmca) / Novartis - LARVOL DELTA

Phase I/II study of the anti-P-selectin antibody crizanlizumab for newly-diagnosed unmethylated glioblastoma (AACR 2026) - "Abstract is embargoed at this time."

P1/2 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Thrombotic Complications in Sickle Cell Anemia (THSNA 2026) - "Management strategies, such as antiplatelet therapy and anticoagulation, may help reduce the risk of thrombosis, and treatment regimens such as hydroxyurea, blood transfusions, and crizanlizumab show promising results. We have reviewed the complex mechanisms that promote thrombotic complications in SCA, discussing their pathophysiology, complications, and advances in targeted therapies to reduce them and improve patient outcomes. No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author."

Anemia • Cardiovascular • Cerebral Hemorrhage • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Hematological Disorders • Inflammation • Nephrology • Renal Disease • Sickle Cell Disease • Venous Thromboembolism • HBB

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

HIGH RATE OF DISCONTINUATION OF CRIZANLIZUMAB TREATMENT IN ADULT PATIENTS WITH SICKLE CELL DISEASE: A SINGLE-CENTER EXPERIENCE (WRMC 2026) - "Our data show that 38% of patients discontinued treatment with crizanlizumab due to intolerance to side effects or lack of efficacy. Considering crizanlizumab is a second-line therapy for patients who are intolerant or unresponsive to hydroxyurea, there is an unmet need to find alternative therapies for sickle cell disease patients who fail both treatments. However, the data also demonstrated that over 30% patients responded to crizanlizumab."

Clinical • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

ADORE: an open platform study of ruxolitinib in combination with other novel therapies in patients with myelofibrosis. (PubMed, Blood Adv) - P1/2 | "Forty-four patients were enrolled in Part 1 of the study of ruxolitinib in combination with siremadlin, rineterkib, sabatolimab, crizanlizumab, or NIS793. Overall, available data from ADORE suggest the feasibility and benefits of combining novel agents with ruxolitinib in patients with suboptimal response to ruxolitinib alone. This trial was registered at www.clinicaltrials.gov as #NCT04097821."

Journal • Hematological Disorders • Myelofibrosis • Neutropenia • Thrombocytopenia • GDF15

PHARMACOKINETICS/PHARMACODYNAMICS, SAFETY AND EFFICACY OF CRIZANLIZUMAB IN PATIENTS WITH SICKLE CELL DISEASE AGED 12 TO <18 YEARS: 2-YEAR DATA FROM THE PHASE 2 SOLACE-KIDS STUDY (EHA 2023) - P2 | "Patients received crizanlizumab on Day 1, Day 15, then every 4 weeks (up to 2 years), with or without hydroxyurea (HU)/Hydroxycarbamide (HC). In this 2-year analysis, crizanlizumab 5 mg/kg with or without concomitant HU/HC has shown a reduction in VOCs resulting in decreased healthcare visits per year, consistent with the established profile of crizanlizumab in adults. Crizanlizumab was safe and well tolerated with no new/unexpected safety concerns. These results confirm 5 mg/kg as an adequate dose in pediatrics with SCD aged 12 to <18 years."

Clinical • P2 data • PK/PD data • Back Pain • CNS Disorders • Genetic Disorders • Hematological Disorders • Infectious Disease • Musculoskeletal Pain • Pain • Pediatrics • Sickle Cell Disease

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

Medication Use Evaluation of Vaso-Occlusive Crises Rates with Crizanlizumab in Patients with Sickle Cell Disease (ASHP 2025) - No abstract available

Clinical • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Medication Use Evaluation of Vaso-Occlusive Crises Rates with Crizanlizumab in Patients with Sickle Cell Disease (ASHP 2025) - "Hosted by the Section of Clinical Specialists and Scientists"

Clinical • Genetic Disorders • Hematological Disorders • 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

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