Adakveo (crizanlizumab-tmca) / Novartis - LARVOL DELTA

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

Endothelin Receptor Antagonism in Sickle Cell Disease: Is the Time Now? (PubMed, Can J Physiol Pharmacol) - "Although hydroxyurea remains the most established disease-modifying therapy and that newer approaches such as L-glutamine, voxelotor, crizanlizumab, and gene therapy have expanded the therapeutic landscape, important limitations remain. In parallel, selective ETA antagonists have rapidly advanced owing to multiple FDA approvals for proteinuric kidney diseases outside the context of SCD, in addition to approvals as antihypertensives. Here, we highlight emerging evidence supporting endothelin pathway blockade as a potential targeted therapy for complications such as sickle cell nephropathy, vasculopathy, and pain, while discussing key considerations for future trials."

Journal • Gene Therapies • Genetic Disorders • Hematological Disorders • Nephrology • Pain • Renal Disease • Sickle Cell Disease • EDN1

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

crizanlizumab and inclacumab are equally potent inhibitors of cell adhesion in the blood of patients with sickle cell disease. (PubMed, Blood Red Cells Iron) - "In summary, these results suggest that comparable or higher inhibition of cell adhesion with crizanlizumab vs inclacumab does not correlate with P-selectin binding affinity. Ultimately, clinical trials are required to evaluate how crizanlizumab vs inclacumab translate into treatment outcomes in SCD patients."

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

Benefit-Risk of Voxelotor, Crizanlizumab, and L-Glutamine in Sickle Cell Disease: A Systematic Review. (PubMed, Am J Med Sci) - "The evidence supports therapy-specific benefit signals rather than a pooled class-level conclusion. Benefit-risk interpretation should distinguish vaso-occlusive morbidity from hemoglobin-centered outcomes and account for replication, durability, and safety completeness."

Benefit-risk assessment • Journal • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

A Study to Investigate the Efficacy and Safety of Crizanlizumab (5 mg/kg) Compared With Placebo in Adolescent and Adult Sickle Cell Disease Patients Who Experience Frequent Vaso-Occlusive Crises (SPARKLE) (clinicaltrials.gov) - P3 | N=354 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Apr 2030 ➔ Jul 2030 | Trial primary completion date: Mar 2029 ➔ Jul 2029

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

A Multicenter, Open-Label, Phase 2 Trial Comparing Crizanlizumab Combined With Standard Therapy to Standard Therapy Alone on Renal Function in Patients With Sickle Cell Nephropathy (STEADFAST). (PubMed, Am J Hematol) - No abstract available

Journal • P2 data • Renal Disease

Association between comorbid depression, antidepressant adherence, and disease-modifying therapy adherence among Texas Medicaid patients with sickle cell disease. (PubMed, J Manag Care Spec Pharm) - "Mean PDC 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). Providers should regularly screen for depression and initiate and encourage antidepressant adherence, as this may potentially improve adherence to SCD DMTs. Given the known association between medication adherence and health outcomes, improving adherence to SCD DMTs may improve the health outcomes in this population."

Journal • Reimbursement • Retrospective data • US reimbursement • CNS Disorders • Depression • Genetic Disorders • Hematological Disorders • Mood Disorders • Psychiatry • Sickle Cell Disease

Tumor-Associated Platelets Suppress T-Cell Function and Promote Immune Evasion in TNBC via the P-selectin/ P-selectin glycoprotein ligand-1 Pathway. (PubMed, Cancer Res Commun) - "Using in vitro co-culture systems and in vivo TNBC models, we show that disruption of the P-selectin-PSGL-1 axis, including pharmacologic blockade with the FDA-approved anti-P-selectin antibody Crizanlizumab, restores T cell function and enhances responsiveness to immune checkpoint blockade. Notably, PSGL-1, traditionally recognized for its role in leukocyte trafficking and immune regulation, is co-opted by TAPs to suppress T cell activity, revealing a mechanism of platelet-mediated immune modulation. These findings establish TAPs as active regulators of anti-tumor immunity and identify the P-selectin-PSGL-1 axis as a therapeutically actionable target to overcome resistance to immunotherapy in TNBC."

Journal • Breast Cancer • Immune Modulation • Immunology • Oncology • Solid Tumor • Triple Negative Breast Cancer • SELP

EFFICACY AND SAFETY OF PYRUVATE KINASE-R ACTIVATORS IN SICKLE CELL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS (EHA 2026) - "Three agents approved 2017–2019 briefly widened options, but crizanlizumab lost European approval in August 2023 (STAND trial: no VOC benefit), and voxelotor was withdrawn globally in September 2024 due to a fatal events imbalance the effectively resetting the field...Mitapivat (RISE UP) and etavopivat (HIBISCUS) have both completed Phase 2 RCTs in SCD, but their evidence has never been pooled...Baseline Hb was 8.4–8.8 g/dL across both trials, with 65–81% of participants receiving concomitant hydroxyurea...Abbreviations: CI, confidence interval; DL RE, DerSimonian-Laird random-effects model; Hb, haemoglobin; PP, per-protocol; PKR, pyruvate kinase-R; RR, risk ratio; SAE, serious adverse event; SCD, sickle cell disease; VOC, vaso-occlusive crisis; WMD, weighted mean difference; Wk, week. Panel A (Hb response) pooled estimate is exploratory given cross-trial heterogeneity in response definitions and timepoints; Panel C VOC rate ratio reflects HIBISCUS per-protocol..."

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

PHASE 1/2 HIBISCUS KIDS STUDY OF ETAVOPIVAT IN PEDIATRIC PATIENTS WITH SICKLE CELL DISEASE: SAFETY AND EFFICACY FINDINGS FROM THE COMPLETE FIRST COHORT (EHA 2026) - P2 | "A concomitant stable dose of hydroxyurea, crizanlizumab, or L-glutamine was permitted. Hb at week 24 is the average between week 24 and week 20. ARC, absolute reticulocyte count; BL, baseline; Hb, hemoglobin; LDH, lactate dehydrogenase; SD, standard deviation."

Clinical • P1/2 data • Cholestasis • Gastroenterology • Genetic Disorders • Hematological Disorders • Hepatology • Infectious Disease • Otorhinolaryngology • Pediatrics • Sickle Cell Disease

CURRENT CLINICAL TRIALS FOR NEW THERAPIES IN SICKLE CELL DISEASE DO NOT ADEQUATELY REPRESENT THE PATIENT POPULATION (EHA 2026) - P1, P1/2, P2, P2/3, P3 | "When excluding persons on hydroxyurea, only 8 persons remained eligible. NCT Number Age range (years) Key inclusion criteria (APC/YR) Key exclusion criteria Hb criteria (g/dl) NCT07431398 18–65 ≥4 no HU ≥ 5.5 and ≤ 12 NCT06546670 12-55 2-10 no HU n/a NCT06924970 16-55 2-10 >10 APC/yr ≥5.5 and ≤10.5 NCT05031780 16-55 2-10 >10 APC/yr ≥5.5 and ≤10.5 NCT04624659 12-65 2−15 >15 VOC/yr ≥5.0 and ≤10.0 NCT06612268 >/=12 1-15 >15 VOC and no crizanlizumab ≥5.0 and ≤10.0 NCT06975865 10-65 2-10 SCA only no anticoagulation n/a NCT06439082 >/=12 4-12 No clinical stroke n/a NCT05431088 12-65 2-10 n/a n/a NCT06481306 >/=18 ≥ 4 >8 APC ≥ 5.5 and ≤ 12 Summary/Conclusion Current CT eligibility criteria exclude the majority of real-world adults with SCD...Continued development of safe, effective, and accessible therapies is essential to reduce morbidity, and improve survival and quality of life for individuals living with SCD. Adults With SCD..."

Clinical • Cardiovascular • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Renal Disease • Sickle Cell Disease

EFFICACY AND SAFETY OF ORAL TETRAHYDROURIDINE-DECITABINE (NDEC) IN ADULTS WITH SICKLE CELL DISEASE: RESULTS FROM THE PHASE 2, GLOBAL, RANDOMIZED, PARALLEL-GROUP ASCENT1 TRIAL (EHA 2026) - P2 | "Chronic transfusion therapy, hematopoietic growth factors, recent voxelotor, crizanlizumab, or L-glutamine use were prohibited. Mean changes in total Hb, %HbF, and %F-cells were estimated from a mixed model for repeated measurements with treatment, number of vaso-occlusive crises in the previous year, region and sex nested within visit as fixed factors and baseline level of the parameter as a covariate. BL, baseline; CI, confidence interval; ETD, estimated treatment difference; F-cells, HbF-enriched red blood cells; Hb, hemoglobin; HbF, fetal hemoglobin; HU, hydroxyurea; PBO, placebo; QW, once-weekly; SD, standard deviation; W2CD, weekly on two consecutive days; wk, week."

Clinical • P2 data • Genetic Disorders • Hematological Disorders • Neutropenia • Sickle Cell Disease • Thrombocytosis • DNMT1

Clinical, humanistic, and economic burden of sickle cell disease in The Jazan Region, Saudi Arabia. (PubMed, PLoS One) - "SCD patients face considerable socioeconomic, psychological, and healthcare challenges, with out-of-pocket costs disproportionately burdening lower-income families. Individuals with SCD reported psychological distress, social disruption and reduced quality of life. An apparent variability in professional and familial support was noted, which may have contributed to differences in health care utilization. Additionally, self-reported quality of physician-patient communication and perceived empathy were identified as potential influences for their care-seeking behaviour. These findings reinforce the need for a larger-scale, comprehensive evaluation to confirm them and assess the need for interventions to improve healthcare access and address the psychosocial and economic burdens associated with SCD."

HEOR • Journal • Observational data • CNS Disorders • Genetic Disorders • Hematological Disorders • Pain • 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

Phase I/II study of the anti-P-selectin antibody crizanlizumab for newly-diagnosed unmethylated glioblastoma (AACR 2026) - P2 | " NCT05909618 is a single-center, open-label, 3-arm, non-randomized phase I/II study to evaluate the efficacy, safety, and tolerability of an anti-P-selectin antibody, crizanlizumab, alone (cohort 2) or in combination with nivolumab (cohorts 1 and 3) in patients with GB and melanoma brain metastases. As of the time of submission, approximately 50% of the target accrual has been enrolled across the cohorts. The study remains open, and recruitment is ongoing."

P1/2 data • Brain Cancer • Glioblastoma • Melanoma • Oncology • Solid Tumor • CD8 • MGMT

Characteristics of Young Adults With Sickle Cell Disease Transitioning From Pediatric to Adult Care (ASPHO 2026) - "Regarding clinical and demographic characteristics, there was no statistical difference between those who had two or more adult appointments compared to those who had one or no appointments except for a higher rate of crizanlizumab use (8.6% vs 2%, p < 0.05) and a higher rate of ED visits/year in the past 5 years (1.6 vs 1, p < 0.05) in the transition group... This study demonstrates that many AYA with SCD face significant challenges maintaining continuous care. Understanding specific gaps—such as disease complications and social determinants impacting appointment adherence—can provide critical insight. Data from this single-center underscores the need for comprehensive, multidisciplinary transition programs to improve long-term adult outcomes for individuals with SCD."

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

Crizanlizumab for Treatment of Retinal Vasculopathy With Cerebral Leukoencephalopathy (RVCL) (clinicaltrials.gov) - P2 | N=18 | Completed | Sponsor: Washington University School of Medicine | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Retinal Vasculopathy with Cerebral Leukoencephalopathy

PRIM: Crizanlizumab Pregnancy Outcomes Intensive Monitoring (clinicaltrials.gov) - P=N/A | N=13 | Completed | Sponsor: Novartis Pharmaceuticals

New trial • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

P-selectin as an emerging target for the treatment of primary and secondary brain tumors (AACR 2024) - P2 | "Thus, we have begun an investigator-initiated clinical trial, testing the efficacy of the anti-SELP antibody, Crizanlizumab, alone or in combination with anti-PD-1 antibody, Nivolumab, for GB and melanoma brain metastasis patients (NCT05909618). As such, it has the potential to reduce tumor burden and improve patient outcomes. This work can improve our understanding of GAMs function, which may pave the way for new and effective treatments for primary and secondary brain tumors."

IO biomarker • Brain Cancer • Breast Cancer • CNS Tumor • Glioblastoma • Glioma • Lung Cancer • Melanoma • Oncology • Solid Tumor • SELL • SELP

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

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

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