Xromi (hydroxycarbamide) / Nova Labs - LARVOL DELTA

Financial and clinical implications of xromi as a new commercial liquid formulation of hydroxyurea (ASH 2025) - "The sudden integration of a commercial formulation of hydroxyurea has disrupted theability to supply this medication to the pediatric SCD population. While patients covered by Medicaid, atleast in some states, will have uninterrupted access to liquid hydroxyurea, but the ~20-30% of patientscovered by private insurance will now have an overwhelming financial burden for this essentialmedication. This current situation creates real and significant risk of interruption or discontinuation ofhydroxyurea for the vulnerable pediatric SCD population."

Clinical • Genetic Disorders • Hematological Disorders • Rare Diseases • Sickle Cell Disease

PASS of Xromi Comparing Safety and Effectiveness in Children Under 2 Years With Sickle Cell Disease [PRECISE PASS] (clinicaltrials.gov) - P=N/A | N=180 | Recruiting | Sponsor: Nova Laboratories Limited | Trial completion date: Mar 2029 ➔ Jun 2029 | Trial primary completion date: Feb 2029 ➔ Jun 2029

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

PASS of Xromi Comparing Safety and Effectiveness in Children Under 2 Years With Sickle Cell Disease [PRECISE PASS] (clinicaltrials.gov) - P=N/A | N=180 | Recruiting | Sponsor: Nova Laboratories Limited | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Hematological Disorders • Neutropenia • Sickle Cell Disease

PASS of Xromi Comparing Safety and Effectiveness in Children Under 2 Years With Sickle Cell Disease [PRECISE PASS] (clinicaltrials.gov) - P=N/A | N=180 | Not yet recruiting | Sponsor: Nova Laboratories Limited

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

HUPK: Pharmacokinetics of Oral Hydroxyurea Solution (clinicaltrials.gov) - P1/2 | N=33 | Completed | Sponsor: Nova Laboratories Limited | Phase classification: P2 ➔ P1/2

Phase classification • Anemia • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

[VIRTUAL] ELIGIBILITY FOR EMERGING THERAPIES IN SICKLE CELL DISEASE (EHA 2021) - "Background Management of patients with sickle cell disease (SCD) in the UK relies largely on transfusion therapy and hydroxycarbamide alongside supportive care...8 (5.1%) were eligible for Voxelotor only, and 2 (1.3%) were only eligible for Crizanlizumab...This should be kept under review and closer liaison with patients about their VOC may help identify eligible patients. Strict adherence to eligibility based on that of clinical trials is likely to result in very few patients benefitting from these new therapies."

Genetic Disorders • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Oncology • Sickle Cell Disease

[VIRTUAL] STEADFAST: A PHASE II STUDY INVESTIGATING THE EFFECT OF CRIZANLIZUMAB AND STANDARD OF CARE (SOC) VS SOC ALONE ON RENAL FUNCTION IN PATIENTS WITH CHRONIC KIDNEY DISEASE DUE TO SICKLE CELL NEPHROPATHY (EHA 2020) - P2 | "Current standard of care (SoC) for CKD due to SCN includes hydroxyurea/hydroxycarbamide (HU/HC), angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARBs). Conclusion CKD is a common and severe complication of SCD. The Phase II STEADFAST study has been designed to determine the effect of P-selectin inhibition with crizanlizumab on renal function in patients with SCD and CKD due to SCN."

Clinical • P2 data • Acute Kidney Injury • Chronic Kidney Disease • Gene Therapies • Genetic Disorders • Hematological Disorders • Immunology • Ischemic stroke • Nephrology • Renal Disease • Reperfusion Injury • Sickle Cell Disease

[VIRTUAL] Eligibility for emerging therapies in sickle cell disease (BSH 2021) - "Abstract Content: Management of patients with sickle cell disease (SCD) in the UK relies largely on transfusion therapy and hydroxycarbamide alongside supportive care...8 (5.1%) were eligible for voxelotor only, and 2 (1.3%) were only eligible for crizanlizumab...This should be kept under review and closer liaison with patients about their VOC may help identify eligible patients. Strict adherence to eligibility based on that of clinical trials is likely to result in very few patients benefitting from these new therapies."

Genetic Disorders • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Oncology • Sickle Cell Disease

[VIRTUAL] Is There a Clinical Benefit to Switch Hydroxyurea (HU) Drug in Sickle Cell Disease (SCD)? (ASH 2020) - "The main objective was to refine the safety profile of hydroxycarbamide, as well as to identify unexpected toxicities, especially after long-term treatment. In real life setting, a significant improvement of the vasoocclusive symptoms was observed. Improvement of the compliance thanks to a treatment dedicated to the disease is probably one reason for better effectiveness; as suggested bythe lower red blood cell MCV was lower than expected at baseline in patients previously treated with HU. It is also possible that the increase in HbF% observed during the treatment could be another reason for clinical benefit."

Clinical • Genetic Disorders • Hematological Disorders • Myeloproliferative Neoplasm • Neutropenia • Pain • Sickle Cell Disease • Thrombocytopenia

[VIRTUAL] Steadfast: A Randomized, Multicenter, Open-Label, Phase II Study Comparing the Effect of Crizanlizumab Plus Standard of Care (SoC) Versus Soc Alone on Renal Function in Patients with Chronic Kidney Disease Due to Sickle Cell Nephropathy (ASH 2020) - P2 | "The current standard of care (SoC) for CKD due to SCN typically consists of angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARBs), and/or hydroxyurea/hydroxycarbamide (HU/HC). CKD is a severe and common complication of SCD. The Phase II STEADFAST study has been designed to evaluate whether crizanlizumab, in combination with SoC, can reduce albuminuria and slow CKD progression."

Clinical • P2 data • Acute Kidney Injury • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Nephrology • Renal Disease • Reperfusion Injury • Sickle Cell Disease • Transplantation

Pharmacokinetics of Ticagrelor in Infants and Toddlers Aged <24 Months with Sickle Cell Disease (ASH 2019) - P1, P2, P3; "Until recently, the only pharmacological treatment approved for reduction of VOCs was hydroxyurea (hydroxycarbamide), and is recommended for children ≥9 months old with SCD...Of note is that the prasugrel doses used in DOVE only resulted in a mean platelet inhibition of ~20% (Jakubowski et al, 2017)... The present PK results with ticagrelor show a good correlation between predicted and observed exposure, supporting the evaluation of ticagrelor in children with SCD <24 months of age using weight-based dosing. Single-dose ticagrelor, at the doses evaluated, was well tolerated in this population."

PK/PD data

Sickle-Cell Disease Patients’ Attitudes Towards Their Treatment with Hydroxycarbamide (ASH 2019) - "(2011) Pharmacokinetics, pharmacodynamics, and pharmacogenetics of hydroxyurea treatment for children with sickle cell anemia. Blood 118: 4985–4991"

Clinical

Crizanlizumab Versus Placebo, with or without Hydroxyurea/Hydroxycarbamide, in Adolescent and Adult Patients with Sickle Cell Disease and Vaso-Occlusive Crises: A Randomized, Double-Blind, Phase III Study (STAND) (ASH 2019) - P3; "This study is designed to confirm the efficacy and safety of crizanlizumab 5 mg/kg and assess the safety and efficacy of a higher dose (7.5 mg/kg) in patients with SCD and history of VOCs."

Clinical • P3 data • EPO

HUPK: Pharmacokinetics of Oral Hydroxyurea Solution (clinicaltrials.gov) - P2; N=33; Active, not recruiting; Sponsor: Nova Laboratories Limited; Recruiting ➔ Active, not recruiting; N=25 ➔ 33

Clinical • Enrollment change • Enrollment closed • Anemia • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CST3

[VIRTUAL] ESSENTIAL THROMBOCYTHEMIA AND THE RISK OF POLYPHARMACY: ASSESSMENT OF POTENTIAL DRUG-DRUG AND FOOD-DRUG INTERACTIONS (EHA 2021) - "Due to thrombotic risk and associated comorbidities, most patients received antiplatelet drugs (acetylsalicylic acid 13.3%, clopidogrel 13.3%) or systemic anticoagulation alone (acenocoumarol 20.0%, dalteparin 13.3%) or their combination (acetylsalicylic acid + acenocoumarol 6.67%, clopidogrel + rivaroxaban 6.67%)...Hydroxycarbamide led to 2 major DDI with infliximab and 1 moderate DDI with Saccharomyces boulardii. Anagrelide led to 5 major DDI with amiodarone, ciprofloxacin, dalteparin, ivabradine and rivaroxaban, and 2 moderate DDI with carvedilol and omeprazole...To our knowledge, this is the first assessment of polypharmacy and DDI/FDI in ET. However, since there was no correlation of the number of drugs prescribed or of the DDI/FDI with the age of the participants, this might signal that polypharmacy is emerging as a public health issue irrespective of age and points out that the multidisciplinary team involved in the management of ET patients could also include..."

Thrombocytosis

[VIRTUAL] MYELOFIBROSIS TREATMENT WITH RUXOLITINIB IN CLINICAL PRACTICE: AN ANALYSIS OF EFFICACY AND SAFETY OF A SINGLE CENTER (EHA 2021) - "Indications for treatment were constitutional symptoms plus splenomegaly in 10 (62.5%) pts, splenomegaly alone in 5 (31.3%) and intolerance to hydroxycarbamide in 1 (6.25%). Clinicians are usually more alert towards thrombocytopenia but in our series, anemia was the most frequent and serious toxicity having occurred in more than half of the cases. Although, we consider that it is manageable, we would like to propose more strict indications for ruxolitinib dose adjustment according to the hemoglobin cut-off value."

Clinical • Anemia • Hematological Disorders • Myelofibrosis • Polycythemia Vera • Thrombocytopenia • Thrombocytosis • CALR • JAK2

[VIRTUAL] ACUTE CORONARY SYNDROME AND JAK2 V617F MUTATION POSITIVE MYELOPROLIFERATIVE NEOPLASMS: A CARDIOLOGICAL PERSPECTIVE (EHA 2021) - "Recognition by the cardiologists of the peculiar angiography features associated with ACS as initial presentation of PV/ET should prompt hematologic counseling aimed at a tailored treatment strategy. Dual anti-platelet therapy alone may not protect from further thrombotic events and a more comprehensive therapeutic strategy, comprising hydroxycarbamide/phlebotomy, is be advisable in these patients."

Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Hematological Disorders • Myeloproliferative Neoplasm • Myocardial Infarction • Oncology • Polycythemia Vera • Thrombocytosis • Thrombosis • JAK2

JAK 2 positive myeloproliferative neoplasm presenting as stroke, recurrent TIA and isolated third nerve palsy. (PubMed, BMJ Case Rep) - "He was started on hydroxycarbamide and has remained relatively symptom free since then.This case reiterates the known associations between thrombosis and JAK 2 mutation even without overt myeloproliferative neoplasms. It also highlights the need for specialists in stroke to consider screening for JAK 2 mutation in a young patient with cryptogenic stroke with or without polycythemia or thrombocytosis."

Journal • Cardiovascular • Hematological Disorders • Ischemic stroke • Myeloproliferative Neoplasm • Oncology • Thrombocytosis • Thrombosis • JAK2

Stroke and stroke prevention in sickle cell anemia in developed and selected developing countries. (PubMed, J Neurol Sci) - "Children with abnormally high TCD velocities (≥ 200 cm/s) are at high risk of stroke and might benefit from hydroxyurea or hydroxycarbamide (HU) after a period of a successful transition from chronic transfusions. Alternatively, HU is utilized for primary and secondary stroke prevention in developing countries. Further expansion of TCD implementation should be a priority in those settings."

Journal • Review • Anemia • Bone Marrow Transplantation • Cardiovascular • Gene Therapies • Genetic Disorders • Hematological Disorders • Immunology • Ischemic stroke • Sickle Cell Disease • Transplantation

[VIRTUAL] Experience with Pegasys in patients with myeloproliferative neoplasm (BSH 2021) - "Prior studies have shown that inter- feron alfa leads to improvement in JAK2 V617F and CALR driver mutation burdens...15 patients were started on Pegasys as first line treat- ment, 8 patients were previously on venesection, 12 patients on pre- vious cytoreductive therapy (hydroxycarbamide/anagrelide) and 6 other patients were on interferon alpha which were discontinued...Gradual dose titration, careful patient selection and efficient management of side effects can increase efficacy and tolerability of Pegasys. Patients with high risk disease may need combination treatment with JAK2 inhibitors such as Ruxolitinib, this however needs further clinical trials for evaluation"

Clinical • Anemia • Fatigue • Hepatology • Musculoskeletal Pain • Myelofibrosis • Myeloproliferative Neoplasm • Neutropenia • Oncology • Pain • Polycythemia Vera • Thrombocytosis • CALR • TMB

[VIRTUAL] Efficacy and Safety of Pegylated Interferon in Myeloproliferative Neoplasms – A Regional Experience (BSH 2021) - "Abstract Content: Introduction: Hydroxycarbamide (HU) has traditionally been the first-line cytoreductive therapy for high risk patients with Philadelphia negative myeloproliferative neoplasms, but the optimal method of cytoreduction is unclear in younger patients with ET/PV...Of the five patients who were resistant to hydrea or anagrelide, 60% achieved CR after one year on PEG... In this cohort of MPN patients with a young median age but a wide age range, PEG was well tolerated with acceptable times to response and low rates of discontinuation. This is a retrospective study, and thus we have not been able to formally assess the impact of PEG on quality of life. The outcomes of IFN in our patient cohort echoes clinical efficacy seen in other studies."

Clinical • Fatigue • Hematological Disorders • Hepatology • Immunology • Inflammatory Arthritis • Liver Failure • Lupus • Myeloproliferative Neoplasm • Oncology • Venous Thromboembolism

Advances in the Treatment of Polycythemia Vera: Trends in Disease Management. (PubMed, Cureus) - "Phlebotomy and low-dose aspirin suffice in low-risk patients, but cytoreductive therapies are indicated in all high-risk patients (age ≥ 65 years or those with a history of PV-related thrombotic event) and may be considered for low-risk patients with progressively increasing splenomegaly, progressively increasing leucocyte and platelet counts, and for those who do not tolerate phlebotomy. Hydroxyurea/hydroxycarbamide or interferons can be used as first-line drugs...Interferon alfa is especially useful for PV symptoms, and the newer preparation, ropeginterferon alfa-2b, has lesser incidence of flu-like reactions. Ruxolitinib reduces the JAK2V617F mutation burden and is used as a second-line drug. Anagrelide reduces platelet production and can be used in conjunction with hydroxyurea in patients with excessive thrombocytosis. The alkylating agent, busulfan, can also be used as a last resort in patients with a limited life expectancy. Prospective future treatments include..."

Journal • Review • Hematological Disorders • Polycythemia Vera • Thrombocytosis • TMB

[VIRTUAL] The use of hydroxycarbamide in sickle cell patients across the South Thames Sickle and Thalassaemia Network (BSH 2021) - "Other medication options such as L-glutamine, Voxelotor and Crizanlizumab are licensed in USA. It will be made available to teams working across the STSTN as an open-access resource on STSTN website for staff, service users and their families/carers. We hope that this will enable clear informed discussions and facilitate wider uptake of HU."

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

[VIRTUAL] Long-term efficacy of first-line versus second- line pegylated interferon in the treatment of essential thrombocythaemia and polycythaemia vera - results of a single-centre retrospective audit (BSH 2021) - "It is often favoured over hydroxycarbamide, particularly in younger patients with MPN, as its non-cytotoxic nature avoids the long-term concerns sometimes associated with hydroxycarbamide. In conclusion, PegIFN is an effective cytoreductive agent which can induce a complete response in most patients, with good tolera- bility. Although it may take a long time to achieve complete response, this time is not influenced by PegIFN being used as a 1st line or 2nd line therapy."

Retrospective data • CNS Disorders • Dermatology • Fatigue • Hematological Disorders • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • Oncology • Pain • Polycythemia Vera • Pruritus • CALR • JAK2

[VIRTUAL] Dramatic constitutional deterioration following switch to generic imatinib: a case report and one centre’s experience (BSH 2021) - "A 73 year-old woman presented in September 2010 with a myelo- proliferative disorder manifesting as extreme thrombocytosis resistant to hydroxycarbamide therapy and requiring therapeutic apheresis. No gross difference in excipients disclosed at the level of summaries of product characteris- tics (SmPC) offers an obvious explanation for this phenomenon. Arguably by recognising rare cases of severe intolerance to generic TKI formulations, unnecessary switches to more advanced lines of therapy may be avoided and protracted periods of undesirable effects minimized."

Clinical • Anemia • Cardiovascular • Chronic Myeloid Leukemia • Chronic Obstructive Pulmonary Disease • Congestive Heart Failure • Coronary Artery Disease • Fatigue • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hypertension • Immunology • Movement Disorders • Musculoskeletal Pain • Oncology • Pulmonary Disease • Respiratory Diseases • Thrombocytosis