- |||||||||| Journal: Impact of Different Definitions of Vaso-Occlusion on Efficacy Assessments in Sickle Cell Disease Clinical Trials. (Pubmed Central) - Apr 17, 2025
Severe VOCs (exa-cel), VOC (voxelotor), and SCPCs (crizanlizumab and L-glutamine) were more broadly inclusive than severe VOEs (lovo-cel and reni-cel) or painful crisis (hydroxyurea). Clinically, these differences resulted in differing numbers of patients being considered free from vaso-occlusion pain events, underscoring the challenge in comparing frequencies of pain events across SCD clinical trials.
- |||||||||| osivelotor (PF-07940367) / Pfizer
Review, Journal: Osivelotor for the treatment of sickle cell disease. (Pubmed Central) - Apr 3, 2025
However, osivelotor shares the same mechanism of action as voxelotor, and therefore similar limitations regarding its efficacy for which the improvement in Hb level appears misleading. Several issues remain to be resolved before considering any drug approval.
- |||||||||| Oxbryta (voxelotor) / Pfizer
Journal: Plasma inflammatory and angiogenic protein profiling of patients with sickle cell disease. (Pubmed Central) - Mar 7, 2025
While proteins involved in angiogenesis and the IL-18 signalling pathway were further upregulated during VOE, levels of several proteins involved in the IL-18 pathway, T-cell and NK-cell activation and angiogenesis, restored towards levels detected in HCs after curative or disease-modifying treatment. These findings might contribute to a better understanding of SCD pathophysiology and identifying potential new targets for therapeutic interventions.
- |||||||||| Journal: Advantages of the refined Developability Classification System (rDCS) in early discovery. (Pubmed Central) - Feb 19, 2025
The rDCS analysis provided a more differentiated assessment of developability risks associated with oral solid dosage form development, incorporating compound-specific physicochemical attributes and human physiology without the need of preclinical data. The rDCS results were shown to align well with the clinical/marketed formulation strategies for the investigated APIs.
- |||||||||| Oxbryta (voxelotor) / Pfizer
A Case Cohort Study of Individuals with Sickle Cell Disease Referred for Transformative Therapy (HCC Exhibit Hall 3; In-Person) - Jan 15, 2025 - Abstract #TCTASTCTCIBMTR2025TCT_ASTCT_CIBMTR_1535;
Our research highlights the complexity of their baseline complications and the need for evaluation by a SCD specialist prior to referral to the transplant team. Since this initial data collection, several additional individuals have been referred for transformative therapies and will be included in the final analysis.
- |||||||||| Oxbryta (voxelotor) / Pfizer
Journal: Fetal Hemoglobin Decrease During Voxelotor Treatment. (Pubmed Central) - Jan 8, 2025
Our data show a decrease in HbF levels in sickle cell patients after 6?months of treatment with Voxelotor, which is likely to be associated with an increase in the lifespan of red blood cells that are no longer prematurely removed from the circulation, particularly those with low HbF. This work raises the question of the risk of a rebound effect when stopping Voxelotor, which has a short half-life, during the time it takes to increase HbF.
- |||||||||| Oxbryta (voxelotor) / Pfizer
Describing Real-World Use and Voxelotor Adherence Among Youth with Sickle Cell Disease () - Dec 7, 2024 - Abstract #ASH2024ASH_9704;
In contrast to hydroxyurea, however, adherence was not associated with laboratory response. This may be related to differences in the adherence level needed to achieve hematologic response between hydroxyurea and voxelotor.Given our retrospective design, small sample size, shortly study duration, and use of an unvalidated adherence measure, additional studies are warranted to confirm real-world tolerability, best practices on use, and if optimizing voxelotor adherence could have an impact on the outcomes of youth with SCD.
- |||||||||| Oxbryta (voxelotor) / Pfizer, Adakveo (crizanlizumab-tmca) / Novartis
Study of Real-World Treatment Patterns in Patients with Sickle Cell Disease Using US Medicaid Claims Data () - Dec 7, 2024 - Abstract #ASH2024ASH_9703;
Treatment adherence and persistence was suboptimal for all assessed SCD treatments, and approximately 75% of patients discontinued SCD treatment after initiating it on or after Dec 2019. Future studies are needed to evaluate the relationship of SCD treatments with adherence and health outcomes to support the development of strategies to improve adherence and persistence.
- |||||||||| Oxbryta (voxelotor) / Pfizer
Physician Knowledge Regarding Voxelotor for the Treatment of Sickle Cell Disease in England and Wales - a National Survey () - Dec 7, 2024 - Abstract #ASH2024ASH_7413;
In addition, physician attitudes towards access to this medication suggests a centralised model of access to this medication will predominate, which may affect timely access to treatment for those patients living in areas with low rates of SCD. This data will be used to develop efforts at a national level to improve physician knowledge regarding voxelotor and help achieve equitable access to treatment for all SCD patients regardless of geographical location.
- |||||||||| Oxbryta (voxelotor) / Pfizer
Evidence and Gaps in Clinical Outcomes of Voxelotor in Sickle Cell Disease: A Systematic Literature Review () - Dec 7, 2024 - Abstract #ASH2024ASH_7411;
Prior to 2017, hydroxyurea was the only pharmaceutical disease-modifying therapy available for the management of SCD However, recent advances in pharmacotherapy have led to the development of novel disease-modifying therapies that target cellular adhesion, inflammation, oxidant injury, vascular tone, and haemoglobin polymerisation...In 2019, the FDA approved crizanlizumab for adult and paediatric patients aged 16 years and above with SCD and approved voxelotor for adults and paediatric patients ?12 years of age with SCD .The objective of this review r is to summarise the safety and efficacy outcomes of Voxelotor in the treatment of SCD, based on data from clinical trials and real-world settings and to identify any differences or gaps in clinical outcome data from clinical trials and real-world settings through a systematic literature review approach.methodology : We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines...In a retrospective analysis, treatment of 5 patients with SCD with CKD stages I-III resulted in a reduction in urine albumin concentration, in addition to a reduction in Hb levels and absolute reticulocyte counts .Voxelotor is well tolerated with a few minor side effects, as reported in the HOPE and HOPE-KIDS 1 trials, with the most common ones being headache, diarrhoea, and abdominal pain. Most observational studies also reported similar findings.
- |||||||||| Oxbryta (voxelotor) / Pfizer
Disturbed Arterial Flow As a Driver of Perturbed RBC Physiology and Thromboembolic Events in Sickle Cell Disease () - Dec 7, 2024 - Abstract #ASH2024ASH_7365;
The ultimate aim of this work is to underscore the importance of understanding the biomechanical relationship between sRBCs and the unique regimes of flow present in arterial circulation. In doing so, we can then identify regions within the body where turbulence is likely to occur in SCD patients and optimize the implementation of interventions to reduce the burden of thromboembolic events in SCD.
- |||||||||| Oxbryta (voxelotor) / Pfizer, Adakveo (crizanlizumab-tmca) / Novartis
Journal: Novel Pathway and Recent Advances for Targeting Sickle Cell Anemia through Novel Drug Delivery System. (Pubmed Central) - Dec 4, 2024
Furthermore, recent advancements in drug development have led to the discovery of promising candidates targeting specific pathways involved in SCA pathophysiology. Experimental drugs, such as voxelotor and crizanlizumab focus on modifying hemoglobin properties or inhibiting cell adhesion, respectively, thereby preventing sickle cell-related complications and reducing vaso-occlusive crisis frequency.
- |||||||||| Oxbryta (voxelotor) / Pfizer
Enrollment change, Trial completion date, Trial termination, Trial primary completion date: PROSPECT: Oxbryta (clinicaltrials.gov) - Nov 25, 2024
P=N/A, N=262, Terminated,
Experimental drugs, such as voxelotor and crizanlizumab focus on modifying hemoglobin properties or inhibiting cell adhesion, respectively, thereby preventing sickle cell-related complications and reducing vaso-occlusive crisis frequency. N=1000 --> 262 | Trial completion date: Jan 2030 --> Oct 2024 | Recruiting --> Terminated | Trial primary completion date: Jan 2030 --> Oct 2024; Emerging clinical data evaluated by Pfizer and shared with regulatory authorities indicates that the risk profile of voxelotor in people with SCD exceeds the benefits observed in previously generated global research, and requires further assessment.
- |||||||||| Oxbryta (voxelotor) / Pfizer
Trial termination: RESOLVE: Resolution of Sickle Cell Leg Ulcers With Voxelotor (clinicaltrials.gov) - Nov 14, 2024
P3, N=88, Terminated,
In this review, we discuss the mechanisms, trials to date, and future treatment directions of voxelotor. Active, not recruiting --> Terminated; Emerging clinical data evaluated by Pfizer and shared with regulatory authorities indicates that the risk profile of voxelotor in people with SCD exceeds the benefits observed in previously generated global research and requires further assessment.
- |||||||||| Oxbryta (voxelotor) / Pfizer
Enrollment change, Trial completion date, Trial termination, Trial primary completion date: Open-Label Extension of Voxelotor (clinicaltrials.gov) - Nov 14, 2024
P3, N=162, Terminated,
Active, not recruiting --> Terminated; Emerging clinical data evaluated by Pfizer and shared with regulatory authorities indicates that the risk profile of voxelotor in people with SCD exceeds the benefits observed in previously generated global research and requires further assessment. N=300 --> 162 | Trial completion date: Mar 2028 --> Nov 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Mar 2028 --> Oct 2024; Emerging clinical data evaluated by Pfizer and shared with regulatory authorities indicates that the risk profile of voxelotor in people with SCD exceeds the benefits observed in previously generated global research and requires further assessment.
- |||||||||| Oxbryta (voxelotor) / Pfizer
Trial termination: HOPE-KIDS 1: Study to Evaluate the Effect of GBT440 in Pediatrics With Sickle Cell Disease (clinicaltrials.gov) - Nov 13, 2024
P2, N=147, Terminated,
N=300 --> 162 | Trial completion date: Mar 2028 --> Nov 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Mar 2028 --> Oct 2024; Emerging clinical data evaluated by Pfizer and shared with regulatory authorities indicates that the risk profile of voxelotor in people with SCD exceeds the benefits observed in previously generated global research and requires further assessment. Active, not recruiting --> Terminated; Emerging clinical data evaluated by Pfizer and shared with regulatory authorities indicates that the risk profile of voxelotor in people with SCD exceeds the benefits observed in previously generated global research and requires further assessment.
- |||||||||| Oxbryta (voxelotor) / Pfizer
Preclinical, Journal: Metabolic profile characterization of voxelotor in human urine based on in vivo and in vitro models for doping control. (Pubmed Central) - Nov 6, 2024
Analysis of the urine excretion curves revealed that 4 metabolites, along with voxelotor, were suitable for long-term anti-doping monitoring, with a detection window exceeding 20 days. Using both in vivo and in vitro metabolic models, this study provides comprehensive insight into the metabolic profile of voxelotor in human urine for the first time, enhancing the capacity for doping screening and extending the retrospectivity of voxelotor detection.
- |||||||||| Oxbryta (voxelotor) / Pfizer, intravenous immunoglobulin (IVIG) / Guys and St Thomas NHS Foundation Trust
Observational Data on Parvovirus B19 Cases in Patients with Red Cell Disorders in the United Kingdom from 2023-2024 (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_6671;
For the patients with sickle cell disorder, 35 out of the 84 patients were not on any disease modifying therapy, 44 were on hydroxycarbamide, 2 patients were on regular automated exchanges and the remaining patients were on either top up transfusions or a combination of voxelotor and hydroxycarbamide...2 patients were treated for fat embolism syndrome with a red cell exchange and 5 days of plasma exchange, one of these patients was also given intravenous immunoglobulin (IVIG) and the other was given cryoprecipitate and FFP transfusions to treat DIC, both were HbSC...The greater proportion of patients with HbSC (25%) requiring critical care vs HbSS(16.6%) could indicate that patients with HbSC are more vulnerable to developing a more severe disease course. The data collected over 1 year demonstrates that parvovirus B19 infection presents a significant risk to this cohort of patients.
- |||||||||| Oxbryta (voxelotor) / Pfizer, Adakveo (crizanlizumab-tmca) / Novartis
Screening Brain MRI in Sickle Cell Patients: An Insufficiently Implemented Intervention with Critical Importance (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_6656;
Therefore, screening MRI is of paramount importance in all SCD patients, especially in the sicker population. This study is ongoing; with a plan to screen 1000 patients in our center, we intend to implement a strategy of one-time screening MRI for all adult SCD patients with subsequent formal referral for neurocognitive testing.
- |||||||||| Oxbryta (voxelotor) / Pfizer, Adakveo (crizanlizumab-tmca) / Novartis
Buprenorphine Is Associated with Lower Home Opioid Use and Acute Care Utilization in Sickle Cell Disease (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_6643;
While hydroxyurea can reduce vaso-occlusive episodes and lower home opioid use and newer disease modifying agents like crizanlizumab, and l-glutamine reduce pain crises, and voxelotor increases hemoglobin and reduce hemolysis, none effectively modify SCD chronic pain...Another patient with SCD and OUD had 41 acute care visits pre-buprenorphine induction and 19 visits post-buprenorphine, and morphine MME usage decreased by nearly 50% from 392 MME pre-buprenorphine induction to 192 MME post-buprenorphine induction during the treatment period...This study confirms that buprenorphine is acceptable for SCD chronic pain with and without OUD when full-agonist opioid therapy is not satisfactory. The complex and heterogeneous nature of chronic SCD pain necessitates better phenotyping to understand which subphenotypes benefit most from buprenorphine treatment.
- |||||||||| Oxbryta (voxelotor) / Pfizer
Voxelotor Impact after 6 Months on Blood Rheology in Patients with Sickle Cell Disease (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_6629;
P2
A tight regulation of blood viscosity is necessary to maintain proper oxygen delivery and the changes induced by Voxelotor treatment probably require an adaptation to new rheological constrains, which could be favored by gradual Introduction of the treatment. A larger study to evaluate the risk of VOC under Voxelotor treatment and identify predictive biomarkers still needs to be implemented.
- |||||||||| Oxbryta (voxelotor) / Pfizer, Adakveo (crizanlizumab-tmca) / Novartis
Epigenetic Clocks and Accelerated Aging in Sickle Cell Disease (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_6582;
These findings highlight the differential impacts of SCD treatments on epigenetic aging markers. Understanding these relationships can guide personalized therapeutic strategies to mitigate premature aging and improve the quality of life in SCD patients.
- |||||||||| GBT1118 / Pfizer
Concurrent GBT1118 & Losartan Treatment Improves Sickle Cell Nephropathy (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_6566;
Adding GBT1118 to losartan provided additional protection to the kidney, based upon further improvements in urine TBARS, KIM-1, albumin and protein concentrations, while improving the hemoglobin concentration and maintaining stable serum cystatin C and BUN levels. Our results provide support for developing multimodal strategies, such as the combination of voxelotor + losartan, to treat SCA-related CKD in humans.
- |||||||||| Oxbryta (voxelotor) / Pfizer, Adakveo (crizanlizumab-tmca) / Novartis
Cereblon-Based Compounds for Induction of HbF (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_6554;
Furthermore, the ability to significantly induce HBG1/2 expression in HUDEP-2 cells was superior to the one seen for the standard SCD treatment, HU, with levels of HBG1/2 expression 2.6-fold higher (500nM, 72h), at a concentration 200-fold lower. These findings support that ARP-49 shows promising potential for further pre-clinical studies for increasing the production of HbF.
- |||||||||| Oxbryta (voxelotor) / Pfizer
Voxelotor and Red Blood Cell Pyruvate Kinase Activator Enhance Sickle Erythrocyte Deformability By Calcium Efflux (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_6546;
Ca2+ efflux is associated with decreased Band 3 tyrosine phosphorylation for both voxelotor and PKR activator treatments in HbSS RBCs, but not in HbAA RBCs. These findings suggest that Ca2+ efflux is a common pathway through which voxeletor and PKR activators affect Band 3 phosphorylation and RBC deformability; these pathways can be manipulated pharmacologically and understanding this may be relevant to multi-drug therapies.
- |||||||||| Oxbryta (voxelotor) / Pfizer, Adakveo (crizanlizumab-tmca) / Novartis
Low Uptake of FDA-Approved Medications for Sickle Cell Disease Amongst the Adult Medicaid Population in North Carolina (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_6023;
This contrasts with the two-fold higher uptake of opioid analgesics, which treat symptoms of SCD but do not alter comorbidity trajectory. Among the subset of people with SCD who saw a hematologist, uptake rates were markedly higher, and this increase was more pronounced for FDA-approved therapies than for opioids.
- |||||||||| Oxbryta (voxelotor) / Pfizer, Adakveo (crizanlizumab-tmca) / Novartis
Underutilization of Disease-Modifying Therapies in Sickle Cell Disease: A Real-World Analysis from the ASH Research Collaborative Data Hub (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_6018;
DMT use was defined as reported treatment with hydroxyurea, voxelotor, or L-glutamine for ?90 days within a year...Crizanlizumab was not included due to insufficient data for reliable analysis...Additional validations are underway to ensure the accuracy and reliability of our findings. To further understand barriers to broad, preventive DMT use, ongoing analyses will examine the characteristic differences between patients prescribed DMTs stratified by consistency of use, age, and biomarkers of treatment responses, aiming to identify factors associated with successful treatment.
- |||||||||| Oxbryta (voxelotor) / Pfizer, Adakveo (crizanlizumab-tmca) / Novartis
Do Jehovah's Witnesses with Sickle Cell Disease Avoid the Healthcare System? (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_4467;
Although this was a very limited sample size, it suggests that awareness of treatment options is fairly high in the Jehovah's Witness population with SCD. The results continues to reinforce the need to improve general access to care and healthcare delivery for SCD.
- |||||||||| Oxbryta (voxelotor) / Pfizer, Adakveo (crizanlizumab-tmca) / Novartis
Noninvasive, Accessible, Smartphone App for at-Home Hemoglobin Monitoring in Sickle Cell Disease (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_4450;
The correlation between symptoms and Hgb levels calls for future research to better understand the relation of reported symptoms, including vaso-occlusive pain events and Hgb. Overall, the degree of accuracy reported and the correlations between SCD symptoms and Hgb suggest that this noninvasive app is a useful tool for individuals suffering from SCD including users of HU to frequently monitor their Hgb levels, empowering them to better self-manage their condition.
- |||||||||| Oxbryta (voxelotor) / Pfizer
Proposed Use of the Microfluidic Impedance Red Cell Assay (MIRCA) to Identify Individuals with Sickle Cell Disease in Need of Second Line Therapies (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_4251;
Hydroxyurea (HU), a fetal hemoglobin (HbF) inducer, is a mainstay therapy that benefits up to 50% of adult individuals with SCD...Typically, second-line drugs like voxelotor are added to HU after clinical worsening is noted...We plan to use HOI and NOI in combination with traditional clinical laboratory tests to predict the need for additional therapeutic intervention. MIRCA can be used to monitor RBC deformability at routine clinic visits; worsening of deformability and poor laboratory results will trigger initiation of second-line therapies before patients experience clinical decline.
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