作者: Qi, Xiuling ; Weyers, Jill J ; Rabadia, Vrajlal ; Strauss, Bradley H ; Connelly, John ; Manca, Dino ; Ghugre, Nilesh R ; Spino, Michael ; Wood, John C ; Wright, Graham A ; Behrouzi, Bita ; Barry, Jennifer

Intramyocardial hemorrhage is an independent predictor of adverse outcomes in ST-segment elevation myocardial infarction (STEMI). Iron deposition resulting from ischemia-reperfusion injury (I/R) is pro-inflammatory and has been associated with adverse remodeling. The role of iron chelation in hemorrhagic acute myocardial infarction (AMI) has never been explored. The purpose of this study was to investigate the cardioprotection offered by the iron-chelating agent deferiprone (DFP) in a porcine AMI model by evaluating hemorrhage neutralization and subsequent cardiac remodeling. Two groups of animals underwent a reperfused AMI procedure: control and DFP treated (N = 7 each). A comprehensive MRI examination was performed in healthy state and up to week 4 post-AMI, followed by histological assessment. Infarct size was not significantly different between the two groups; however, the DFP group demonstrated earlier resolution of hemorrhage (by T2* imaging) and edema (by T2 imaging). Additionally, ventricular enlargement and myocardial hypertrophy (wall thickness and mass) were significantly smaller with DFP, suggesting reduced adverse remodeling, compared to control. The histologic results were consistent with the MRI findings. To date, there is no effective targeted therapy for reperfusion hemorrhage. Our proof-of-concept study is the first to identify hemorrhage-derived iron as a therapeutic target in I/R and exploit the cardioprotective properties of an iron-chelating drug candidate in the setting of AMI. Iron chelation could potentially serve as an adjunctive therapy in hemorrhagic AMI.

2019-11-13·Blood

Neutropenia in Children Treated with Deferiprone or Deferasirox: A Report of the Largest Randomized Trial of Oral Chelators in Transfusion-Dependent Pediatric Patients

作者: Tsang, Yu-Chung ; Felisi, Mariagrazia ; Reggiardo, Giorgio ; Tricta, Fernando ; Kreka, Manika ; Ceci, Adriana ; Tempesta, Bianca ; Spino, Michael ; El-Beshlawy, Amal ; Kattamis, Antonis ; Della Pasqua, Oscar ; Hassab, Hoda ; Sherief, Laila Metwally

Introduction: Agranulocytosis/severe neutropenia is an established adverse event during deferiprone (DFP) use. Less is known about milder episodes, which are frequently transient despite continuous deferiprone use. To provide further insight into this topic, we compared the incidence of neutropenia during DFP or deferasirox (DFX) treatment in the randomized Deferiprone Evaluation in Paediatrics (DEEP-2) trial, where blood neutrophil count was regularly monitored in patients randomized to be treated with DFP or DFX.Methods: DEEP-2 was a multicenter, randomized, 12-month, open-label trial comparing DFP vs DFX in pediatric (<18 years old) patients with transfusion-dependent hemoglobinopathies. 390 patients from 22 centers in 7 countries were randomized (1:1 DFP:DFX) and received at least one dose of the study medication (193 on DFP and 197 on DFX). Neutrophil count was regularly assessed every 7 +/-7 days in all patients. Neutrophil counts <500/mm3 were classified as agranulocytosis/severe neutropenia, 500 - <1,000 /mm3 as moderate neutropenia, and 1,000 - <1,500 /mm3 as mild neutropenia. The incidence of neutrophil counts below the threshold of neutropenia (1,500/mm3) and the rate of reported episodes of neutropenia as identified by the treating physician were compared between the two treatments. An ANOVA model was used to compare the time to neutropenia and time for its resolution between the two treatment groups. To compare the cumulative hazard curves was used the Kaplan-Meier log rank test.Results: 3579 and 4027 neutrophil counts were available for DFP- and DFX-treated patients, respectively. 47 (1.3%) of the total counts in 24 (12.4%) of the 193 DFP-treated patients versus 48 (1.2%) of the total counts in 27 (13.7%) of the 197 DFX-treated patients were below 1,500/mm3. Of these, 28 cases in 23 DFP-treated patients and 15 cases in 11 DFX-treated patients were reported by the treating physician as neutropenia, corresponding to a global incidence rate 11.9% for DFP and 5.6% for DFX (p=0.081, Chi-Square test). 23 (82.1%) of the 28 episodes of neutropenia during DFP use were considered drug related vs 2 (13.3%) of the 15 episodes during DFX use (p-value < 0.001, Fisher Exact test) (table 1).The mean (SD) treatment duration with either DFP or DFX prior to diagnosis of mild or moderated neutropenia was 127 (96.1) days and 101 (85.7) respectively. All those episodes, except for 2, resolved within a mean time of 13 days (1 - 42 days) in DFP-treated patients and 18 days (6 - 46 days) in DFX-treated patients. The 2 cases where neutropenia did not resolve were diagnosed as constitutional neutropenia and bone marrow suppression. There was no significant difference in those results between the two treatment groups as assessed by one-way ANOVA(p = 0.379), Log-Rank test (p = 0.065) or cumulative-hazard and Kaplan-Meier.During the study 3 events of agranulocytosis occurred, all in patients treated with DFP and not included in the present analysis. All 3 episodes resolved.Conclusion: Data from the largest randomized trial of oral chelators in transfusion-dependent pediatric patients provide evidence that, a drop in the neutrophil count below the threshold for mild neutropenia is very common (>10% of patients) for both DFP and DFX treated patients. All episodes of neutropenia, except for 2 with specific etiology, resolved, irrespective of their severity and of chelator used. A causal relationship of neutropenia to chelator use varied based on the chelator; the majority of events observed during DFP use were assessed by the clinician as drug related, whereas the majority of events observed during DFX use were assessed unrelated to its use. These data indicate that while agranulocytosis rate in DFP patients is not changed from previous reports, moderate/mild neutropenia represent discrete events in patients undergoing oral iron chelation therapy.DisclosuresTricta: ApoPharma: Employment. Della Pasqua:GlaxoSmithKline: Employment. Kattamis:Ionis: Membership on an entity's Board of Directors or advisory committees; ViFOR: Membership on an entity's Board of Directors or advisory committees; Vertex: Membership on an entity's Board of Directors or advisory committees; Apopharma: Honoraria; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Reggiardo:CVBF: Consultancy. Spino:ApoPharma: Employment. Tsang:Apotex Inc.: Employment.

2019-11-13·Blood

Randomized Controlled Trial of the Efficacy and Safety of Deferiprone in Iron-Overloaded Patients with Sickle Cell Disease or Other Anemias

作者: Tsang, Yu-Chung ; Hamdy, Mona ; Stilman, Anne ; Shaw, Dian ; Kwiatkowski, Janet L. ; Abdulrahman, Alshehri ; Lee, David ; Badr, Mohamed Ahmed ; Bejaoui, Mohamed ; Toiber Temin, Noemi ; Williams, Suzan ; Sinclair, Jodie ; Ebeid, Fatma Soliman Elsayed ; Tricta, Fernando ; Inusa, Baba PD ; El-Beshlawy, Amal ; Verissimo, Monica PINHEIRO DE ALMEIDA ; Spino, Michael ; Fradette, Caroline ; Kanter, Julie ; Chan, Theresa ; Rozova, Anna ; Elalfy, Mohsen Saleh ; Kilinc, Yurdanur

Background: Patients with sickle cell disease (SCD) or other rare anemias whose care includes chronic blood transfusions must receive iron chelation to prevent the morbidity of iron overload. Currently, only deferoxamine (DFO) and deferasirox (DFX) are approved chelators in these patient populations. This randomized open-label trial evaluated if the efficacy of deferiprone (DFP) was non-inferior to DFO. DFO was used as the comparator product since DFX was not approved as first-line treatment for SCD at trial initiation.Methods: Participants at 27 sites in 8 countries were randomized in a 2:1 ratio to receive either DFP or DFO for up to 12 months. Those with lower transfusional iron input and/or less severe iron load were prescribed either DFP 25 mg/kg of body weight t.i.d. or DFO 20 mg/kg (children) or 40 mg/kg (adults); those with higher iron input and/or more severe iron load received either DFP 33 mg/kg t.i.d. or DFO up to 40 mg/kg (children) or 50 mg/kg (adults). Dosages could be adjusted over the course of the trial if necessary. Efficacy endpoints were the changes from baseline in liver iron concentration (LIC), cardiac iron, and serum ferritin (SF) at Month 12. The primary endpoint was based on LIC, and for the demonstration of non-inferiority of DFP to DFO, the upper limit of the 95% confidence interval for the difference between treatments had to be no more than 2 mg/g dry weight (dw). All patients had their neutrophil count monitored weekly, whereas other safety assessments and compliance with study therapy were evaluated monthly. Acceptable compliance was defined as taking 80% to 120% of the prescribed dosage.Results: A total of 228 of the targeted 300 patients were dosed with 152 receiving DFP and 76 receiving DFO, to assess non-inferiority. There were no significant differences between the groups in any demographic measures: in each treatment group, 84% of patients had SCD and the remainder had other, rarer forms of transfusion-dependent anemia. Mean age at enrollment was 16.9 years (± 9.6); 53.1% of patients were male; and 77.2% were white, 16.2% black, and 6.6% multi-racial. Over the course of the study, 69% of patients in the DFP group and 79% in the DFO group had acceptable compliance with treatment.Based on the Pocock's α spending function, a more stringent confidence level of 96.01% was applied to the calculation of confidence interval for the evaluation of non-inferiority. For the primary efficacy endpoint, the least squares (LS) mean change in LIC (measured as mg/g dw) was -4.04 for DFP, -4.45 for DFO; the upper limit of the 96.01% confidence interval for the difference was 1.57, thereby demonstrating non-inferiority of DFP to DFO. The upper limit for the subpopulation of patients with SCD also met the non-inferiority criterion. For the secondary endpoints, the change in cardiac iron (measured as ms on MRI T2*, log-transformed) was approximately -0.02 for both; and for SF (measured as μg/L), it was -415 vs. -750 for DFP vs. DFO, respectively. The difference between the groups was not statistically significant for both endpoints.With respect to safety, there was no statistically significant difference between the groups in the overall rate of adverse events (AEs), treatment-related AEs, serious AEs, or withdrawals from the study due to AEs. Agranulocytosis was seen in 1 DFP patient vs. no DFO patients, while events of less severe episodes of neutropenia occurred in 4 vs. 1, respectively. All episodes of agranulocytosis and neutropenia resolved. There was no significant treatment group difference in the rates of any of the serious AEs.Conclusion: The efficacy of DFP for the treatment of iron overload in patients with SCD or other rare anemias is not inferior to that of DFO, as assessed by changes in liver iron concentration. non-inferiority was supported by the endpoints on cardiac iron load and SF. The safety profile of DFP was acceptable and was similar to that previously seen in thalassemia patients, and its use was not associated with unexpected serious adverse events. The results of this study support the use of DFP for the treatment of iron overload in patients with SCD or other rare transfusion-dependent anemias.Note: The authors listed here are presenting these findings on behalf of all investigators who participated in the study.DisclosuresKwiatkowski: Terumo: Research Funding; Imara: Consultancy; bluebird bio, Inc.: Consultancy, Research Funding; Agios: Consultancy; Novartis: Research Funding; Celgene: Consultancy; Apopharma: Research Funding. Fradette:ApoPharma: Employment. Kanter:Sangamo: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Imara: Consultancy; Guidepoint Global: Consultancy; GLG: Consultancy; Cowen: Consultancy; Jeffries: Consultancy; Medscape: Honoraria; Rockpointe: Honoraria; Peerview: Honoraria; SCDAA: Membership on an entity's Board of Directors or advisory committees; NHLBI: Membership on an entity's Board of Directors or advisory committees; bluebird bio, Inc.: Consultancy; Modus: Consultancy, Honoraria. Tsang:Apotex Inc.: Employment. Stilman:ApoPharma: Employment. Rozova:ApoPharma: Employment. Sinclair:ApoPharma: Employment. Shaw:ApoPharma: Employment. Chan:ApoPharma: Employment. Toiber Temin:ApoPharma: Employment. Lee:ApoPharma: Employment. Spino:ApoPharma: Employment. Tricta:ApoPharma: Employment.OffLabel Disclosure:Deferiprone is an oral iron chelator.

项与 ApoPharma, Inc. 相关的新闻（医药）

2022-07-13

·BioSpace

Thalassemia Market Growing at a Favorable Rate from (2021-2031): Rising Investments in the Healthcare Sector

The global thalassemia market is projected to grow at a favorable rate from 2021 to 2031 (forecast period). The expanding population, increased need for improved curative gene treatments, and increased awareness of existing treatment choices are the primary aspects expected to drive the worldwide thalassemia market during the forecast period. As per the World Health Organization (WHO), thalassemia affects around 4.4 out of every 10,000 live births worldwide. Moreover, around 5% of the world's population has a polymorphism in the beta or alpha region of the hemoglobin molecule. Furthermore, an increase in the development of pipeline pharmaceuticals and innovative therapeutics, together with research and development, is projected to boost the global thalassemia market. In addition, rising investments in the healthcare sector are likely to create revenue-generation opportunities in thalassemia market throughout the forecast period. Thalassemia Market – Competitive Landscape Leading players in the thalassemia market are Bluebird Bio, Novartis AG, Bellicum Pharmaceuticals, Acceleron Pharma, Inc., ApoPharma Inc, IONIS Pharmaceuticals, SG Pharma Pvt. Lmt, Kiadis Pharma, and Lonza Group Ltd. Market players are adopting marketing methods such as technological developments, collaborations, acquisitions, investments, and R&D activities to widen their international presence. Moreover, several innovative gene treatments with improved mechanisms of action are now in late-stage studies to meet the significant unmet demand for thalassemia therapy. GET BROCHURE OF THE REPORT Thalassemia Market – Trends and Opportunities The global thalassemia market is expected to gain from a spike in the number of clinical trials for thalassemia treatment alternatives. Moreover, the increase in thalassemia prevalence and the development of thalassemia pipeline drugs are projected to fuel the thalassemia market growth. Furthermore, factors such as the expanding market for blood transfusion therapy and bone marrow transplant, an uptick in the number of transfusion-dependent patients, and the development of accessible therapeutic solutions for thalassemia are anticipated to boost the global thalassemia market. In addition, an upsurge in healthcare spending, a rise in demand for improved curative gene therapy, and an increase in expenditure on stem cell therapy research are some of the main factors expected to promote the growth of the thalassemia market during the forecast period. The hospital segment is projected to witness significant growth in the worldwide thalassemia market during the forecast period. This is mostly due to an increase in hospital admissions for thalassemia therapy. Moreover, the increased incidence of thalassemia is expected to fuel segmental market growth. The labs segment, on the other hand, is likely to experience considerable growth during the projection period due to rising public awareness of thalassemia therapy. GET TABLE OF CONTENT OF THE REPORT Thalassemia Market – Regional Landscape The North America thalassemia market is anticipated to develop during the forecast period. The high incidence of thalassemia patients in the area, the existence of prominent players, and the developed healthcare infrastructure are some of the key reasons expected to boost the regional market growth. Moreover, positive government efforts and a rise in the number of research collaborations are likely to fuel market expansion. The United States is projected to be the largest revenue generator in thalassemia market due to increased knowledge of the disorder, a growing number of populations with the thalassemia carrier gene, and an increase in birth rates due to genetic heterogeneity within the population. The thalassemia market in Asia Pacific is likely to expand during the forecast period. The rising number of thalassemia patients and higher government spending on the healthcare system are the primary factors anticipated to propel the regional market in the upcoming years. Moreover, developing countries such as China and India are expected to contribute to the thalassemia market in Asia Pacific during the forecast period. GET DISCOUNT ON THE LATEST REPORT TMR Research has rich experience in developing state-of-the-art reports for a wide array of markets and sectors. The brilliance of the experts at TMR Research and their alacrity to conduct thorough research and create phenomenal reports makes TMR Research better than others. 5-Point Growth Formula The 5-point growth formula developed by TMR Research provides an insight to the stakeholders and CXOs about the current situation in the market. The growth formula makes the report a perfect companion for the stakeholders and CXOs. The 5-point growth formula includes the following points: Current and Future Threats Accurate Trend Analysis Regional Assessment Industrial Analogy COVID-19 Impact Current and Future Threats Along with studying the opportunities necessary for growth, threats are also an important aspect to look upon for the companies and stakeholders in a specific sector. TMR Research studies every negative aspect that will hinder the growth of a specific area of business and includes it in the report. The stakeholders and CXOs will have the benefit of assessing the threat and take the necessary steps to prevent the hindrance caused due to the threats. Accurate Trend Analysis Keeping up with the latest trends is crucial in any business or sector. While stakeholders are aware of the trends that are on the surface, TMR Researchers find trends that are deeply entrenched in the particular market or sector. The reports are constantly updated with the latest trends so that the stakeholders and CXOs can derive benefits from the trends and generate good revenues. Regional Assessment Demography forms an important part of the growth pattern of all the markets. Diving deep into the demographics enables maximum output from specific areas. The TMR Research team assesses every region and picks out the vital points that have a large impact on the growth of a market. Industrial Analogy The analysts at TMR Research conduct an all-round analysis on the competitive landscape of the market. The observations recorded by the analysts are added to the reports so that every stakeholder gets a glimpse of the competitive scenario and frame their business plans according to the situation. COVID-19 Impact The COVID-19 outbreak has changed the growth projections of numerous sectors and businesses. The analysts at TMR Research have conducted a conscientious survey on the markets after the pandemic struck. The analysts have put forth their brilliant and well-researched opinions in the report. The opinions will help the stakeholders to plan their strategy accordingly. The reports offer answers to the top 7 questions that revolve around the growth of the market What are the diverse growth parameters influencing the market? Which regions will contribute largely to the growth of the market What are the recent innovations and technological advancements in the market? What are the emerging trends across the market? How has COVID-19 affected the market? What will be the post-pandemic scenario of the market? What are the major threats that will dent the growth prospects of the market? About TMR Research TMR Research is a premier provider of customized market research and consulting services to business entities keen on succeeding in today’s supercharged economic climate. Armed with an experienced, dedicated, and dynamic team of analysts, we are redefining the way our clients’ conduct business by providing them with authoritative and trusted research studies in tune with the latest methodologies and market trends. Contact: Rohit Bhisey TMR Research, 3739 Balboa St # 1097, San Francisco, CA 94121 United States Tel: +1-415-520-1050 Visit Site: Also, Check Trending, TMR Research Reports – Gene Editing Market - Global Industry Analysis, Size, Share, Growth, Trends and Forecast 2021 - 2031 Point Of Care Diagnostics Market - Global Industry Analysis, Size, Share, Trends, Analysis, Growth, and Forecast 2021 - 2031 Pharmacovigilance Market - Global Industry Analysis, Size, Share, Trends, Analysis, Growth, and Forecast 2021 - 2031 Biotechnology Market - Global Industry Analysis, Size, Share, Trends, Analysis, Growth, and Forecast 2021 - 2031 Dermatology Diagnostic Devices and Therapeutics Market - Global Industry Analysis, Size, Share, Trends, Analysis, Growth, and Forecast 2021 - 2031

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100 项与 ApoPharma, Inc. 相关的转化医学

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