A phase 3 trial study published in the June 1 issue of The Lancet of Haematology evaluating the efficacy and safety of deferiprone compared with deferasirox in paediatric patients with transfusion-dependent haemoglobinopathies (DEEP-2). Maggio A. and colleagues show the the non-inferiority of deferiprone versus deferasirox. DEEP-2 was a phase 3, multicentre, randomised trial in paediatric patients (aged 1 month to 18 years) with transfusion-dependent haemoglobinopathies. The study was done in 21 research hospitals and universities in Italy, Egypt, Greece, Albania, Cyprus, Tunisia, and the UK. Participants were receiving at least 150 mL/kg per year of red blood cells for the past 2 years at the time of enrolment and were receiving deferoxamine or deferasirox. Between March 17, 2014, and June 2016, 393 of the 435 patients were randomly assigned to a treatment group (194 to the deferiprone group; 199 to the deferasirox group). Non-inferiority of deferiprone versus deferasirox was established and compliance was similar between treatment groups: 183 (95%) of 193 patients in the deferiprone group versus 192 (97%) of 197 patients in the deferisirox group.In paediatric patients with transfusion-dependent haemoglobinopathies, deferiprone was effective and safe in inducing control of iron overload during 12 months of treatment. Considering the need for availability of more chelation treatments in paediatric populations, deferiprone offers a valuable treatment option for this age group.

More information: Original publication.

The ITHANET portal has completed the submission of 288 variation-phenotype relationships to ClinVar. Specifically, the submitted variants hold asserted relationship to either α- or β-thalassaemia and spanned one or more globin genes. Importantly, 151 of the submitted variants were novel, whilst a total of 57 alleles already existing in ClinVar were annotated with a new phenotype. All ClinVar links produced by the submission have been integrated into the IthaGenes database. For more information and the records submitted to ClinVar, see here.

CTX001™ (CRISPR Therapeutics and Vertex Pharmaceuticals) has received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration (FDA) for the treatment of sickle cell disease (SCD) and transfusion-dependent β-thalassaemia (TDT). CTX001™ is an investigational gene-editing cell therapy that uses the CRISPR-Cas9 gene-editing tool to modify patient-derived stem cells to express fetal haemoglobin (HbF). An increase in HbF levels can compensate for the abnormal synthesis and function of adult haemoglobin in adult patients with SCD and TDT, and ameliorate the clinical and hematologic severity of both disorders. Preliminary data from the Phase 1/2 CLIMB-SCD-121 trial (NCT03745287), assessing the safety and effectiveness of a single dose of CTX001™ in patients 18 to 35 years of age with SCD, has shown that the therapy safely increased HbF levels and effectively prevented the occurrence of vaso-occlusice crises. Positive early findings have also been reported for the first TDT patient receiving CTX001™ in the Phase 1/2 CLIMB-Thal-111 trial (NCT03655678), for which patients are still being recruited. In addition to RMAT designation, CTX001™ has received Orphan Drug Designation from the FDA for TDT and from the European Medicines Agency (EMA) for TDT and SCD. CTX001™ has also Fast Track Designation from the FDA for both disorders. For more information, see here.

Agios Pharmaceuticals, Inc, announced that the updated results from the Phase 2 thalassemia study will be presented at the European Hematology Association (EHA) Annual Congress being held virtually June 11-14, 2020. Phase 2 trial of Mitapivat (AG-38) involves patients with non-transfusion-dependent thalassemia. Mitapivat is an investigational, first-in-class, oral, small molecule allosteric activator of wild-type and a variety of mutated pyruvate kinase-R (PKR) enzymes. The Phase 2 study has enrolled 12 (nine with β-thalassaemia and three with α-thalassaemia) of the intended 17 patients. The primary endpoint has been set as a haemoglobin increase of ≥1.0 g/dL from baseline in at least one assessment during weeks 4-12. The β-thalassaemia patients were treated with 50 mg of Mitapivat twice daily for the first six weeks and escalated to 100 mg twice daily, and all patients remain on treatment for 12.4 to 34.3 weeks. Seven of eight efficacy evaluable patients achieved a hemoglobin increase of 1.0 g/dL, and for responders the mean hemoglobin increase from baseline was 1.76 g/dL (range, 0.9–3.3 g/dL) during weeks 4-12. More information can be found here.

The Committee for Medicinal Products for Human Use (CHMP) recommended the granting of a marketing authorization for the medicinal product Reblozyl, on the 30th of April 2020. Reblozyl is a novel erythroid maturation agent, intended to treat adult patients with β-thalassaemia who require regular red blood cell transfusions. Also, Reblozyl has been approved for the treatment of adult patients with myelodysplastic syndrome (MDS). Reblozyl has the potential to decrease the number of transfusions in patients with β-thalassaemia and MDS. The European Commission will review the recommendation for this medicinal product in order to approve or not the Reblozyl in the European Union. Authorized marketing of Reblozyl in the European Union will represent a new class of therapy for adult β-thalassaemia patients who have limited treatment options. For more information, see here.