The European Rare Blood Disorders Platform (ENROL) conceived in the core of ERN-EuroBloodNet to serve as an umbrella for both new and already existing registries on rare haematological disorders (RHD), has officially started June 1st, 2020. ENROL online kick-off meeting was successfully held last July 2nd with more than 120 registered participants, including ERN-EuroBloodNet members, affiliated partners, candidates, EURORDIS and patients’ representatives, European Hematology Association (EHA) representatives, researchers and registries’ curators. The meeting started with a welcome and overview of ENROL from the platform coordinator followed by two blocks of presentations highlighting ENROL implementation by the different tasks leaders and the involvement of the different stakeholders as fundamental pillars for the successful implementation of ENROL, including patients, hospitals’ CEOs and the legal and ethical teams. For more information, the main outcomes of the meeting and the slides presented are available here.

FT-4202 (Forma Therapeutics Inc.) has been given Fast Track designation by the U.S. Food and Drug Administration (FDA) as a potential disease-modifying therapy for pediatric patients with sickle cell disease (SCD). FT-4202 is a novel, oral, once-daily pyruvate kinase-R (PKR) activator with a favorable tolerability profile and favorable pharmacokinetic/pharmacodynamic effects in an ongoing Phase 1 clinical trial in patients with SCD (NCT03815695). PKR is a key metabolic enzyme in energy production and has an important role in maintaining the health of red blood cells (RBCs). In SCD, reduced PKR activity leads to accumulation of 2,3-diphospho-glycerate (2,3-DPG), a byproduct of cellular metabolism that decreases the ability of haemoglobin to bind oxygen, thus favoring polymerization of deoxy-HbS - a hallmark of SCD. By increasing PKR activity, FT-4202 is thought to lower the levels of 2,3-DPG, potentially increasing haemoglobin oxygen affinity and reducing the sickling of RBCs. FT-4202 effects are anticipated to increase haemoglobin levels (lessening anaemia) and reduce the frequency of painful vaso-occlusive crises. Forma Therapeutics plans to start a global Phase 2/3 study in SCD patients later this year. Source: Sickle cell disease News, TIF.

REBLOZYL® (Luspatercept) has been approved by the European Commission for the treatment of transfusion-dependent anaemia in adult patients with beta-thalassaemia and myelodysplastic syndromes (MDS). Originally developed by Acceleron as ACE-536 and licensed by Celgene (now part of US pharma major Bristol-Myers Squibb) in 2011, REBLOZYL® was approved by the FDA for anaemia associated with beta thalassaemia last year. The approval for REBLOZYL® is based on positive data from the BELIEVE (beta-thalassaemia) and phase III MEDALIST (MDS) studies. This is the first and only erythroid maturation agent to be approved in the European Union, which, for the first time, will help decrease the number of blood transfusions and consequent iron-induced dysfunction by decreasing the iron-loading burden. For more information, see here.

IMARA Inc, announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for IMR-687 for the treatment of patients with β-thalassemia. The Orphan Drug Designation for IMR-687 was previously granted for the treatment of patients with sickle cell disease (SCD). IMR-687, is an oral, once-a-day, potentially disease-modifying treatment for SCD and β-thalassemia. It is a highly selective and potent small molecule inhibitor of PDE9 that has a multimodal mechanism of action that acts primarily on red blood cells and has the potential to act on white blood cells adhesion mediators and other cell types that are implicated in SCD. Blocking PDE9, HbF levels in red blood cells increased, improving symptomology and lowering disease burden in patients with SCD and β-thalassemia. Based on preclinical data, IMARA stated that IMR-687 has several features that make it an optimal therapeutic for SCD and β-thalassemia such as a highly potent PDE9 inhibitor, differentiated selectivity and tolerability profile, minimal brain penetration and drug product stability. More information can be found here.

Agios Pharmaceuticals, Inc, presented the updated results from the Phase 2 thalassemia in an oral presentation at the European Hematology Association (EHA) Annual Congress. The ongoing, open-label Phase 2 study is evaluating the efficacy, safety, pharmacokinetics and pharmacodynamics of mitapivat treatment in adults with non-transfusion-dependent α- and β-thalassemia who have a baseline hemoglobin (Hb) concentration of ≤10 g/dL. The trial is fully enrolled with 20 patients and includes a 24-week core period followed by a 2-year extension period for eligible participants. All patients were treated with an initial dose of mitapivat 50 mg twice daily followed by a dose-level increase to 100 mg twice daily at the week 6 visit based on safety evaluations and Hb concentrations. Treatment with Mitapivat induced Hb increase of ≥1.0 g/dL from baseline in 12 of 13 (92%) evaluable patients, including 4 of 4 (100%) α-thalassemia patients and 8 of 9 (88.9%) patients with β-thalassemia, during weeks 4-12. Sever of 8 (88%) β-thalassemia patients achieved sustained primary and Hb response in ≥2 assessments during weeks 12-24. Furthermore, preliminary results for markers of hemolysis and erythropoiesis demonstrated improvements that were consistent with the Hb increase. “Our focus now is to advance the development of mitapivat for these patients as quickly and efficiently as possible. By the end of the year, we expect to finalize a robust pivotal development plan that spans both α-and β-thalassemia, as well as transfusion dependent and non-transfusion dependent patients, with a goal of initiating a pivotal program in 2021” said Chris Bowden, chief medical officer at Agios. More information can be found here.