Bluebird bio announced the temporary suspension of its clinical studies of LentiGlobin gene therapy (autologous CD34+ cells encoding βA-T87Q-globin gene) for sickle cell disease (SCD) (bb111) after receiving reports of a suspected unexpected serious adverse reaction (SUSAR) of acute myeloid leukemia (AML). This is the second patient with SCD, also treated with LentiGlobin, to be diagnosed with AML in a short period of time. These reports are currently under investigation and no link to the LentiGlobin gene therapy has been yet established. Although no cases of hematologic malignancy have been reported in any patient treated with the LentiGlobin gene therapy for transfusion-dependent β-thalassaemia (licensed as ZYNTEGLO in the European Union and the United Kingdom), but since it is the same BB305 lentiviral vector used in the LentiGlobin gene therapy for SCD, the company also temporarily suspended marketing of its authorized gene therapy ZYNTEGLO while the AML case is assessed. More info: Bluebird bio press release

Genomics and Personalized Medicine for all through Artificial Intelligence in Haematological Diseases (GenoMed4ALL) is a joint initiative selected and granted by the European Commission under the Horizon 2020 Research and Innovation programme. GenoMed4All will develop a secure and private data sharing platform based on Federated Learning for the pooling of genomic, clinical data and other high-throughput data. The ultimate goal is to unleash the power of novel Artificial Intelligence (AI) models to advance research in personalised medicine for haematological diseases, combining already-established clinical-pathological parameters with advanced genomic profiling to create innovative diagnostic, prognostic and therapeutic strategies.

GenoMed4All will develop 3 application cases covering common and rare oncological (Myelodysplastic syndromes and Multiple Myeloma) and non-oncological (Sickle Cell Disease) haematological diseases. AI solutions will be implemented to enhance the diagnostic capacity, assess treatment options and predict disease outcomes. GenoMed4All’s Federated Learning will seize the power of High Performance Computing facilities and key EU networks like ERN-EuroBloodNet, pooling resources from hospital registries, data processing tools, and pre-existing repositories to support clinical research and decision making. 

GenoMed4All, coordinated by Universidad Politécnica de Madrid, will span 4 years and mobilize a large consortium of 23 key partners from Spain, Italy, Germany, France, Cyprus, Greece and Denmark, covering the whole value chain of clinical, regulatory and ethics research, academia, healthcare, disruptive tech and digital service providers. The ITHANET Portal participates in GenoMed4All and will be a key data contributor.

More information: GenoMed4All press release

CSL889 (CSL Behring) was granted orphan drug designation from the European Commission and the U.S. FDA Office of Orphan Products Development for the treatment of sickle cell disease (SCD). CSL889 is an investigational, plasma-derived hemopexin for the treatment of acute vaso-occlusive crisis (VOC), a common painful complication of SCD. Hemopexin scavenges free heme from the vasculature, conferring protection against inflammation and oxidative stress. Hemopexin levels are often depleted in SCD patients and low levels of hemopexin have been associated with increased risk for acute VOCs. An open-label Phase 1 clinical study has been initiated to assess key safety and pharmacokinetic variables of CSL889 (NCT04285827). Enrollment is currently open at two treatment sites in the U.K. More info: CSL Behring press release

The European Medicines Agency (EMA) has recently granted the designation of orphan drug to two pharmaceutical agents for the treatment of sickle cell disease (SCD); FT-4202 (Forma Therapeutics) and ARU-1801 (Aruvant). FT-4202 is a novel selective red blood cell (RBC) pyruvate kinase-R (PKR) activator designed to be a disease-modifying therapy for the treatment of SCD. The end result of this therapy is to increase haemoglobin levels in order to improve RBC health and function, and to decrease painful vaso-occlusive crises. Forma is currently enrolling patients with SCD in a randomized, placebo-controlled, multi-center Phase 1 study to evaluate the safety and pharmacokinetics/pharmacodynamics (PK/PD) of FT-4202 (NCT03815695), and plans to initiate a global registrational Phase 2/3 trial with FT-4202 in the first quarter of 2021. ARU-1801 is an investigational lentiviral gene therapy that aims to restore normal RBC function through increased levels of foetal haemoglobin in adult patients. Preliminary clinical data from the Phase 1/2 MOMENTUM study demonstrates that ARU-1801 can achieve durable reductions in disease burden with a reduced intensity conditioning regimen. The FDA previously granted Orphan Drug and Rare Pediatric Disease Designations to both FT-4202 and ARU-1801 for the treatment of patients with SCD. More info: Forma press release, Aruvant press release

Novartis announced the approval of Adakveo (crizanlizumab) from the European Commission (EC), on the 30th of October 2020. Adakveo, is the first targeted sickle cell disease therapy for the prevention of recurrent vaso-occlusive crises (VOCs), or pain crises, in patients with sickle cell disease aged 16 years and older available for use in Europe. It can be given as an add-on therapy to HU/HC or as monotherapy in patients for whom HU/HC is inappropriate or inadequate. Clinical data showed that use of Adakveo led to a significant reduction in the rate of VOCs and decrease the duration of hospitalization. VOCs disrupt patients’ lives physically, socially, emotionally and can increase risk of organ damage and early death. Therefore, preventing the sudden, unpredictable and life-threatening VOCs is hugely important, said Kees Roks, Head Region Europe, Novartis Oncology, emphasizing the importance of Adakveo approval from EC. Adakveo, is now approved in 36 countries around the world including the United States and European Union member states For more information, see here.