Imara's IMR-687 is an oral disease-modifying treatment for sickle cell disease (SCD) and β-thalassaemia. IMR-687 is a highly selective and potent small molecule inhibitor of PDE9. Blocking PDE9 acts to increase cyclic GMP levels, which is associated with reactivation of foetal haemoglobin, or HbF, a well-established modifier of disease severity. Having received Orphan Drug Designation by the FDA for IMR-687 for treatment of β-thalassaemia earlier in the year (June 2020 press release), Imara announces dosing of the first β-thalasaemia patient in the Forte Phase 2b clinical trial (NCT04411082). Multiple preclinical studies show that treatment with IMR-687 enhances both the maturation and production of red blood cells in β-thalassaemia. This is exciting news towards the development of β-thalassaemia therapeutics as there are currently no approved oral therapies to increase HbF in β-thalasaemia. Read more on Imara's press release.

Bluebird's LentiGlobinTM for sickle cell disease (SCD) gene therapy (bb1111) was granted eligibility to the Priority Medicines (PRIME) program by the European Medicines Agency (EMA). LentiGlobinTM is an investigational therapy. PRIME provides early and enhanced scientific and regulatory support to medicines that have the potential to significantly address patients’ unmet medical needs. Clinical data from the completed Phase 1/2 HGB-205 study, the ongoing Phase 1/2 HGB-206 study and ongoing long-term safety and efficacy follow-up study LTF-303 supported the PRIME application for LentiGlobinTM for SCD. The U.S. FDA granted orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation and rare pediatric disease designation for LentiGlobinTM for SCD. LentiGlobinTM for SCD also received orphan medicinal product designation from the European Commission for the treatment of SCD. For more information, see here.

CTX001™ (CRISPR Therapeutics and Vertex Pharmaceuticals) has received Priority Medicines (PRIME) designation from the European Medicines Agency (EMA) for the treatment of sickle cell disease (SCD). PRIME provides early and enhanced scientific and regulatory support to medicines that have the potential to significantly address patients’ unmet medical needs. CTX001™ is an investigational gene-editing cell therapy that uses the CRISPR-Cas9 gene-editing tool to modify patient-derived stem cells to express foetal haemoglobin (HbF). An increase in HbF levels has the potential to alleviate transfusion requirements for severe thalassaemia patients and reduce painful and debilitating sickle crises for SCD patients. CTX001 is currently the most advanced gene-editing approach in development for thalassaemia and SCD. To date, CTX001 has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, and Orphan Drug designations from the U.S. Food and Drug Administration (FDA), and Orphan Drug Designation from the European Commission, for both transfusion-dependent thalassaemia and SCD.
For more information about the clinical trials and the gene-editing process, see here.

The Sickle Cell Disease (SCD) Implementation Consortium (SCDIC) was created to address the gap in the implementation of evidence-based interventions for SCD into clinical care and to develop a longitudinal registry of patients with SCD. The SCDIC is a cooperative research program composed of eight academic/clinical sites and one data coordinating center, and is supported by the National Institutes of Health through the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute on Minority Health and Health Disparities (NIMHD). An article published in the July 15 issue of the Orphanet Journal of Rare Diseases describes the development of the SCDIC Registry, making available the registry baseline for SCD and first follow-up data collection forms and REDCap data dictionary for other SCD research efforts. Source: OJRD


The FDA granted Rare Pediatric Disease (RPD) designation for EDIT-301 (Editas Medicine, Inc.), an experimental, autologous cell medicine intended for the treatment of sickle cell disease (SCD). EDIT-301 comprises sickle patient haematopoietic stem/progenitor cells (HSPCs) that are genetically modified using a highly specific and efficient CRISPR/Cas12a (also known as Cpf1) ribonucleoprotein (RNP) to edit the γ-globin gene promoter region in the beta-globin locus. Red blood cells (RBCs) derived from EDIT-301 HSPCs demonstrate a sustained increase in foetal haemoglobin (HbF) production, which inhibits polymerisation of sickle haemoglobin (HbS) in RBCs, a hallmark of SCD, and has the potential to provide long-term treatment benefits for people living with SCD. The Company expects to file to the FDA for Investigational New Drug (IND) for SCD by the end of 2020. Source: ASH News