Bluebird bio announced it has completed the rolling submission of its Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for approval of betibeglogene autotemcel (beti-cel) gene therapy in adult, adolescent and pediatric patients with β-thalassaemia who require regular red blood cell transfusions, across all β genotypes. Beti-cel is already cleared for market in Europe, where it's sold under the brand name Zynteglo. The BLA submission for beti-cel is based on data from Phase 1/2 and Phase 3 Northstar studies, which represent more than 220 patient-years of experience with beti-cel. The FDA previously granted beti-cel Orphan Drug status and Breakthrough Therapy designation for the treatment of transfusion-dependent β-thalassemia. If approved, beti-cel will be the first hematopoietic (blood) stem cell (HSC) ex-vivo gene therapy for patients in the United States. Source: bluebirdbio press release

We are excited to announce a paper about the recently formed International Hemologlobinopathy Research Network (INHERENT), published in the American Journal of Hematology (DOI: 10.1002/ajh.26323). Through a large-scale, multi-ethnic GWAS, INHERENT (https://inherentnetwork.org) will study how genetic modifiers influence the diverse clinical manifestations and the varying degree of severity of hemoglobinopathies, including thalassemia syndromes and sickle cell disease. INHERENT brings together 9 existing international/regional consortia in the field, namely ITHANET, RADeep, ARISE, SPARCO, SADaCC, REDAC, HVP GGN, IHR and ClinGen Hemoglobinopathy VCEP, and is endorsed by the European Reference Network on rare hematological diseases, ERN-EuroBloodNet. Participation in INHERENT is open to any group that can submit a minimum of 30 samples with their core phenotypic description. The current membership includes over 170 experts from 90 organizations, spanning 36 countries worldwide. With its current membership, the network has the potential to enroll over 73 thousand patients. The goal is to enroll at least 30 thousand patients, which is over one order of magnitude larger than any previous GWAS in the field. The large increase in the sample size and the diversity in the studied populations will enable novel discoveries and expand knowledge on hemoglobinopathy genetics, thus paving the way for advancing the science of personalized diagnosis and treatment.

For more information, please visit the INHERENT official website and see the information sheet.

Global Blood Therapeutics, Inc. (GBT) announced updates across several of its development programs in sickle cell disease (SCD), on 22 of July. GBT introduced two global, randomized, placebo-controlled, pivotal Phase 3 clinical trials of inclacumab, a novel P-selectin inhibitor. Also enrolled the first SCD patient in a Phase 1 study evaluating GBT021601 (GBT601), a next-generation hemoglobin S (HbS) polymerization inhibitor, in people with SCD. Furthermore, the company has submitted a supplemental New Drug Application to the U.S. Food and Drug Administration seeking accelerated approval for Oxbryta® (voxelotor) for the treatment of SCD in children ages 4 to 11 years, together with a related separate New Drug Application (NDA) required to seek approval for a pediatric weight-based formulation of Oxbryta. President and CEO of GBT believes that the supplemental New Drug Application for Oxbryta creates a significant potential to impact the longer-term outcomes by addressing the root cause of red blood cell sickling at a young age. More info: Global Blood Therapeutics, Inc. press release.

Imara announced encouraging results from the Phase2a clinical trial on IMR-687 in 93 patients with sickle cell disease (SCD) at the EHA2021 Virtual Congress, June 9-17, 2021. IMR-687 is an oral disease-modifying treatment for SCD and β-thalassaemia that acts to reactivate foetal haemoglobin (HbF) by blocking a cGMP-selective phosphodiesterase, called PDE9.
Clinical data reported that treatment with IMR-687 at 200 mg was safe and well-tolerated as a monotherapy or in combination with hydroxyurea and, did not have treatment-related serious adverse events (mainly headache, nausea, and abdominal pain). The treatment sucessfully reduced the average annualized rate of vaso-occlusive crises (VOCs) by 40% and increased the time to first VOC by almost 2-fold compared with placebo. In addition, more than one-third (36%) of patients with SCD achieved absolute HbF increases of more than 3% at month eight with minimal change in total haemoglobin. Based on these findings, Imara launched the Ardent Phase2b clinical trial to assess the safety and clinical efficacy of IMR-687 at a higher daily dose of up to 400 mg in SCD. This trial is currently being conducted across 50 sites in 13 countries, including Africa, and patient enrollment is marked as complete. The company is currently enrolling patients for its Forte Phase 2b clinical trial of IMR-687 for β-thalassaemia. Imara recently announced that the United States Adopted Names (USAN) Council adopted “tovinontrine” as the generic name for IMR-687. For more information: ASH news, Imara press release-June, Imara press release-August

Thalassaemia International Federation (TIF) has published the 4th Edition 2021 Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT) in collaboration with editors Cappellini MD., Farmakis D., Porter J., and Taher A.  The TIF Guidelines are adopted and used extensively by academics, researchers and healthcare professionals all over the world as the only evidence-based reference text concerning the treatment of patients with TDT. The newly launched edition includes brand new chapters on the recently approved modalities of patient treatment, the value of patient engagement at the decision-making level, the Reference Centres’ contribution to patient care, and much more. You can access the publication here.