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

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.

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.

Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), presented positive results from its Phase 2 proof-of-concept study of the oral pyruvate kinase (PK) activator "mitapivat" for non-transfusion-dependent thalassaemia (NTDT). This is the first clinical study of a PK activator in thalassaemia and the first drug trial in α-thalassaemia. The Phase 2 trial of mitapivat evaluated its efficacy, safety, pharmacokinetics and pharmacodynamics in 20 adult patients with either α- or β-NTDT and ≤10 g/dL baseline haemoglobin (Hb) levels. A sustained increase in Hb levels ≥1.0 g/dL from baseline was reported in 80% of the treated patients, together with improvements in hemolysis and ineffective erythropoiesis, and mild adverse drug reactions similar to previous studies in healthy volunteers and patients with PK deficiency. Agios plans to initiate two Phase 3 studies of mitapivat, ENERGIZE and ENERGIZE-T, in not regularly transfused and regularly transfused adults with thalassaemia. More info: Agios press release