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

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

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.

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.

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.

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