RARE Daily

Magenta and Bluebird Bio Collaborate on SCD Study

December 4, 2020

Rare Daily Staff

Magenta Therapeutics and Bluebird Bio said they have entered into an exclusive clinical trial collaboration to evaluate the utility of MGTA-145, in combination with plerixafor, for mobilization and collection of stem cells in adults and adolescents with sickle cell disease.

They said the data from this clinical trial could provide proof-of-concept for MGTA-145, in combination with plerixafor, as the preferred mobilization regimen for patients with SCD. Bluebird Bio’s experience with plerixafor as a mobilization agent in sickle cell disease aligns with Magenta’s combination therapy approach, utilizing MGTA-145 plus plerixafor with potential to achieve safe, rapid, and reliable mobilization of sufficient quantities of high-quality stem cells to improve outcomes associated with stem cell transplantation.

Sickle cell disease (SCD) is a serious, progressive and debilitating genetic disease caused by a mutation in the β-globin gene that leads to the production of abnormal sickle hemoglobin, causing red blood cells to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and painful vaso-occlusive events. For adults and children living with SCD, this means unpredictable episodes of excruciating pain due to vaso-occlusion as well as other acute complications—such as acute chest syndrome, stroke, and infections, which can contribute to early mortality in these patients.

Currently available mobilization drugs, including granulocyte-colony stimulating factor (G-CSF), a commonly used mobilization agent administered over the course of five to seven days in other transplant settings, is not used in sickle cell disease because it can trigger vaso-occlusive crises and even death in adults and adolescents. Plerixafor is used to mobilize a patient’s stem cells for collection prior to transplant and while an available treatment option, multiple cycles of apheresis and collection may sometimes be required to generate sufficient stem cells for gene therapy.

Magenta is developing MGTA-145, in combination with plerixafor, to be the preferred mobilization regimen for rapid and reliable mobilization and collection of hematopoietic stem cells (HSCs) to improve stem cell transplantation outcomes in multiple disease areas, including genetic diseases such as sickle cell disease, as well as blood cancers and autoimmune diseases.

In a recently completed phase 1 study in healthy volunteers, it showed it can rapidly and reliably mobilize high numbers of functional stem cells in a single day, without the need for G-CSF. MGTA-145 works in combination with plerixafor to harness a physiological mechanism of stem cell mobilization to rapidly and reliably mobilize HSCs for collection and transplant across multiple indications.

Additionally, stem cells mobilized with MGTA-145 can be efficiently gene-modified and are able to engraft, potentially allowing for safer and more efficient mobilization for gene therapy approaches to treat sickle cell disease and other genetic diseases.

Under the collaboration, the stem cells will be fully characterized, and Magenta will undertake preclinical studies to evaluate the ability of these cells to be gene corrected and engrafted in mouse models. The companies will co-fund the clinical trial and Magenta will retain all rights to its product candidate.

“In this initial study, we hope to establish whether the combination of plerixafor with MGTA-145 can generate appropriate CD34+ stem cells with a single round of mobilization,” said Dave Davidson, chief medical officer, Bluebird Bio. “If successful, we hope to evaluate this novel mobilization regimen with LentiGlobin to make another step forward in the treatment of patients with SCD.”


Photo: Dave Davidson, chief medical officer, Bluebird Bio

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