The U.S. Food and Drug Administration (FDA) has granted Magenta Therapeutics’ cell therapy MGTA-456 the Regenerative Medicine Advanced Therapy (RMAT) designation for treating inherited metabolic disorders, including cerebral adrenoleukodystrophy.
The RMAT designation is a program established to help expedite the development and approval of promising therapies. It is given to products that have preliminary clinical evidence of being able to treat, modify, or cure a serious or fatal disease, and potentially address unmet medical needs for that disease.
“This RMAT designation was based on the encouraging clinical data we have presented thus far, and it is an important milestone that recognizes the transformative, life-saving potential of MGTA-456 for children suffering from inherited metabolic disorders,” John Davis, MD, chief medical officer at Magenta Therapeutics, said in press release.
MGTA-456 is a stem cell-based therapy — specifically, allogenic hematopoietic stem cell therapy (HSCT) — designed to help stop the progression of inherited metabolic disorders. This is possible through the delivery of a high-dose of stem cells to help regenerate the patient’s immune system. The procedure requires patients to receive a transplant of healthy blood-forming cells, or hematopoietic stem cells (HSCs), from a genetically identical donor (allogenic), to replace their own diseased cells.
MGTA-456 is being developed as a treatment for multiple diseases.
The therapy is currently being evaluated by Magenta in a Phase 2 clinical trial (NCT03406962) in patients with various genetic metabolic disorders, including cerebral adrenoleukodystrophy (cALD), Hurler syndrome, metachromatic leukodystrophy, or globoid cell leukodystrophy. All participants are older than 6 months.
Previous results from the first five patients — two of them with cALD — who were followed for six months, showed a rapid and consistent benefit with MGTA-456 treatment that was not seen with other investigational therapies.
Patients with cALD, in particular, were found to have resolution of brain inflammation on magnetic resonance imaging (MRI) scans, as early as 28 days after the treatment. Additionally, patients had stable neurological function scores at six months post-treatment, suggesting that the progression of the disease was halted. The Loes score, which quantifies the severity of brain abnormalities and atrophy, also was stable at six months.
All five patients analyzed achieved the primary goal of neutrophil engraftment, in which levels of neutrophils (a type of immune cell) have reached an absolute count of 500 or more neutrophils per cubic millimeter of blood for three consecutive days. Of note, a robust neutrophil engraftment means that the transplant of the stem cells was succeeded.
Following the success of this trial, Magenta expects to present further data before the end of 2019.
“We look forward to collaborating closely with the FDA as we seek to rapidly advance MGTA-456 through the ongoing Phase 2 study, and into potential pivotal studies in 2020,” Davis said.