MGTA-456, Magenta Therapeutics’ candidate stem cell therapy, continues to show promise for stabilizing neurological function and resolving brain inflammation in patients with cerebral adrenoleukodystrophy (cALD), six-month follow-up data from two patients show.
The updated results of Magenta’s ongoing Phase 2 trial (NCT03406962) were presented at the 2019 American Academy of Neurology (AAN) Annual Meeting, held recently in Philadelphia, by Ashish Gupta, MBBS, MPH, researcher and professor at the University of Minnesota.
The poster, which highlighted data from the first five patients enrolled in the trial, was titled “Patients with Inherited Metabolic Disorders (IMD) transplanted with MGTA-456, a CD34+ Expanded Cell Therapy Product, Show Rapid Engraftment in Preliminary Phase 2 Trial.”
Magenta’s MGTA-456 is a first-in-class allogenic hematopoietic stem cell therapy (HSCT). That means patients receive a transplant of healthy blood-forming, or hematopoietic stem cells (HSCs), from a genetically identical donor (allogenic), to replace their own diseased cells.
The benefit of the therapy for ALD is thought to result mainly because the donor HSCs will give rise to healthy microglia cells — specialized immune cells of the central nervous system (brain and spinal cord). This happens because HSCs are the progenitors, or originators, that give rise to all immune cells, as well as to red blood cells and platelets.
A stem cell transplant is the only treatment option currently available with the potential for arresting ALD progression, but one of its major caveats is the need for a high number of stem cells.
MGTA-456 was designed to tackle precisely this problem, and deliver a higher dose of HSCs, well-matched to the patient, for the transplant. The product expands cord blood stem cells out of the body, in the laboratory, delivering increased stem cell numbers compared with other standard methods, according to Magenta.
The candidate therapy is expected to improve the transplant success of the new blood-forming cells. Such improvement also would reduce the risk of prolonged neutropenia, or low neutrophil counts (a type of immune cell), or low platelet levels.
Preliminary data from Magenta’s ongoing Phase 2 trial showed that patients treated with MGTA-456 recovered their neutrophils faster, showing neutropenia for only one day compared with a median of eight days of low counts for conventional transplants.
The trial is testing MGTA-456 in patients with inherited metabolic disorders (IMD), including cALD, with the primary goal of determining engraftment success. It also is assessing the therapy’s safety and tolerability.
From the targeted enrollment of 12 patients, five — two of them with cALD — have already been treated with MGTA-456.
The updated results presented at AAN showed that both cALD patients had a successful and robust cell engraftment — measured by absolute neutrophil counts — by six months following the transplant. Both also showed stable neurological function since the transplant, suggesting that the progression of the disease was arrested.
Further, the Loes score — a way to quantify disease severity based on brain abnormalities and mass loss seen on MRI scans — also remained unchanged in both patients.
Gadolinium-enhancing lesions on the MRI, a mark of brain inflammation, were resolved by one month post-transplant, with that resolution persisting through the six-month period analyzed.
According to the company, further updates on this trial — which continues to recruit patients at University of Minnesota — are expected before the end of the year.
“We are very pleased to see signs of durable disease benefit in patients with cALD,” John Davis, MD, Magenta’s chief medical officer, said in a press release.
“cALD is a rapidly progressive disease, and patients whose disease progresses quickly typically have poor long-term outcomes. The stable neurological function score and persistent decrease in brain inflammation in these two patients suggest that we have halted the inflammatory process associated with the disease which may provide long-term benefits,” Davis added.
Another presentation at AAN featuring preclinical data on MGTA-456 was titled “MGTA-456, A First-in-Class Cell Therapy, Enhances Speed and Level of Human Microglia Engraftment in the Brains of Transplanted Mice.” It was presented by Kevin Goncalves, PhD, from Magenta.
This second presentation demonstrated that the high stem cell dose delivered by MGTA-456 speeds up and increases engraftment efficacy of human microglia in the brains of transplanted mice.
