Magenta Therapeutics is a biotech company with a portfolio including stem cell products. Their most well known investigational drug product is an expanded umbilical cord stem cell product called MGTA-456, an “ex-Novartis” product. Magenta just released new trial data on MGTA-456, which I see as a case of good news-bad news, and investors seem to have had a similar reaction.
The company describes MGTA-456 as, “a first-in-class allogeneic stem cell therapy consisting of a single umbilical cord blood unit expanded with an aryl hydrocarbon receptor (AHR) antagonist then administered to a patient through a bone marrow transplant.” A key feature of the product is its higher cell dose. You can see an image from the company explaining the idea behind the production and use of MGTA-456.
As FierceBiotech points out, the good news from data from abstracts for the upcoming ASH meeting is that there are some signs of strong efficacy:
“MGTA-456 is an ex-Novartis therapy, based on cord blood-derived stem cells, that aims to improve the dose that can be delivered in allogeneic hematopoietic stem cell transplants (HSCT)—an important therapy for patients with inherited metabolic disorders such as Hurler syndrome who don’t have a matched donor.
By allowing a larger cell dose, MGTA-456 is intended to reduce the time it takes for white blood cell populations to recover after HSCT, which involves destruction of the bone marrow as a first step. The new data shows that using MGTA-456 cut that to one day from a historical average of around eight days.
Moreover, all five patients treated—two with Hurler syndrome and three with adrenoleukodystrophy—met the main objective of successful stem cell engraftment 42 days after the transplant, which tops historical success rates of around 32% with regular, unexpanded cord blood transplants.”
This is encouraging, but one “asterisk” here is that this is such a small group of patients (N=5) that we should be cautionary at this point. Note that Hurler Syndrome is also known as mucopolysaccharidosis type IH.
Unfortunately, the bad news here is that the two pediatric patients with Hurler syndrome both had adverse events in the form of autoimmune cytopenia in each case. One died. Magenta suggests based on feedback from “scientific leaders in the field” that the death was not necessarily related to MGTA-456, but I don’t see how they can be sure at this point. It’s reasonably possible that the allogeneic product caused the autoimmune reaction, but admittedly I’m definitely not an expert in that specific area. Further study with more patients will help clarify the risks here.
What does the future hold? Magenta is continuing with the work, will limit participation in this area to those older than the pediatric patients who had the adverse events, and also plans soon to study MGTA-456 in sickle-cell disease and possibly blood cancers.
Paul, why use allogenic blood stem cells. Can’t the patient produce genetically matched blood stem cells via iPS cells or direct transformation of skin cells into blood stem cells?
Hey Jim,
Allogeneic products have the advantage of a firm being able to make very large number of “doses” of what hopefully is exactly the same one validated product that can be used “off the shelf” so to speak for large numbers of patients. On the other hand with autologous products, every one is going to be different and require both independent production and validation every time. That requires more time and is more costly and probably raises the chance of some problem like a mutation slipping through.
Autologous has the advantage of course of being the patients’ own cells and not requiring immunosuppression. Immunosuppression by itself probably has more risks than people realize including for cancer acceleration.
It’s interesting that Japan is now so focused on allogeneic IPS cell products when so much emphasis was initially placed on the potential of IPS cells for personalized therapies.