Magenta stem cell transplant drug seems to work, but is it safe?

Magenta’s stem cell therapy MGTA-456 met efficacy targets in the first few patients enrolled in a phase 2 trial to be presented at ASH next month, but with a question about safety.

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.

The safety concern is that both of the Hurler’s patients developed autoimmune cytopenia; one died from the complication and the other is still undergoing treatment. The company says however that, based on feedback from a meeting yesterday with scientific leaders in the field, it believes the fatality wasn’t related to MGTA-356.

Nevertheless, as the autoimmune reactions were seen in subjects under 2 years of age, Magenta has decided to limit future enrollment to patients above that age bracket. All told, the trial is expected to recruit 12 subjects in total.

“Blood stem cell transplantation remains the standard of care for inherited metabolic disorders, which if untreated are generally progressive and lethal, [but] remains a difficult and complex procedure,” said the MGTA-456 trial’s lead investigator Paul Orchard, M.D., a specialist in IMDs based at the University of Minnesota, in a release. “Many patients experience significant and life-threatening complications, such as dysregulation of the immune system following transplantation, including the emergence of antibodies to components of the blood system.” The two reactions also fit the known pattern that these reactions tend to occur in younger patients.

Shares in the company—which was one of our 2017 Fierce 15 companies—wobbled after the ASH abstracts were posted online as investors tried to gauge the significance of the autoimmune reaction and were down fractionally at the time of writing.

Magenta’s recently appointed chief medical officer, John Davis, M.D., who joined the company from Pfizer in February ahead of its $100 million IPO, said that it's been shown that larger doses of stem cells lead to more successful HSCT outcomes, and the company is determined to press on with its development plans for the therapy. A phase 2 study of MGTA-456 in patients with sickle cell disease is planned for the first half of 2019, while an investigator-led phase 2 study in blood cancers could start before the end of the year.