Months after announcing an M&A deal with AstraZeneca, EsoBiotec has released the first small slice of data on the cell therapy asset that attracted the Big Pharma’s attention. Four patients with multiple myeloma who received the Belgian biotech’s in vivo T-cell editing therapy all responded to treatment, with the cancer of two patients resolving completely.
The results come from EsoBiotec’s ongoing phase 1 trial in Wuhan, China, and were published in The Lancet on July 2. The trial aims to enroll up to 24 patients with relapsed or refractory multiple myeloma, a blood cancer that arises in plasma cells in the bone marrow. The four patients detailed in the paper had all been previously given at least two other treatments.
EsoBiotec uses lentivirus vectors to deliver mRNA to T cells within the body, which is meant to endow the immune cells with the tools they need to pursue and destroy cancer cells. The company’s lead and only clinical asset, ESO-T01, is designed to reprogram T cells to target B-cell maturation antigen (BCMA), which is often overexpressed by malignant blood cells in multiple myeloma.
All four patients were given a single infusion of ESO-T01 and had adverse events of varying severity, the trial researchers reported in the paper. All developed acute inflammatory reactions on the day of the infusion such as chills and fevers, and three patients developed low blood pressure that required medication.
All the patients ultimately developed cytokine release syndrome, three at grade 3 and one at grade 1, and the patient with the most cancerous tissue also developed grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS).
Other side effects included blood toxicities like neutropenia, leukopenia and thrombocytopenia, as well as lung infections.
One patient’s cancerous lesions and malignant blood cells in the bone marrow disappeared completely by day 28 after infusion, and another’s disappeared by two months after treatment. The other two patients had partial responses, with lesions shrinking and cancer cells reduced.
“In this case series, ESO-T01 appeared to eradicate extramedullary disease,” the authors wrote, referring to myeloma that has spread outside of the bone marrow. “Nevertheless, a larger cohort and longer follow-up are needed to further look into the persistence of in vivo-produced CAR T cells and their efficacy, and a randomized controlled design is required for more convincing results.”
AstraZeneca’s $1 billion entry into the in vivo CAR-T space was sparked by initial data from a single patient, presented by EsoBiotec at January’s J.P. Morgan Healthcare Conference. The total cost for the British pharma to acquire EsoBiotec is split between an upfront payment of $425 million and up to $575 million in developmental and regulatory milestones.
Lentiviral vectors like those used by EsoBiotec have sparked interest for their low toxicity and ability to infect both dividing and nondividing cells. Orchard Therapeutics’ approved metachromatic leukodystrophy therapy Libmeldy uses the vectors, as does Zynteglo, bluebird bio’s sickle cell treatment.