Durable reductions in MG severity seen with Descartes-08 cell therapy
Cartesian plans a Phase 3 trial to test therapy in people with AChRs antibodies
The investigational cell therapy Descartes-08 led to durable reductions in disease severity for people with myasthenia gravis (MG), according to updated Phase 2b trial results presented by Cartesian Therapeutics, its developer.
“Data reported today add to the growing body of evidence supporting the potential for Descartes-08 to provide deep and durable improvements for participants with MG,” Carsten Brunn, PhD, Cartesian’s president and CEO, said in a company press release.
Cartesian is planning for the 2025 launch of a Phase 3 trial called AURORA, which will look at Descartes-08’s ability to ease disease severity in MG patients who have antibodies against acetylcholine receptors (AChRs), the most common type of MG-causing antibodies.
“We look forward to commencing the trial during the first half of next year as we continue to work toward our mission to deliver this much-needed therapy to patients,” Brunn said.
In MG, the immune system mistakenly attacks proteins important for nerve-muscle communication. These attacks are mediated by the production of self-reactive antibodies from immune B-cells.
What is Descartes-08?
Descartes-08 is a CAR T-cell therapy that’s designed to boost the immune system’s ability to target and kill B-cells to ease disease severity.
A patient’s own T-cells — immune cells that are capable of attacking and destroying other cells — are collected and engineered in the lab with a chimeric antigen receptor (CAR), which is designed to specifically recognize a protein on the surface of B-cells called B-cell maturation antigen. When the engineered T-cells are infused back to the patient, the CAR will direct them to bind to B-cells and launch an attack.
Most conventional CAR T-cell therapies use DNA to introduce a CAR into T-cells, which requires that patients undergo chemotherapy to clear out existing immune cells and make room for the engineered ones.
Descartes-08 instead uses messenger RNA, an intermediate template molecule normally used by cells to make proteins. This enables the therapy to be given without chemotherapy and avoids some of the side effects seen with conventional CAR T-cell therapies. Cartesian expects Descartes-08 can be safely given as an outpatient procedure.
The Phase 1/2 MG-001 trial (NCT04146051) was designed to test Descartes-08 in people with generalized MG (gMG).
Results of Phase 2b study
In its Phase 2b part, 36 patients were assigned to receive weekly infusions of Descartes-08 or a placebo for six weeks and were monitored for about three months.
A significantly higher proportion of those given Descartes-08 achieved a clinically meaningful reduction in disease severity, as assessed by changes in MG Composite scores, after three months compared with a placebo (71% vs. 25%), meeting its main goal.
The treatment led to similar clinical improvements in the subgroup of patients positive for AChR antibodies, in addition to lowering the levels of such antibodies in the blood.
In the recent update, Cartesian reported that deepening clinical responses were observed in the participants over time.
The average improvement in the scores of the MG Activities of Daily Living (MG-ADL) scale, another validated measure of disease severity, after four months was 5.5 points for 12 people with available data. A score reduction of at least 2 points is considered clinically meaningful.
These responses further deepened after six months, when a third of the participants with available data had minimum symptom expression, or an MG-ADL score of 0 or 1. Particularly strong responses were observed in those without prior exposure to biologic therapies — an average MG-ADL reduction of 6.6 points after four months. Nearly 60% of these participants had minimum symptom expression after six months.
The responses were sustained through a year, with four of five participants with evaluable data maintaining a clinically meaningful MG-ADL response.
“These updated results continue to show deep responses durable for months after cessation of treatment … underscoring the potential for Descartes-08 to emerge as a meaningful addition to available MG treatments,” said James F. Howard, MD, the trial investigator and professor at the University of North Carolina School of Medicine.
Descartes-08 was well tolerated with no reported cases of types of severe immune responses usually seen with conventional CAR T-cell therapies.
In the Phase 2a portion, seven gMG patients received a six-week course of Descartes-08, which led to durable clinical improvements. Three of them have since received a second six-week treatment cycle, with data showing similar clinical responses as those observed after the first treatment cycle.
“We believe these updated results align well with the endpoints of our planned Phase 3 trial, strengthening our confidence in the design of the next phase of Descartes-08’s development,” Brunn said.
AURORA will enroll 100 people with AChR antibody-positive MG, who will be randomly assigned to receive a six-week course of Descartes-08 or a placebo. The main goal is to evaluate the proportion of patients who achieve at least a 3-point improvement in MG-ADL scores after four months. Safety and other measures of disease severity will also be evaluated.
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