FDA grants CAR T-cell therapy Descartes-08 its RMAT designation – Myasthenia Gravis News

Cartesian Therapeutics investigational cell therapy Descartes-08 has been granted regenerative medicine advanced therapy (RMAT) designation by the U.S. Food and Drug Administration (FDA) for the treatment of myasthenia gravis (MG).

RMAT status is intended for experimental regenerative medicines to treat, modify, reverse, or cure a serious or life-threatening disease and which have shown preliminary clinical evidence of being able to address an unmet need for treating that disease.

Developers of RMAT-designated treatments receive all the incentives of fast track and breakthrough therapy designations, including early and intensive interactions with the FDA that can help hasten treatment development.

Descartes-08 has also been granted orphan drug designation by the FDA for MG, another status intended to speed the therapys development by offering regulatory support and financial incentives.

Receipt of RMAT designation underscores our belief that Descartes-08 could serve as a meaningful addition to the MG treatment landscape, Carsten Brunn, PhD, president and CEO of Cartesian, said in a company press release.

We look forward to working closely with the FDA to efficiently advance the development of Descartes-08 for this underserved population, Brunn added.

Meanwhile, Descartes-08 is being tested in MG patients in a Phase 2b clinical trial, called MG-001 (NCT04146051). Cartesian remains on track to announce top-line results from the study by mid-year.

MG, an autoimmune disease, is caused by self-reactive antibodies that attack healthy proteins residing at the site of communication between nerve and muscle cells. These antibodies are produced by certain types of immune B-cells.

Descartes-08 is designed to deplete the levels of these B-cells, thereby lowering the production of disease-driving antibodies and easing MG symptoms.

Immune T-cells have the means to kill off these B-cells, but they dont naturally know they should target them. With Descartes-08, T-cells are removed from a patients body and engineered in the lab to be equipped with a chimeric antigen receptor, or CAR, that specifically binds to a protein found on immune B-cells, called BCMA. When the modified T-cells are infused back into the patient, they are now equipped to specifically bind and destroy the harmful B-cells.

While the concept of CAR T-cell therapy for treating autoimmune diseases isnt new, Descartes-08 takes a unique approach to help avoid toxicity-related safety issues that are common with this type of therapy.

With most CAR T-cell therapies, the CAR is introduced by providing T-cells with DNA that encodes its production. While having the advantage of being a one-time treatment, this also requires that patients undergo chemotherapy to kill off existing immune cells before the treatment, leading to toxicity-related side effects.

Instead of delivering DNA, Descartes-08 delivers RNA, an intermediate molecule thats produced when converting the information in DNA to a working protein. While this RNA-based version requires repeat dosing, it also avoids the need for chemotherapy and is thought to have a better safety profile. That also means it can be administered as an outpatient procedure without hospital admission.

The MG-001 trial included Phase 1b, Phase 2a, and Phase 2b parts, all involving adults with generalized MG (gMG). After an initial Phase 1b dose-finding portion, 11 gMG patients were enrolled in the Phase 2a study. There, they were assigned to receive six into-the-vein infusions of Descartes-08 in various dosing schedules.

Across both the Phase 1b and Phase 2a parts, the treatment was well tolerated and not associated with side effects common with DNA-based CAR T-cell therapies, including neurotoxicity and cytokine release syndrome, both of which are serious types of immune responses.

Evidence of clinically meaningful improvements in measures of MG disease severity were observed among Phase 2a participants that persisted for months after the six-week treatment period ended in most patients. Levels of disease-driving antibodies in the bloodstream were also reduced.

In the ongoing Phase 2b study, up to 30 adults with gMG will be randomly assigned to receive six weekly doses of Descartes-08 or a placebo. The groups will then be switched, with those initially given Descartes-08 receiving a placebo and vice versa.

The main goal of this part of the trial is to compare the effects of Descartes-08 versus a placebo on a standard measure of patient-reported disease severity.

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FDA grants CAR T-cell therapy Descartes-08 its RMAT designation - Myasthenia Gravis News