My fingers are crossed. Again.
IMPT-514, an experimental cell therapy produced by ImmPACT Bio, has been approved by the US Food and Drug Administration (FDA) for phase 1 multiple sclerosis (MS) trials. I hope this treatment might be the next big thing for people with MS, but I know from experience that’s far from certain.
IMPT-514 is a bispecific chimeric antigen receptor T-cell (CAR-T) therapy, designed to ease MS symptoms and progression by resetting the MS patient’s immune system. It does this by collecting that patient’s T-cells and modifying them in the lab to search out B-cells carrying CD19 and CD20 proteins, proteins carried on cells associated with MS attacks. After a course of chemotherapy (said to be much less intense than that used for stem cell transplants) the modified cells are reinfused. They then locate CD19 and 20 B-cells and destroy them.
IMPT-514 seems similar to some other disease-modifying therapies
To a non-scientist like me, this procedure seems similar to some other MS therapies that have been in use for several years. Ocrevus (ocrelizumab) kills B-cells and Lemtrada (alemtuzumab) destroys both B and T-cells, with the hope that the cells will repopulate normally. The newer Kisempta (ofatumumab) also targets B-cells. But CAR-T is designed to be more precise in the cells it selects than those DMTs.
According to Jonathan Benjamin, M.D., Ph.D., chief medical officer of ImmPACT Bio, IMPT-514 has also shown the ability to cross the central nervous system’s blood-brain barrier. Benjamin says other DMTs that aim at CD20 ablation are ineffective at doing this.
IMPT-514 is also designed as a single treatment. Alemtuzumab requires two series of infusions, spaced a year a part. Ocrelizumab requires infusions every six months, indefinitely. Ofatumumab is injected monthly.
Is CAR-T the next big MS therapy?
CAR-T is being used to treat some cancers, especially leukemias and lymphomas, but it’s still too early to know its MS future. According to Jeffrey Cohen, MD, Director of the Experimental Therapeutics Program in Cleveland Clinic’s Mellen Center for Multiple Sclerosis, as reported in the June 1, 2024 issue of Neurology Live, “We’re still trying to decide the best target population and work out the relative risks and benefits. We don’t know the appropriate CAR-T dose in MS or whether to use the patient’s own CAR-T cells or an allogeneic product.”
Cohen says there are also definite safety concerns to consider. They include mild reactions to leukapheresis or chemotherapy, and more severe potential adverse events that include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
ImmPACT Bio hopes to begin a phase 1 dose escalation trial of IMPT-514 in the first half of 2025. The trial will focus on patients who have poor disease control despite treatment with high efficacy DMTs. The hope is that the experimental treatment will slow or stop their disability accumulation.
Success is far from certain
Most experimental treatments never make it as far as a doctor’s prescription pad. Between 2015 and 2020 experimental MS therapies only achieved a 27% success rate, according to information published in Bio Drugs in August 2020, with success defined as receiving approval from the FDA or the European Medicines Agency (EMA). While that percentage is almost three times the average pharmaceutical industry rate of a measly 10%, there’s still a long way to go between the start of a phase 1 trial and time an experimental treatment reaches patients, if it ever does.
Three years ago, I wondered if Bruton’s tyrosine kinase inhibitors (BTKi’s) would be the next great hope for treating MS. Similar to CAR-T, they promised to selectively target B-cells. Less than a year later there was a stumble. A phase 3 trial of tolebrutinib was put on a partial clinical hold and patient enrollment was paused in the US because a limited number of drug-induced liver injuries were diagnosed in patients in the study. In late 2023 another BTKi, evubrutinib, failed to meet the primary end points of its phase 3 study.
I’ll keep my fingers crossed for IMPT-514. I’m hoping for success, but I’m also not holding my breath.
(Photo by Dayne Topkin on Unsplash)
(This post first appeared as my column on Rare Disease Advisor.)
