Analysts appeared unfazed by the news that a patient treated with Cabaletta Bio’s autoimmune CAR-T suffered a toxicity complication during a phase 1/2 trial.
Cabaletta has been evaluating the CAR-T, called resecabtagene autoleucel or rese-cel, across six so-called RESET studies enrolling patients with autoimmune conditions like myositis, systemic lupus erythematosus, systemic sclerosis (SSc), generalized myasthenia gravis, multiple sclerosis and pemphigus vulgaris.
In its full-year earnings report, the biotech revealed that a SSc patient had experienced a grade 3-level event of immune effector cell-associated neurotoxicity syndrome (ICANS), a potentially dangerous side effect of CAR-T treatment, nine days after receiving rese-cel.
The patient's symptoms involved a “transient period of confusion,” and Cabaletta stressed in the release that the individual was “arousable throughout” with “no cerebral edema, seizures or motor dysfunction associated with the ICANS event.”
“The ICANS resolved rapidly following treatment with dexamethasone and the patient was discharged without further symptoms,” the biotech noted.
The company linked the adverse event to a failure to follow the trial protocol. Specifically, the patient had reported a fever three days before receiving rese-cel, but this information had not been passed on to the medical monitor to decide whether to proceed with the infusion.
After considering the information, the trial’s independent data monitoring committee recommended that the study “proceed at the current dose without delay” and agreed with Cabaletta’s suggestion to tighten up oversight of whether participating patients had previously had a fever.
William Blair analysts said that while news of the case of ICANS was “disappointing,” they argued it “underscores that the peri-infusion management of autoimmune disease patients is critical in minimizing the likelihood of severe safety events.”
“Furthermore, if the patient’s fever had been reported in line with the protocol and a full work-up were performed and confirmed that the infusion should be delayed until inflammatory markers normalized, we believe the event could have been prevented,” the analysts said in an April 1 note.
“Overall, we continue to view the early efficacy across multiple indications as encouraging, especially given that all patients are now off immunosuppressants and some appear to be in, or trending toward, a drug-free disease remission state,” the analysts added.
Cabaletta’s investors were less positive, however, as the biotech's stock dropped 15% over the course of Tuesday, ending the day's trading at $1.17.
Long a target for oncology, CAR-T has moved into immunology on the strength of academic research last year that showed a patient with lupus achieving remission after treatment.
Cabaletta said it is now enrolling an average of one patient a week across the RESET program, with 33 patients having received rese-cel across the trials as of March 14. The company is aiming to share clinical and translational data at the EULAR 2025 Congress in Spain in June.
“We are looking forward to meeting with the FDA to align on registrational trial designs in myositis, which affects approximately 70,000 patients in the U.S., by leveraging our emerging clinical data and our efficient development strategy,” Cabaletta CEO Steven Nichtberger, M.D., said in the earnings release.
“Since presenting clinical and translational data from the RESET program demonstrating that a single weight-based dose of rese-cel was able to provide potentially transformative clinical responses after discontinuation of all immunosuppressants and while off or tapering off steroids, we have seen robust physician and patient interest in the RESET clinical program,” Nichtberger added.