The Chinese company that originally created a CAR-T for multiple myeloma now under clinical development by Johnson & Johnson is planning to go public, as J&J looks into the cell therapy’s potential as an outpatient treatment.
In a regulatory filing Wednesday, Nanjing-based Legend Biotech said it would seek to raise $100 million in an initial public offering, whereby its shares would trade on the Nasdaq under the ticker symbol LEGN. Data from the Phase Ib/II CARTITUDE-1 trial of the therapy, JNJ-4528, which J&J is running in the U.S. and Japan, were included in an abstract posted ahead of the American Society of Clinical Oncology’s online annual meeting. The data will be presented in an oral session at the virtual conference, which kicks off near the end of this month.
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J&J and Legend’s partnership for the CAR-T dates back to December 2017.
The abstract provided an update from data presented at the American Society of Hematology meeting in December, which showed all 29 patients in the Phase Ib portion of the study responding to treatment, with 76% achieving a stringent complete response, or sCR, along with 21% achieving a very good partial response (VGPR), and a single patient achieving a partial response (PR). At a median nine months of follow-up, 90% of patients had remained progression-free.
Meanwhile, as shown at ASH, 93% of patients experienced cytokine release syndrome (CRS). While 86% of patients experienced mild to moderate CRS, one patient experienced the side effect at a level considered severe, and another died from it. Nevertheless, the ASCO abstract concluded that CRS was manageable and opened the possibility for outpatient treatment. Notably, while CRS tends to arise quickly with other CAR-Ts – for example mostly in 1-2 days among most patients for competitors Bristol-Myers Squibb and bluebird bio’s idecabtagene vicleucel – median time to onset with JNJ-4528 was seven days. Both CAR-Ts work by targeting BCMA, an antigen widely expressed in multiple myeloma, and the former is currently under review for Food and Drug Administration approval.
“The way to manage CRS is patient self-monitoring,” said Mark Wildgust, vice president for oncology global medical affairs at J&J’s Janssen Research & Development division, in a phone interview. In other words, that means having patients monitor their temperature for fevers, a telltale sign of CRS. “If you start seeing it peak, return to the hospital. We have implemented that as an option in some of our studies.”
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Wildgust added that the ability of some patients to be dosed on an outpatient basis is written into the protocol for CARTITUDE-2, a Phase II study of JNJ-4528 that was launched in October. In other words, after being dosed, patients can return home and self-monitor.
The idea of CAR-Ts as outpatient therapies is not unheard of. For example, BMS’ CAR-T for non-Hodgkin’s lymphoma, lisocabtagene maraleucel, has sufficiently mild toxicity that it has been developed as a potential outpatient treatment. Historically, CAR-Ts’ side effects, especially CRS and neurotoxicity, have been severe enough that patients receiving them have had to stay in the hospital for monitoring.
In the case of the one patient in CARTITUDE-1 who died from CRS, Wildgust explained that it was in part due to underlying complications. Predicting whether it makes sense to let a patient go home versus keeping them in the hospital will depend on underlying features, he said.
“Essentially, you’ll look at the types of clinical features that suggest that patient could be sent home for that watching phase,” he said, adding that other trials will continue to explore whether outpatient use of JNJ-4528 is safe. That, he added, will probably come down to things like clinical risk factors like bulkiness of disease, how refractory patients were to prior therapies and whether they struggled when undergoing bridging therapy.
Legend had originally developed the CAR-T under the name LCAR-B38M. Wildgust noted that JNJ-4528 is “pretty much the same” as LCAR-B38M, but with a “little tweak” in manufacturing.
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