- Johnson & Johnson's experimental cell therapy for multiple myeloma, a type of blood cancer, eliminated signs of disease in every patient dosed in an early-stage trial, and kept most of them from progressing for at least nine months.
- Patient responses to the therapy, called JNJ-4528, improved over time, according to a presentation that researchers will be making at the American Society of Clinical Oncology's virtual meeting later this month. Two more went into remission since the last data release from the CARTITUDE-1 trial, which measured patient responses six months after treatment.
- If the J&J drug is approved, it could compete with Bristol Myers Squibb and Bluebird bio's experimental cell therapy, ide-cel, and potentially other drug candidates that aim at a key multiple myeloma target, a protein found on plasma cells. The Food and Drug Administration on Wednesday refused to accept Bristol's approval application, asking for additional manufacturing data.
As biopharma companies have sought new ways to treat blood-based cancers like leukemia, lymphoma and multiple myeloma, they have turned to the strategy of converting immune cells into precision, tumor-fighting weapons. Novartis' Kymriah and Gilead's Yescarta paved the way in leukemia and lymphoma, and for multiple myeloma, Bristol and Bluebird's ide-cel and Johnson & Johnson's JNJ-4528 are nearing market.
Both ide-cel and JNJ-4528 work on the principle that T cells can be engineered to detect a distinctive protein on diseased cells in multiple myeloma, called B-cell maturation agent, or BCMA, and then destroy them. These drugs are called chimeric antigen receptor T-cell, or CAR-T, therapies.
CARTITUDE-1 tested JNJ-4528 in 29 advanced patients who have progressed after treatment with at least three different multiple myeloma regimens. The therapy reduced or eliminated signs of diseased blood cells in every patient, with 22 having undetectable levels of tumor cells, at a median time of nine months following their treatment.
"It's not good enough in terms of the physician point of view or the patient point of view to achieve response," said Craig Tendler, J&J's vice president of oncology clinical development, in an interview. "We want it to be a deep response and a durable response, where the patient is no longer receiving therapy and hopefully has recovered from the side effects."
Those side effects include an immune response called "cytokine release syndrome," which has troubled a majority of patients who have received CAR-T. In the case of JNJ-4528, one patient died 99 days after receiving treatment and had prolonged cytokine release syndrome.
Tendler said that case had taught researchers "how to intervene earlier" with cytokine release syndrome when using JNJ-4528. Compared with patients treated with Kymriah and Yescarta, cytokine release syndrome set in later, typically after seven days, so patient monitoring needed to be designed differently.
However, he noted that the later onset of cytokine release syndrome with JNJ-4528 means it could potentially be an outpatient treatment because patients might not need immediate monitoring as with other CAR-Ts.
Bristol also had updated data on ide-cel from its KarMMA trial in a similar multiple myeloma population, in which it reduced or eliminated diseased cells in 73% of patients, with a third of patients having no detectable signs of cancer. The results were largely the same as what was released last December, but now include further follow-up.
Data from another Bristol BCMA targeting CAR-T, orva-cel, will also be featured at the ASCO meeting. It is in a Phase 1 trial.
Despite ide-cel's setback with the FDA, the drug still looks likely to reach the market before JNJ-4528, as Bristol plans to re-submit its application by the end of July. Tendler said J&J will file for approval in the second half of 2020.
Both will also go against a rival in GlaxoSmithKline's belantamab mafodotin, which combines a BCMA-targeting biological with a cancer-killing chemical. The UK-based big pharma submitted that drug to the FDA in December.
Likewise, J&J is also advancing an experimental BCMA-targeting drug that isn't a cell therapy. Called teclistamab, the so-called bispecific antibody treatment binds to both BCMA and a protein on T cells called CD3.
At ASCO, J&J will detail early data from a Phase 1 trial that showed that, at the highest dose administered, seven of nine patients saw a reduction or elimination of tumor cells.
J&J isn't alone in this approach, though. Regeneron also has a similarly acting drug in early stages of development.