Latest J&J-partnered Legend Biotech data spotlight continued high response rate but 10 patient deaths
Legend Biotech has has a good three years ever since the then-little known biotech unveiled a round of BCMA CAR-T data at ASCO. It helped net them a partnership with J&J and, more recently, one of biotech history’s biggest IPOs.
Now, the Nanjing-based biotech unveiled their largest set of data for the therapy, showing interim results from a pivotal US study conducted with J&J. The data affirmed the drug’s now well-documented efficacy, with a 94% response rate and a 55% complete response rate, but it also revealed that, out of 97 patients in the study, 10 died.
Eight of the deaths were from adverse events — whether related or unrelated — and two were from disease progression. Notably, though, only one death was from cytokine release syndrome, the inflammatory condition that has dogged CAR-T since the first experimental therapies were put into humans.
Legend disclosed the CRS death, along with two others, in their S-1 this spring.
The company also noted a 20.6% rate of neurotoxicity, another common dangerous CAR-T side effect. After the last cut of data in 29 patients in December, they had said “neurotoxicity was infrequently observed.”
Of course, severe side effects have not always held up CAR-T treatments in the past, particularly when they also brought compelling efficacy data, and the J&J investigators said the data were “consistent” with prior studies. Novartis, for instance, saw 3 deaths in its pivotal study for Kymriah and more than half of its patients experience neurological symptoms.
Safety splits could become particularly relevant, though, as J&J seeks to go head-to-head with the rival multiple myeloma CAR-T treatment from bluebird and Bristol Myers Squibb, which is already sitting before the FDA.
In their most recent phase II data, bluebird similarly saw one CRS-related death out of 140 patients, but didn’t disclose other deaths in the trial. They reported that 3.1% of patients had grade 3 or higher neurotoxicities.
That data set also showed reduced efficacy compared to what Legend showed in today’s cut, continuing a trend since ASCO 2017. (Bluebird maintained at the time that Legend chose easier patients). They saw an 81.5% response rate in the highest performing dose group, with 35.2% seeing some form of complete response.
J&J wasn’t yet able to collect duration of response data, but they showed that one patient has responded for around 20 months. Of patients who were followed for 6 months, 87.4% had not seen their cancers progress at that time and 93.8% were still alive.