After Juno deaths, Bluebird posts positive CAR-T safety, efficacy signals

The biotech has seen its shares boosted by the news

CAR-T biotech Bluebird Bio has released topline data for its experimental med bb2121 in heavily pretreated multiple myeloma in a small, positive study that has not shown the serious side effects and deaths associated with Juno’s recent test of a similar treatment.

The biotech launched the study, and the first test, for bb2121 in multiple myeloma (MM) back in February with Celgene (that too backs Juno) also coming on board, following up on its option for an exclusive license and handing over a $10 million payment to secure the deal.

Now, the company has posted some early data showing that in the two out of the three cohorts coming out of the phase 1, two (made up of six patients in total) saw an objective response rate (ORR) of 100%, while one saw 33%.

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The company told FierceBiotech that the first cohort was low because it was made up of a very low dose of cells. “This is a phase 1 dose finding study, and we want to be very cautious about patient safety, so we started at a low dose.” It notes that the overall rate was 78%.

“All patients in cohorts two and three with bone marrow involvement at baseline had no detectable multiple myeloma cells in their bone marrow on day 14 or beyond 6 (range: 3-10),” the company said in a statement.

Its med, an anti-BCMA CAR-T cell product candidate, was treating patients with relapsed and/or refractory multiple myeloma and are heavily pre-treated.

The biotech told me that whilst it is difficult to compare across trials, especially with small numbers, “we are certainly excited by the responses we’ve seen to date – particularly the sCRs and the two MRD-negative [minimum residual disease, meaning they had no remaining detectable trace of the cancer] patients, the latter of which is particularly unusual in this patient population.”

All CAR-T biotechs held their breath in the summer when Juno announced a string of deaths coming out of its experimental blood cancer Rocket trial. The FDA briefly halted the test, but just a few short days later, allowed it to continue, but without the use of a chemo pre-conditioning agent fludarabine, which Juno was adamant had been the main culprit for the fatalities from cerebral edema.

But then this month, two more patients died shortly after using the biotech’s new CAR-T candidate, again of cerebral edema, and the co halted rocket itself this time.

The news hit hard, sending Juno’s shares plunging, along with rival Kite Pharma and Bluebird that were tarred with the same brush, as well as some serious questions for the FDA and why it lifted the halt so quickly, and whether it could have prevented these deaths.

But when it came to safety for its med, Bluebird said that “no dose limiting toxicities” and “no grade 3 or higher neurotoxicities or cytokine release syndrome (CRS) have been observed.”

The company explained that, whilst it’s important to note that its data are still early, “we are certainly encouraged by what we’ve seen.

“It’s difficult to say exactly what the cause or causes of the Juno issues were, but we can tell you that we are pleased with what we have seen to date with our program, and we deliberately chose a CAR construct with limited tonic signaling, which we believe contributes to toxicity.”

In Bluebird’s test, patients received a conditioning regimen of cyclophosphamide and fludarabine, followed by an infusion of bb2121 anti-BCMA CAR-T cells. These cells were produced from each patient’s own blood cells, which were modified using a lentiviral vector encoding the anti-BCMA CAR.

Bluebird was giving nothing away in terms of timelines or submissions. “These are early data, and thus it’s too early to discuss further development plans,” the company tells me.

“This is the first BCMA CAR-T study conducted at numerous sites with centralized manufacturing – and this sets us up with infrastructure to quickly move forward with further study if the data continue to look good and support further development.”

In an analyst's note from Leerink, the firm said: "While we caution that that data are still somewhat immature and we hope to learn more about the responding patients' characteristics (disease burden, prior treatment, etc.) and response duration, the early results certainly justify the high level of excitement around the potential of anti-BCMA CAR-T therapy in relapsed/refractory myeloma, as several other companies including Juno, Kite and Novartis have stated plans to also develop anti-BCMA-CAR-T product candidates."

Leerink believes Bluebird is now ahead in the anti-BCMA CAR-T development game by around 1.5 years, and saw the data as generally "impressive." 

The biotech's stock jumped nearly 28% on the news after hours last night, with partner Celgene also marginally up 1.2% afterhours, after being down 3% in normal hours trading.