BioPharma

Bluebird is pretty chirpy about its anti-BCMA CAR-T therapy results

You know you’re on to something worthwhile when your study leader can't quite hold back the tears when presented with the final data. On Monday, Bluebird Bio will share that same data at ASCO 2017.

ASCO 2017

A walkway during the 2017 ASCO annual meeting

You know you’re on to something worthwhile when your study leader can’t quite hold back the tears when presented with the final data.

That was the case with Bluebird Bio’s first major clinical trial for its experimental anti-BCMA CAR-T cell therapy in patients with relapsed and/or refractory multiple myeloma.

In an open-label Phase 1 study, 100 percent of patients taking an active dose had some sort of response to the therapy. Of those, 73 percent achieved a very good partial response or better, the company reported. The results also appear durable: One patient has now survived for more than a year and none of the patients that received the one-time active dose have shown disease progression.

According to “Chief Bluebird” (CEO) Nick Leschly and CMO David Davidson, it has been hard to keep the results under wraps. Both spoke to MedCity on Sunday at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, ahead of Monday’s data reveal.

“This data is above and beyond certainly what has previously been seen in this patient population,” Leschly remarked, stressing that life expectancy for these heavily treated multiple myeloma patients is typically measured in months. 

The therapy at hand is bb2121, a patient-specific engineered T-cell that Bluebird is co-developing with Celgene. Perhaps more than any other class of cancer treatments, CAR-T therapies such as bb2121 are a process, not a drug.

It begins with the harvesting of a patient’s white blood cells. Certain T-cells are then isolated and infected with a lentiviral vector, which carries a new piece of DNA into the nuclei of the cells. The engineered T-cells are then amplified and reinfused back into the patient.

That’s when the magic starts. With their new DNA sequence, the reintroduced T-cells are programmed to target a specific protein expressed on the surface of mature B cells, BCMA. In multiple myeloma, damaged B-cells produce damaged plasma cells, which in turn produce the deluge of M protein that characterizes the disease. There are side effects with the loss of B-cells, but it’s much better than succumbing to cancer.

Novartis, Kite Pharma, and Juno Therapeutics are also diving head first into the field. They use a similar T-cell engineering process but target different proteins and diseases. Novartis and Kite have both filed for FDA approval and are readying for a logistically-challenging commercial launch.

Juno, on the other hand, fell behind following multiple patients deaths and the subsequent termination of one of its programs. It’s a reminder for everyone that the approach is high risk.

For its part, Bluebird is quietly chugging along with one clinical and several preclinical candidates, alongside its gene therapy and gene editing work.

That’s not to say the journey has been all smooth sailing and Davidson and Leschly freely admit that they don’t always know what and why things are happening at a molecular level.

Thankfully, safety and tolerability for bb2121 have thus far exceeded the team’s expectations. The executives find themselves struggling to explain why the side effect profile is low; not why the therapy has led to patient deaths.

Having dosed 21 patients, Davidson said Bluebird has registered just two Grade 3 events. “Within 24 hours both of the Grade 3s were resolved,” he stated. “So it was very manageable.”

No Grade 3 or 4 neurotoxicity has been observed, which has been the downfall of other CAR-T programs. That’s important for the patients treated and for future applications.

With this kind of safety, “you can also contemplate, how do you treat these patients earlier?” Leschly said. “Because if you treat them earlier, you might get even better responses with even more durability.”

The adults recruited for the Phase 1 trial being presented had truly run out of options. Participants had taken between three and 14 therapies each, with at least one autologous stem cell transplant.

“This is a multiple myeloma population that has seen everything,” Leschly explained. 

According to Davidson, the next step for bb2121 will be an expansion trial treating 20-40 more patients with the dose that appeared most favorable in the Phase 1 study. They’ll also be preparing for future registration studies with partner Celgene, Leschly added. 

But they don’t want to get ahead of themselves. And sometimes, it pays to pause and reflect on certain milestones that are reached. As Leschly noted, the scientists that developed bb2121 have already made an impact.

“At minimum, they’ve changed the lives of at least 15, probably 18 patients in a fundamental way,” he said. “So you make it human pretty fast.”

To communicate to his children what those extra months (and counting) mean, Leschly marked annual holidays on a bar chart showing patient outcomes. Each line means the patient made it to another Thanksgiving, another Christmas, another Easter.

How can you not get teary-eyed, given what’s at stake?

Photo: MedCity News

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