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Bluebird is pretty chirpy about its anti-BCMA CAR-T therapy results
A walkway during the two thousand seventeen ASCO annual meeting
You know you’re on to something worthwhile when your examine leader can’t fairly hold back the tears when introduced with the final data.
That was the case with Bluebird Bio’s very first major clinical trial for its experimental anti-BCMA CAR-T cell therapy in patients with relapsed and/or refractory numerous myeloma.
In an open-label Phase one examine, one hundred percent of patients taking an active dose had some sort of response to the therapy. Of those, seventy three percent achieved a very good partial response or better, the company reported. The results also emerge 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 expose.
“This data is above and beyond certainly what has previously been seen in this patient population,” Leschly remarked, stressing that life expectancy for these strenuously treated numerous myeloma patients is typically measured in months.
The therapy at mitt 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 embarks 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 fresh lump 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 fresh DNA sequence, the reintroduced T-cells are programmed to target a specific protein voiced on the surface of mature B cells, BCMA. In numerous myeloma, bruised B-cells produce bruised 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 giving way to cancer.
Novartis, Kite Pharma, and Juno Therapeutics are also diving head very 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 palm, fell behind following numerous patients deaths and the subsequent termination of one of its programs. It’s a reminder for everyone that the treatment is high risk.
For its part, Bluebird is calmly 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 slick sailing and Davidson and Leschly loosely admit that they don’t always know what and why things are happening at a molecular level.
Gratefully, safety and tolerability for bb2121 have thus far exceeded the team’s expectations. The executives find themselves fighting to explain why the side effect profile is low; not why the therapy has led to patient deaths.
Having dosed twenty one patients, Davidson said Bluebird has registered just two Grade three events. “Within twenty four hours both of the Grade 3s were resolved,” he stated. “So it was very manageable.”
No Grade three or four neurotoxicity has been observed, which has been the downfall of other CAR-T programs. That’s significant 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 one trial being introduced had truly run out of options. Participants had taken inbetween three and fourteen therapies each, with at least one autologous stem cell transplant.
“This is a numerous 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 one investigate. T hey’ll also be preparing for future registration studies with fucking 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 influence.
“At minimum, they’ve switched the lives of at least 15, most likely eighteen patients in a fundamental way,” he said. “So you make it human pretty prompt.”
To communicate to his children what those extra months (and counting) mean, Leschly marked annual holidays on a bar chart displaying 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?
