Gene Therapy, R&D

Bluebird, Celgene jump off to a promising start in the marathon race to develop a CAR-T for multiple myeloma

The clinical race to develop a relatively safe BCMA-targeting CAR-T for multiple myeloma is underway, and it’s starting with a preliminary Polaroid after the first few promising paces out of the gate for a handful of patients treated with bb2121 by bluebird bio $BLUE.

The biotech, partnered with myeloma powerhouse Celgene $CELG, offered up a clearly positive early snapshot showing that 7 of 9 evaluable patients responded to the therapy, with two complete responses, one nearly complete response and four partial responses indicating that more than half of their targeted precancerous cells had been eliminated. And in a field that has managed to raise repeated red flags on safety, bluebird was clearly chuffed that investigators so far had seen none of the damaging side effects that has plagued the CAR-T field from its earliest days.

Bluebird’s shares soared 27% on the news as investors bought in to a strong early start.

Gena Wang, Jeffries

Gena Wang, Jeffries

Gena Wang at Jefferies summed it up like this:

Efficacy data for bb2121 anti-BCMA CART cells was reported for the first 9 relapsed refractory multiple myeloma (R/R MM) pts in 3 dose cohorts. All 6 pts in cohort 2 (15E+7 cells) and cohort 3 (45E+7 cells) achieved responses (2 sCR and 1 VGPR in cohort 2 and 3 PRs in cohort 3). The 2 sCR sustained with 4-6 mon follow-up. The ORR in the first 9 pts was 78% (7/9). All pts received a median of 6 prior therapies including autologous stem cell transplant. Longer follow-up would be important to evaluate duration of response as well as possibility of PR converting into CR. We see the initial data as one of the best vs. other BCMA-targeting programs.

Without dose-limiting evidence of toxicity, investigators will be able to amp up the treatment, looking for a more durable response. And that could make a big difference as it weighs in against the other developers in this race, including a Penn team which is also rolling out additional data soon with preclinical efforts underway at Cellectis/Pfizer and Autolus. Juno jumped into the race in August.

Bluebird is using the same basic cell engineering approach as the clinical leaders in the field, like Kite, extracting T cells from patients and engineering them to go after a cancer target — in this case B-cell maturation antigen, a protein which is found on the surface of the targeted cells. It’s widely considered an excellent target for combatting a lethal disease.

But getting these cells to populate and multiply with a therapeutic effect in patients has been a vexing, and sometimes fatal, challenge. Early on instances of cytokine release syndrome held back early efforts, with some — very sick — patients dying in the process. Earlier this year Juno stunned investors with the news that cerebral edemas had killed four patients in two studies, forcing a very brief clinical hold that the FDA was willing to lift just a few days later after the biotech said that removing fludarabine from the preconditioning regimen would solve the neurotoxicity issue.

Then, after treating only 12 more patients, two more died of cerebral edemas. The FDA has not taken action, but Juno put the lead trial back on voluntary hold, leaving them in limbo while Kite races ahead to an accelerated filing now planned for Q1 2017.

Significantly, bluebird’s team is using a cy/flu conditioning regimen in its multiple myeloma program, once again raising questions about Juno’s judgment in restarting its controversial study. And Baird’s

Brian Skorney, Baird

Brian Skorney, Baird

Brian Skorney added a healthy note of skepticism on Thursday, observing that the CAR-T field has been roiled aplenty by unexpected setbacks along the way. He wrote:

After a series of patient deaths associated with other CAR T programs at Juno, which Celgene has an almost 10% stake in, bluebird’s Phase 1 results are even more impressive. However, we remain healthily skeptical on the CAR T space, as it remains to be seen whether these results will hold up long term and if safety issues arise.

The numbers for bluebird are small and preliminary, but in this field small and preliminary are still important milestones when you’re hoping to advance an important new way to treat multiple myeloma. Many, many more snapshots of clinical progress lie ahead. And analysts will inspect each one for every sign of success and failure.

That only happens when the stakes are high.

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Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
Director of Operations
Atlas Venture Cambridge, MA

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