- Updated results from a small, early-stage study of Bluebird bio and Celgene's CAR-T treatment reinforced its status as a promising treatment for very sick multiple myeloma patients — in turn offering reassurance it could succeed in more advanced clinical testing.
- Data presented Friday showed treatment with the BCMA-targeting bb2121 led to a median progression-free survival of 11.8 months among those patients who received an active dose of the cell therapy, many of whom had progressed after trying multiple other drugs. Of the 22 patients who received infusions of greater than 150 million CAR-T cells, 95.5% experienced a response, for a median duration of 10.8 months.
- On safety, 63% of the 43 infused patients experienced cytokine release syndrome (CRS), an adverse immune reaction common with CAR-T therapy. Yet most of these cases weren't serious, and the two that were proved controllable, according to lead investigator Noopur Raje. Median duration of CRS was six days.
Two CAR-T cell therapies are commercially available in the U.S., marketed respectively by Novartis and Gilead Sciences for treatment of leukemia and lymphoma patients. Bluebird bio and partner Celgene hope to follow that lead, having advanced bb2121 last year into a pivotal Phase 2 study called KarMMa.
The early-stage results presented Friday at the annual meeting of the American Society of Clinical Oncology (ASCO) are an important update on how well the CAR-T therapy's efficacy holds up over time. On that score, bb2121's progression-free survival mark of 11.8 months comes in roughly at analyst expectations, albeit toward the lower end.
"Updates from [Bluebird's] bb2121 program are critical to readthrough into the ongoing pivotal [Phase 2] KarMMa trial in multiple myeloma and specifically durability in the first cohort and response rates in the second cohort will be closely evaluated by investors," wrote Jefferies analyst Biren Amin in a note to investors prior to ASCO.
Among the aforementioned 22 patients, 50% were in a complete response as of the March 29, 2018 cut-off for the data presented at ASCO. That figure was lower, at 42.9%, for the 14 patients who received a dose of 150 million CAR-T cells, the lowest dose advanced into the Phase 1 study's dose expansion phase.
All 16 patients evaluable for minimal residual disease tested negative, experiencing an even longer median progression-free survival of 17.7 months.
The complete response rates are a slight step-down from Bluebird bio's previous update in December with data from fewer patients, and bb2121 doesn't appear a cure. On a call Friday evening, a main topic of discussion for analysts was whether patients would need to be re-treated, and how the company would address that going forward.
Yet, for an extremely sick group of patients, the response rates are an encouraging sign of bb2121's efficacy. Participants in the expansion phase of the study had their cancer progress from a median of 8 prior treatments, and most previously received autologous stem cell transplants.
As always with CAR-T, safety is a key concern. Overall, treatment with bb2121 appeared largely manageable, with only two patients experiencing Grade 3 or higher CRS. There were no fatal cases of CRS or neurotoxicity. Two patients did die, one from cardiac arrest and another from myelodysplastic syndrome following discontinuation of treatment with bb2121.
For Celgene, which reached a deal in March to split costs and profits on bb2121 with Bluebird in the U.S., the CAR-T treatment is a key pipeline asset. Clinical setbacks elsewhere and pared-back sales forecasts have shaken confidence in the big biotech. And given Celgene's $9 billion acquisition of CAR-T developer Juno Therapeutics earlier this year, cell therapy looks to be a large part of the company's growth story moving forward.
Encouraged by what they're seeing, Bluebird and Celgene are planning a Phase 3 study of the drug in the earlier, third-line setting.
"This is perhaps one of, if not almost the most, important program for [Celgene] other than ozanimod, both of which have multi-billion dollar potential," wrote Jefferies analyst Michael Yee in a June 1 note to investors.
Investors, perhaps hoping for a more robust PFS number, appeared mildly disappointed, sending shares in Bluebird down by 6% in post-market trading Friday.
Bluebird's therapy is still a ways away from reaching regulators' desks. But its positive results should help build confidence that CAR-T therapy could prove clinically useful outside of leukemia and lymphoma, where Novartis and Gilead have won approvals.