- Bluebird bio Inc. marked progress on three fronts over the weekend, unveiling encouraging clinical updates on its Lentiglobin gene therapy in beta-thalassemia and sickle cell disease as well as for its CAR-T candidate bb2121 in multiple myeloma.
- New data on bb2121, in particular, showed active doses of the CAR-T therapy delivered a particularly impressive 56% complete response rate in 18 patients — up from 27% at the last update in May, which suggests a deepening response to treatment over time.
- While the number of patients is small, bb2121's emerging profile positions bluebird as a leader in a second wave of CAR-T candidates aimed at a protein called B-cell maturation antigen (BCMA) rather than the CD19 antigen targeted by Gilead Sciences Inc.'s Yescarta and Novartis AG's Kymriah.
Correction: A previous version of this article stated that the patient death in the clinical trial of bb2121 was due to tumor lysis syndrome.
Bluebird bio's study of bb2121, a Phase 1 trial, is aimed at finding an appropriate dose rather than test the cell therapy's effectiveness in relapsed/refractory multiple myeloma.
Even so, the data presented to date are undeniably impressive. Seventeen of 18 patients infused with an active dose of the anti-BCMA CAR-T experienced a response and 10 achieved a complete response (9 of which were negative for minimum residual disease).
This is all the more encouraging given the high number of previous treatments received by patients in the study. Participants had a median of seven prior lines of therapy and 29% were penta-refractory — meaning resistant to five drugs for multiple myeloma, including Johnson & Johnson's Darzalex (daratumumab).
"CAR T-cell therapy is completely different from other available treatments for multiple myeloma," said James Kochenderfer, lead study author and physician at the Center for Cancer Research at the National Cancer Institute, in a statement. "We have patients who have a sustained response and have been able to go for over a year with no additional myeloma therapy and tolerable adverse effects."
Like all CAR-Ts, treatment with bb2121 came with a high number of side effects. Fifteen patients experienced cytokine release syndrome (CRS), a common risk to CAR-T, although only two cases were Grade 3 or higher. Neurotoxicity occurred in five patients, and one case of delayed onset, reversible neurotoxicity accompanied by tumor lysis syndrome and CRS was reported.
Two patients administered active doses died, one from cardiac arrest and another from myelodysplastic syndrome following discontinuation of treatment with bb2121.
Celgene Corp., bluebird's partner on bb2121, has begun recruiting patients into a pivotal Phase 2 study called KarMMa, with a target enrollment of just over 90 patients. Already, some analysts see bb2121 as a growth catalyst for Celgene, which has commercial rights.
Given the excitement around CAR-T at ASH, bluebird would be making headlines even with just bb2121 news. Yet, the biotech also delivered signs of progress from its LentiGlobin gene therapy in two blood disorders: beta-thalassemia and sickle cell disease (SCD).
In a Phase 1 study, two patients treated under a improved manufacturing process showed increased anti-sickling hemoglobin production.
"Data from LentiGlobin in sickle cell disease gives us confidence the [manufacturing] improvements could lead to increased efficacy, and we think a second SCD [patient] has achieved a functional cure," Jefferies analyst Biren Amin wrote in a Dec. 11 note.
And in Northstar-2, a study of Lentiglobin in beta-thalassemia, three patients with more than six months of follow-up were free of the chronic blood transfusions typically needed in individuals with the disorder. Two of those three have hemoglobin levels approaching normal.
While these updates are in only a small handful of patients, it signals that the changes bluebird made to its manufacturing process for LentiGlobin could deliver the hoped-for improvements in efficacy.
Investors certainly agreed, as shares in bluebird jumped by more than 20% Monday morning to crest $220 per share — an all-time high — before paring back some of those gains.