BioPharma, Pharma

bluebird shares recover after slump following ASCO CAR-T data presentation

Progression-free survival rates from bb2121 in multiple myeloma still impress despite investor reaction.

Shares of bluebird bio shrugged off their pre-market losses Monday morning after a Friday afternoon data presentation of its CAR-T therapy for multiple myeloma at the American Society of Clinical Oncology’s annual meeting in Chicago drew concerns about patient relapses.

The Cambridge, Massachusetts-based company’s stock hit a pre-market low of $165.05 per share Monday, but shot up to $196.68 10 minutes after markets opened, before settling down to $186.45 in the early afternoon – still above Friday’s closing price of $182.40. The company is developing the therapy, bb2121, under a partnership with Celgene.

Data from the ASCO meeting showed that 22 patients the Phase I study of bb2121 receiving the highest dose, 150 million cells, showed a median progression-free survival (PFS) – meaning the amount of time patients survive without their disease worsening – of 11.8 months. Patients in the 150 million-cell dose-expansion cohort had received a median of eight prior therapies, with a maximum of 23.

Such a heavily pretreated population typically experiences about 4.4 months of PFS, said Wim Souverijns, who heads global marketing in hematology and oncology for Celgene, in an interview at ASCO. The hit that bluebird’s stock took is because people had the false expectation that the therapy would cure patients, he said, given that CAR-T therapies are seen as curative in other diseases, especially diffuse large B-cell lymphoma. The data from the bb2121 study does not indicate a cure, but it does create a rationale to bring the therapy earlier into treatment, where there is more potential for a cure.

Indeed, the PFS result is not a cure, but it is still very impressive, said Michel Pavic, a professor of medicine and myeloma specialist at the University of Sherbrooke, Quebec, who did not take part in the study.

Still, Pavic said the myeloma community had hoped that the data would indicate a cure. Additionally, he pointed out that even patients who had achieved minimal residual disease (MRD) negativity – meaning less than one myeloma cell per million cells in the bone marrow – still relapsed anyway. As such, it’ll be important to understand why that is the case. However, Souverijns cautioned that myeloma is still a disease that is incurable, and even a single myeloma cell can cause the disease to come back.

All of the 16 patients evaluable for MRD status were judged MRD-negative, according to a next-generation sequencing assay. Median PFS among MRD-negative patients was 17.7 months.

In addition to the Phase I study, bluebird and Celgene are running a registration-directed Phase II study of bb2121 in 94 patients. The CAR-T targets BCMA, a protein on the surface of myeloma cells that is also targeted by other investigational therapies for the disease. These include other drugs Celgene is developing, including a BCMA-targeting bispecific antibody that it acquired when it bought Swiss biotech EngMab for $600 million in 2016, and an antibody-drug conjugate being developed under a partnership with Sutro Biopharma. In addition, its acquisition of CAR-T developer Juno Therapeutics last year gave it control of another BCMA-targeting CAR-T, JCARH125, currently in early development.

In terms of competition, Johnson & Johnson subsidiary Janssen announced plans to kick off a Phase Ib/II trial with a BCMA-targeting CAR-T developed by Nanjing, China-based Legend Biotech. In addition, GlaxoSmithKline is developing an antibody-drug conjugate targeting BCMA, GSK2857916.

Photo: Alaric DeArment, MedCity News