On March 26, the US Food and Drug Administration (FDA) approved Abecma [idecabtagene vicleucel; ide-cel] as the first B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy for patients with relapsed or refractory multiple myeloma.
The therapy is being jointly developed and commercialized in the US as part of a co-development, co-promotion, and profit share deal between Bristol Myers Squibb (BMS) and bluebird bio.
As an anti-BCMA CAR T cell therapy, Abecma works by recognizing and binding to BCMA, a protein that is nearly universally expressed on cancer cells in multiple myeloma, leading to the death of BCMA-expressing cell, according to the partners.
The FDA’s approval was based on the data from the Phase II KarMMa trial of 127 patients with relapsed or refractory multiple myeloma who had received at least three prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.
A bluebird bio spokesperson told us achieving this regulatory milestone establishes a strong foundation for its broader oncology pipeline and solidifies its commitment to continued innovation on behalf of patients with multiple myeloma. “In multiple myeloma, bluebird bio looks to support the commercial success of Abecma and continue development of our investigational bb21217 product candidate, advancing into earlier lines of treatment and continuing to innovate for the next generation of treatment for these patients.”
Despite advances in treatment, multiple myeloma remains an incurable disease characterized by periods of remission and relapse. Most patients experience relapse following initial therapies, and depth and duration of response as well as survival outcomes decrease with each successive treatment. Patients with relapsed or refractory multiple myeloma that have been exposed to all three major drug classes (triple-class exposed), including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, tend to demonstrate poor clinical outcomes with very low response rates (20% to 30%), short duration of response (2 to 4 months) and poor survival.
There is compelling body of scientific evidence behind Abecma, said bluebird bio. In the pivotal KarMMa trial, the company said the results showed rapid, deep, and durable responses among the majority of patients. The safety profile of Abecma is well-established, it added.
Costs, manufacturing, treatment
Bluebird bio and BMS have set the wholesale list price for the treatment at US$419,500. Asked about projected sales for the next decade, the spokesperson would not be drawn. “As a matter of corporate policy, we are not able to comment on market potential or anticipated sales.”
Abecma will be manufactured for each individual patient using the patient’s own T cells at the BMS cellular immunotherapy manufacturing facility in New Jersey. The lentiviral vector, which is used to engineer the CAR T cells, was developed by bluebird bio.
Is there a way to make this a more affordable treatment with quick manufacturing turnaround times?
“Abecma is a first-in-class anti-BCMA CAR T cell therapy that offers patients with triple-class exposed multiple myeloma a one-time infusion treatment option that delivers rapid, deep and durable responses, representing a significant advancement in treatment for these patients.
“Cell and gene therapies are a new modality and we are pioneering this field as the first CAR T cell therapy for multiple myeloma. We are continuously working to reduce turnaround time via optimization of manufacturing and testing with a goal to make cell and gene therapies more easily available for patients,” said the bluebird representative.
She said the companies are actively working to onboard a network of certified treatment centers to begin treating patients with Abecma in the US. “We anticipate that physicians will be able to begin the treatment experiences within a matter of weeks.”
The Centers for Medicare and Medicaid Services (CMS) in the US have recently established a new CAR T specific reimbursement rate, based on the Diagnosis Related Group (DRG), which is a step forward in recognizing the uniqueness of CAR T treatment, said the spokesperson. “We look forward to continuing to work with the CMS to ensure Medicare patients have access to treatment.”
BMS picked up the partnership deal with bluebird bio as a result of its acquisition of Celgene in 2019.
In May 2020, the partners announced that they had revised terms of the deal whereby bluebird bio would receive US$200m (€183m) in return for the forfeiture of future ex-US milestone payments and royalties.
Bluebird bio said then that the new arrangements would allow it to ‘refocus’ resources on its internal programs and pipeline.
BMS has now sole responsibility for commercialization and manufacturing of ide-cel ex-US.