A Bristol Myers Squibb cancer immunotherapy that the pharmaceutical giant obtained via its Celgene acquisition was awarded FDA approval Friday, adding one more of this type of personalized medicine as a treatment option for certain forms of lymphoma.
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The FDA approved the therapy, lisocabtagene maraleucel, as a treatment for adults who have certain types of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL), whose cancer has not responded to or has relapsed after at least two other types of treatment. New York-based BMS will market the drug under the name Breyanzi.
The BMS treatment is what’s called a chimeric antigen receptor T cell therapy, or CAR-T. It’s made by taking T cells from a patient and engineering them by inserting a gene that helps the cell target CD19, a protein on the surface of cancer cells. These engineered T cells are multiplied in a lab then infused into a patient.
Two other CAR -T therapies for DLBCL are already on the market: Kymriah, from Novartis, and Yescarta, a Gilead Sciences treatment that was initially developed by Kite Pharma, which was acquired by Gilead. Both treatments were approved in 2017. Gilead has since won a second CAR-T approval. Last summer, the FDA approved Tecartus as a treatment for mantle cell lymphoma.
Liso-cel, the shorthand used to refer to the BMS therapy for most of its history, was initially developed by Juno Therapeutics. Celgene acquired Juno for $9 billion, a 2018 deal that was followed a year later by BMS’s $74 billion acquisition of Celgene. Liso-cel figured prominently in the transaction, singled out as one of three upcoming drug approval decisions that justified the deal. Celgene shareholders stood to gain additional payment, a so-called contingent value right (CVR), if all three drugs were approved by certain dates. Under BMS’s agreement with Celgene, liso-cel needed to be approved by the end of 2020.
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BMS had hoped that liso-cell, which was granted FDA priority review, would receive a regulatory decision by last August. But Covid-19 threw a wrench into those plans by making it difficult for the FDA to conduct the necessary inspection of manufacturing facilities—a problem that has affected other drug companies as well. The inspection eventually took place and BMS and its contract manufacturer responded to the FDA’s questions. But the review process was not completed in time to meet the terms of the CVR agreement.
The FDA approval of Breyanzi was based on the results of a clinical trial that enrolled more than 250 adults whose large B-cell lymphoma did not respond to treatment or had relapsed. The FDA said that the complete response rate to the BMS treatment was 54%.
Like the other CAR-T therapies, Breyanzi does bring the risk of life-threatening side effects. The therapy’s label includes a boxed warning stating that treatment may result in cytokine release syndrome, a systemic immune response to the treatment. The label also warns that the therapy can lead to neurological problems. The labels for both the Novartis and Gilead CAR-T therapies carry similar warnings. Other side effects observed in the Breyanzi clinical trials include infections, low blood cell counts, and a weakened immune system.
The FDA is requiring that BMS develop a plan to inform clinicians and patients about the risks of the therapy, and to mitigate those risks. Among the requirements is a special certification for healthcare facilities that dispense the treatment. Also, all staff involved in prescribing, dispensing, or administering Breyanzi must be trained and certified to recognize and manage the toxic effects of CAR-T treatment. As a condition of the approval, BMS is required to conduct a post-marketing observational study evaluating patients treated with Breyanzi.
As a drug made from a patient’s immune cells, Breyanzi is clearly a cell therapy. The FDA also regards it as a gene therapy because its production involves the introduction of a gene. Breyanzi can now also claim another distinction: It’s a regenerative medicine.
The FDA had previously granted regenerative medicine advanced therapy (RMAT) designation to Breyanzi. This new designation was created under the 21st Century Cures Act, which was signed into law late 2016. The RMAT provision of the act was intended to encourage development of regenerative medicine therapies addressing serious conditions. Friday’s regulatory nod makes Breyanzi the first therapy to win approval under the RMAT designation.
Photo by Flickr user Bristol-Myers Squibb via a Creative Commons license
