BTK

The unique chronic lymphocytic leukemia label gives Breyanzi one leg up against Gilead’s CD19 CAR-T leader, Yescarta. Just as BeiGene’s Brukinsa encroaches on CAR-T territory, Bristol Myers Squibb has brought its CAR-T therapy Breyanzi into a type of blood cancer that’s considered the BTK inhibitor class’s home turf. Breyanzi on Thursday won an FDA accelerated approval for previously treated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), BMS said. To be eligible for the CD19-targeted CAR-T med, a patient must have tried a BTK drug such as Brukinsa and a BCL2 inhibitor such as AbbVie and Roche’s Venclexta. Breyanzi is the first CAR-T cell therapy to enter the CLL/SLL field, where BTK inhibitors are standard first-line treatments. When the FDA accepted BMS’ application in November, there was no standard treatment for CLL/SLL patients who have failed on BTK and BCL2 inhibitors. But the situation has since changed, leaving Breyanzi with at least one competitor in the late-line setting. In December, the FDA cleared Eli Lilly’s oral non-covalent BTK inhibitor Jaypirca in the same post-BTK and -BCL-2 CLL/SLL setting. In the single-arm BRUIN trial, Jaypirca shrank tumors in 72% of patients previously treated with both a BTK and a BCL-2 inhibitor, with the duration of response lasting for a median of 12.2 months. All the responses recorded were partial responses. By comparison, Breyanzi in its own trial demonstrated an overall response rate of 45% among 65 patients who received the CAR-T therapy, according to its updated label. Although the number appears smaller than Jaypirca’s by cross-trial comparison, Breyanzi’s responses included 20% complete responses. In addition, the one-time CAR-T therapy’s median duration of response was also much longer, reaching 35.3 months. “If we look at it, the response rate, the complete response rate and most importantly, the durability of those responses, it’s truly a paradigm shift,” BMS’ chief medical officer, Samit Hirawat, M.D., said of Breyanzi’s data in an interview with Fierce Pharma. Hirawat believes Breyanzi’s single infusion, its durable anti-tumor effect and an established safety profile makes it a solid option in third-line CLL/SLL. But he also acknowledged that Breyanzi, like all other CAR-T therapies, is only administered at designated treatment centers, and therefore its accessibility should be factored into treatment decision-making. Beyond that, “the objective from a patient perspective and a physician perspective is always to give the best therapy as soon as possible and have the best outcome for a patient without having to have a chronically delivered medicine,” Hirawat said. As is the case with Jarypirca, Breyanzi was greenlit with an accelerated approval. BMS has agreed with the FDA to run a separate study in the same third-line setting to confirm Breyanzi’s clinical benefits. The open-label trial will have more patients with a longer-term follow-up of about 15 months post-response, according to Hirawat.  Breyanzi’s sales have been on the uptick, reaching $303 million last year, thanks to a 2022 approval in second-line large B-cell lymphoma. But it still lags behind Gilead Sciences’ CD19 rival, Yescarta, which collected $1.5 billion in 2023 sales. BMS is also awaiting two FDA decisions for Breyanzi in follicular lymphoma and mantle cell lymphoma. The unique CLL/SLL label now gives Breyanzi one leg up against Gilead’s CD19 CAR-T leader. Many cell therapy developers, including BMS, have lately developed an interest in autoimmune diseases. BMS has incorporated Breyanzi’s construct into an autoimmune candidate dubbed CD19 NEX T. Initial phase 1 data for the drug in systemic lupus erythematosus are expected this year. “We’re looking forward to changing [these patients’] life from a quality-of-life perspective, as well as how those comorbidities can be reversed and be impacted,” Hirawat said. He argued that Breyanzi’s safety profile, if replicated in CD19 NEX T, would be acceptable, given its generally low-grade cytokine release syndrome events and neurological toxicities.

Bristol Myers Squibb’s Breyanzi (lisocabtagene maraleucel) became the first CAR-T therapy approved for use in patients with relapsed or refractory chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) following a nod from the FDA. The CD19-directed therapy was first authorised in the US in 2022 for the treatment of certain adults with large B-cell lymphoma.Bryan Campbell, head of commercial, cell therapy at Bristol Myers Squibb, noted that “for years, attempts to bring other CAR-T cell therapies to patients with relapsed or refractory CLL or SLL met challenges and found little success.” The latest accelerated approval is based on response rate and duration of response data from the Phase I/II TRANSCEND CLL 004 study.Results released last year showed that Breyanzi was associated with a complete response (CR) rate of 20%, while the median duration of response was 35.3 months. Meanwhile, high rates of minimal residual disease (MRD) negative status were observed across patients treated with Breyanzi who achieved a CR, with an MRD-negativity rate of 100% in the blood and 92.3% in the bone marrow.Breyanzi’s new indication is for the treatment of adults with relapsed or refractory CLL or small lymphocytic lymphoma SLL who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.More to come.

Dive Brief:For the first time, the Food and Drug Administration has approved a cell therapy for hard-to-treat forms of two blood cancers.Sold as Breyanzi, the therapy is now cleared for use in certain adults with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma who have received at least two prior lines of therapy. There is no established standard of care for such patients, so the FDAs decision to grant an accelerated approval provides a much-needed and potentially transformative option, according to Breyanzis developer, Bristol Myers Squibb.The FDA based its decision on results from a clinical trial that evaluated just shy of 120 participants. The trial found that at a certain dose level, around one in five people given Breyanzi had their cancer completely disappear. In total, 45% of participants responded to the therapy, and those responses lasted a median of just under three years.Dive Insight:Chronic lymphocytic leukemia and small lymphocytic lymphoma are typically slower progressing and more survivable than other cancers. In fact, treatment often isnt necessary in the early stages of the disease. Estimates hold that around 85% of people will live at least five years following a diagnosis.Yet, as these cancers progress, they may require some form of drug intervention. Usually that involves a combination of chemotherapy and targeted medicines like BTK inhibitors, a class of drugs that includes AstraZenecas Calquence and AbbVie and Johnson & Johnsons Imbruvica.For patients who dont respond or stop responding to those treatments, there are few options and poor outcomes, according to Bristol Myers. But the company believes so-called CAR-T cell therapies like Breyanzi can help solve this problem.Breyanzi is made with a patients own white blood cells, which are extracted and then shipped to a manufacturing site. There, they are engineered to better target and destroy malignant B cells that express a protein known as CD-19. The souped up blood cells are then sent back to a treatment center where they get reinfused into the patient.So far, the FDA has approved half a dozen CAR-T therapies, mostly for other blood cancers like follicular lymphoma, multiple myeloma and diffuse large B cell lymphoma. Breyanzi is now the only one indicated for chronic lymphocytic leukemia and small lymphocytic lymphoma.For years, attempts to bring other CAR-T cell therapies to patients with relapsed or refractory CLL or SLL met challenges and found little success, said Bryan Campbell, the commercial head of Bristol Myers cell therapy business, in a statement. But following Thursdays approval, we are now able to offer these patients a personalized option, while further expanding access across the broadest array of B-cell malignancies, to address this critical unmet need.Breyanzi is cleared specifically for people who previously received a BTK blocker and a B-cell lymphoma 2 inhibitor such as AbbVie and Roches Venclexta.The FDA, in granting accelerated approval, noted that Breyanzis benefits in these cancers may need to be verified through one or more additional confirmatory studies.The agency first approved Breyanzi in 2021 as a treatment for adults with relapsed or refractory DLBCL. The drug carries a safety warning for T cell malignancies, neurological side effects, and a kind of immune system reaction called cytokine release syndrome.Editors note: this story has been updated to clarify the date on which the approval decision was issued. '