Bcl-2

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.

The European Medicines Agency (EMA) released a report detailing the reasons for the withdrawal of Novartis marketing authorisation application for Vijoice. Credit: Bloomberg via Getty Images. The European Medicines Agency (EMA) recently released its main concerns with Novartis ’ Vijoice (alpelisib) application which led to the company withdrawing its conditional authorisation application for a group of rare genetic disorders last autumn. In Europe, Novartis was pursuing a label for the treatment of adults and children aged two years and above with severe or life-threatening symptoms of PIK3CA-Related Overgrowth Spectrum (PROS) requiring systemic therapy. In an updated withdrawal assessment report that was released earlier today (14 March), the EMA explained that the long-term safety profile of Vijoice, especially its impact on growth and development in the paediatric population, is still unknown. Furthermore, it questioned whether the assessment of tumour size was an adequate measure of patient benefit in the group of patients with the target indication. The US Food and Drug Administration (FDA) approved Vijoice in April 2022 as the first and only treatment for select patients with PROS. In May 2019, the regulator also granted approval to alpelisib, under the brand name Piqray . The treatment was made available for postmenopausal women and men with hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-), PIK3CA-mutated advanced or metastatic breast cancer. PROS are a group of genetic disorders in which mutations occur in the PIK3CA gene, causing overgrowth of certain body parts. Vijoice treats the condition by inhibiting the PI3K/Akt signalling pathway. See Also: Novartis exercises option to acquire IFM Due for $835m Novartis files patent for combination therapy for b-cell lymphoma with CD19 car and BCL2 inhibitor In October 2023, Novartis withdrew its EU marketing authorisation application for Vijoice following an EMA evaluation. At the time of withdrawal, the agency reported concerns that the clinical data, provided from the EPIK-P2 study (NCT04589650), was not sufficient in demonstrating the exact effect of the medicine on tumour size and whether patients experienced significant reductions in tumour size. In a letter to the EMA released in the same month, Novartis had also expressed the need to acquire further data to support the drug’s benefit/risk assessment. Novartis submitted the initial application based on real-world evidence from a retrospective chart review study. However, the Swiss company was unable to answer all questions from the Committee for Medicinal Products for Human Use (CHMP) within the necessary timeframe. At the time, the Swiss company announced intentions to submit a new marketing authorisation application once it collects new data. The EMA designated the drug as an orphan medicine on 26 March 2021 for the treatment of PROS. In the EU, there are currently no disease-modifying treatments available for PROS.