CD19

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.

SAN DIEGO, March 15, 2024 (GLOBE NEWSWIRE) -- Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, today announced it will participate in a virtual fireside chat on the Treatment Landscape & New Treatment Options for Prostate Cancer. Oncternal’s President and CEO, James Breitmeyer, M.D., Ph.D. will join Oppenheimer Senior Research Biotech Analyst, Hartaj Singh and a prostate cancer Key Opinion Leader on Tuesday, March 19th, 2024 at 11:00 AM ET. Dr. Breitmeyer will discuss the development of Oncternal’s novel dual-acting androgen receptor inhibitor, ONCT-534, the ongoing Phase 1/2 clinical trial ONCT-534-101, and the potential positioning of ONCT-534 within the treatment paradigm of advanced prostate cancer. To join this call, please contact your Oppenheimer institutional salesperson. A replay of the event will be available online at investor.oncternal.com and it will be archived there for at least 30 days. About Oncternal TherapeuticsOncternal Therapeutics is a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies for the treatment of patients with cancers that have critical unmet medical need. Oncternal pursues drug development targeting promising, yet untapped biological pathways implicated in cancer generation or progression, focusing on hematological malignancies and prostate cancer. ONCT-534 is an investigational dual-action androgen receptor inhibitor (DAARI) with demonstrated preclinical activity in prostate cancer models against both unmutated androgen receptor (AR), and against multiple forms of AR aberration. It is a potential treatment for patients with mCRPC with unmet medical need because of resistance to androgen receptor pathway inhibitors, including those with AR amplification, mutations in the AR ligand binding domain (LBD), or splice variants with loss of the AR LBD. Study ONCT-534-101 (NCT05917470) has dosed patients and continues to enroll patients for treatment with mCRPC. ONCT-808 is an investigational autologous chimeric antigen receptor T (CAR T) cell therapy that targets Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1) using the binding domain from zilovertamab. ONCT-808 has demonstrated activity in preclinical models against multiple hematological malignancies and solid tumors and has been shown to be specific for cancer cells expressing ROR1. Oncternal has developed a robust and reproducible manufacturing process that has the potential to reduce the time patients must wait for their individual CAR T therapy to be produced, compared with currently approved CAR T products. Oncternal has dosed patients under Study ONCT-808-101 (NCT05588440) with relapsed or refractory aggressive B-cell lymphoma, including patients who have failed previous CD19 CAR T treatment. Zilovertamab is an investigational monoclonal antibody designed to inhibit the function of ROR1. Zilovertamab has been evaluated in a Phase 1/2 Study CIRM-0001 (NCT03088878) in combination with ibrutinib for the treatment of patients with mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) and marginal zone lymphoma (MZL), which resulted in 100% progression free survival (PFS) at 42 months in CLL patients expressing a p53 mutation/del(17p), a population underserved by current treatment options. Zilovertamab is also being evaluated in an investigator-initiated Phase 1b study of zilovertamab in combination with docetaxel in patients with metastatic castration-resistant prostate cancer (NCT05156905). More information on our company and programs is available at https://oncternal.com/. Contact Information: InvestorsRichard Vincent 858-434-1113rvincent@oncternal.com MediaCorey Davis, Ph.D. LifeSci Advisors 212-915-2577 cdavis@lifesciadvisors.com

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.