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An Autolus Therapeutics cell therapy has won FDA approval for treating an aggressive blood cancer. It’s the biotech’s first approved product and just the second CAR T-treatment for this particular malignancy. But compared to that other cell therapy and other treatments available, Autolus’s therapy has features that could set it apart from the field. The Autolus therapy, known in development as obecabtagene autoleucel, or obe-cel, is approved to treat adults with advanced cases of B-cell precursor acute lymphoblastic leukemia (ALL). The Friday approval came ahead of the Nov. 16 target date for an FDA decision. London-based Autolus will market its new therapy under the name Aucatzyl. In B-cell ALL, the bone marrow produces too many abnormal B-lymphocytes, a type of white blood cell. Aucatzyl is a CAR T-cell therapy made by harvesting a patient’s T cells and engineering them to go after CD19, a protein abundant on the surfaces of those abnormal cells. It’s the same target addressed by Gilead Sciences’ Tecartus, which received FDA approval for ALL in 2021. But Aucatzyl is engineered to offer better safety and efficacy. presented by Sponsored Post The Promise of Value-Based Care and MedTech Innovation Monica Vajani, Executive Director for mHUB’s MedTech Accelerator, discusses how mHUB is helping innovators transition healthcare towards value-based care. By Monica Vajani - mHUB After recognizing and binding to CD19, Aucatzyl injects its cytotoxic proteins and then disengages from the cancer cell to move on to another cancer cell, a process called “serial killing.” To be fair, other CAR T-therapies, including Tecartus, offer serial killing capability. But Aucatzyl is designed to disengage from each target cell more rapidly than other cell therapies do. This fast “off-rate” is intended to minimize excessive activation of T cells, which in turn could reduce adverse effects to patients. This property could also reduce exhaustion of these engineered cells, thereby improving the therapy’s durability. The FDA’s decision for Aucatzyl is based on the results of an open-label, single-arm trial that enrolled adults with CD19-positive B-cell ALL that had relapsed or had not responded to at least two earlier lines of treatment. The main goal was to measure the rate and duration of complete remission. Of the 65 patients who could be evaluated for efficacy, 27 (42%) achieved complete remission within three months. The median duration of that response was 14.1 months. Aucatzyl’s label carries a black box warning for an excessive immune response called cytokine release syndrome. The warning also flags risks of neurotoxicity and T cell malignancies. Those risks are consistent with the class of CAR T-therapies, which also carry black box warnings. But the rates of severe complications for the Autolus therapy were low. While cytokine release syndrome was reported in 75% of patients, this complication was classified at Grade 3 in just 3% of patients and there were no Grade 4 or 5 events. Neurotoxicity was reported in 64% of participants; this complication was Grade 3 or higher in just 12% of cases. In a note sent to investors, William Blair analyst Matt Phipps said the response rates for Aucatzyl are similar to those of Tecartus. Where Autolus’s drug differentiate itself is with better safety. Phipps notes that Aucatzyl’s rates of complications are lower. He added that unlike other CAR T-therapies, the FDA is not requiring the Autolus product to have a risk evaluation mitigation strategy (REMS), a program that monitors and mitigates the risks of a treatment. Sponsored Post The Future of Hospitals and Pharma Companies Will Depend on Strength of Healthcare Analytics Insights PurpleLab® stands out from others in this sector by providing its data analytics services to several different groups of users across healthcare and pharma companies. By Stephanie Baum “We continue to believe the more tolerable safety profile of Aucatzyl will make it the preferred treatment option for patients with adult ALL and support majority market share over time,” Phipps said. “Interestingly, Aucatzyl is the first CAR T-therapy to be approved without a REMS requirement, which should reduce burden for the treating centers and further support adoption.” Aucatzyl’s safety edge could also support expanding the product’s uses to certain autoimmune disorders driven by excessive B-cell activity. Earlier this year, Autolus began an open-label Phase 1 study evaluating Aucatzyl in systemic lupus erythematosus. Autolus has said that depending on the outcome of this test, it could proceed to further studies in lupus and lupus nephritis among other autoimmune disorders. In the nearer term, Autolus is focusing on commercialization of Aucatzyl in ALL. An Autolus manufacturing facility in Stevenage, United Kingdom, will produce the therapy for global markets. The therapy is still under regulatory review in Europe. Cardinal Health is the distribution partner for the product in the U.S. Aucatzyl enters an ALL market dominated by Amgen’s Blincyto, a CD19-targeting monoclonal antibody. Amgen reported $861 million in 2023 sales for the product, a 48% year-over-year increase. But this drug’s label carries a black box warning for cytokine release syndrome and neurotoxicity. It also offers limited durability. Meanwhile, Tecartus is not a big revenue generator for Gilead, but sales are growing. For 2023, the company reported $370 million in global Tecartus sales, a nearly 23.7% increase compared to the same period in in the prior year. William Blair projects Aucatzyl could achieve about $300 million in peak sales, based on an estimated initial price of $450,000, which would be a slight discount to Tecartus’s $462,000 list price in adult ALL. Autolus will discuss the approval during a conference call scheduled for Monday, 8:30 am Eastern time. Image: Getty Images