Autolus' Cell Therapy for Blood Cancer Wins FDA Approval

Autolus Therapeutics has secured FDA approval for its first product, a cell therapy named Aucatzyl, designated to treat an aggressive form of blood cancer. This marks the biotech's initial foray into the market and presents a significant option for patients with advanced B-cell precursor acute lymphoblastic leukemia (ALL). The approval arrived earlier than the expected November 16 decision date.

Aucatzyl represents a CAR T-cell therapy, which involves modifying a patient’s T cells to target and attack CD19, a protein prevalent on malignant cells in B-cell ALL. This specific therapy differs from Gilead Sciences' Tecartus, another CAR T-cell treatment approved in 2021 for the same condition, by offering enhanced safety and efficacy features.

The development of Aucatzyl’s mechanism allows it to bind to CD19 on cancer cells, inject cytotoxic proteins, and then swiftly detach, enabling it to target subsequent cancer cells in a process known as “serial killing.” While other CAR T-cell therapies also exhibit this capability, Aucatzyl distinguishes itself by its faster disengagement rate. This rapid 'off-rate' is designed to reduce undue T cell activation, potentially mitigating adverse effects and improving the longevity of the engineered cells.

The FDA’s approval of Aucatzyl was based on data from an open-label, single-arm clinical trial involving adults with CD19-positive B-cell ALL, who had either relapsed or did not respond to at least two prior treatments. The study's primary endpoint was to determine the complete remission rate and its duration. Among 65 patients evaluated, 42% achieved complete remission within three months, with a median response duration of 14.1 months.

Aucatzyl’s approval comes with a black box warning for cytokine release syndrome, neurotoxicity, and T cell malignancies. These risks are characteristic of CAR T-therapies, but the incidence of severe complications with Aucatzyl was relatively low. For instance, while cytokine release syndrome was observed in 75% of patients, only 3% experienced it at a severe Grade 3 level, with no Grade 4 or 5 incidents. Neurotoxicity affected 64% of participants, with severe cases (Grade 3 or higher) in just 12% of instances.

William Blair analyst Matt Phipps noted that Aucatzyl’s response rates are comparable to those of Tecartus, but its lower complication rates provide a safety advantage. Unlike other CAR T-therapies, the FDA has not mandated a risk evaluation mitigation strategy (REMS) for Aucatzyl, potentially easing the burden on treatment centers and promoting adoption.

The favorable safety profile of Aucatzyl could support its use beyond ALL, extending to autoimmune diseases characterized by overactive B-cell activity. Autolus has already initiated a Phase 1 study to explore Aucatzyl’s application in treating systemic lupus erythematosus. Depending on these results, further studies could investigate the therapy’s effectiveness in lupus nephritis and other autoimmune conditions.

In the short term, Autolus is concentrating on the commercial launch of Aucatzyl for ALL. The company’s facility in Stevenage, United Kingdom, will handle the global production, and Cardinal Health will distribute the product in the United States. Aucatzyl is currently awaiting regulatory approval in Europe.

Aucatzyl enters a market where Amgen’s Blincyto, a CD19-targeting monoclonal antibody, is a significant player, with 2023 sales reaching $861 million—a 48% increase from the previous year. However, Blincyto's label also includes warnings for cytokine release syndrome and neurotoxicity, and it offers limited durability. While Gilead's Tecartus has not seen substantial revenue, it is showing growth, with 2023 global sales up by nearly 23.7% year-over-year, totaling $370 million.

William Blair forecasts that Aucatzyl could achieve peak sales of around $300 million, with an initial price set at $450,000, slightly less than Tecartus’s $462,000 list price for adult ALL. Autolus plans to discuss this approval further during a conference call scheduled for Monday, 8:30 am Eastern time.