Autolus Serial Killing Cell Therapy Receives FDA Approval for Blood Cancer

A cell therapy from Autolus Therapeutics has received FDA approval to treat an aggressive blood cancer. It is the biotech company's first approved product and only the second CAR-T treatment for this specific malignancy. But compared to other cell therapies and other available treatments, Autolus' therapy has features that could set it apart from the competition.

Autolus therapy, known in development as Obecabtagene Autoleucel or Obe-Cel, is approved for the treatment of adults with advanced cases of B-cell precursor acute lymphoblastic leukemia (ALL). Friday's approval came ahead of the FDA's target date of Nov. 16 for a 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 that involves harvesting a patient's T cells and manipulating them to fight CD19, a protein that is abundant on the surface of these abnormal cells. It's the same goal addressed by Gilead Sciences' Tecartus, which received FDA approval for ALL in 2021. However, Aucatzyl was developed to provide better safety and effectiveness.

After recognizing and binding to CD19, Aucatzyl injects its cytotoxic proteins and then detaches 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 the potential for serial killing. But Aucatzyl is designed to detach from each target cell more quickly than other cell therapies. This rapid “off rate” is intended to minimize excessive activation of T cells, which in turn could reduce side effects for patients. This property could also reduce the exhaustion of these manipulated cells, thereby improving the durability of the therapy.

The FDA's decision for Aucatzyl was based on the results of an open-label, single-arm study that enrolled adults with CD19-positive B-cell ALL who had relapsed or failed to respond to at least two prior lines of treatment. The main objective was to measure the rate and duration of complete remission. Of the 65 patients whose efficacy was evaluated, 27 (42%) achieved complete remission within three months. The mean duration of this response was 14.1 months.

Aucatzyl's label has a black box warning about an excessive immune response called cytokine release syndrome. The warning also highlights the risk of neurotoxicity and T-cell malignancies. These risks are consistent with the class of CAR-T therapies, which also come with black box warnings. However, rates of severe complications with Autolus therapy were low. While cytokine release syndrome was reported in 75% of patients, this complication was graded as grade 3 in only 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 only 12% of cases.

In a note to investors, William Blair analyst Matt Phipps said response rates for Aucatzyl were similar to Tecartus. The difference between Autolus medications is better safety. Phipps notes that complication rates are lower with Aucatzyl. He added that unlike other CAR-T therapies, the FDA does not require the Autolus product to have a Risk Evaluation Mitigation Strategy (REMS), a program that monitors and mitigates the risks of a treatment.

“We continue to believe that Aucatzyl's more tolerable safety profile will make it the preferred treatment option for patients with adult ALL and secure a majority of market share over time,” Phipps said. “Interestingly, Aucatzyl is the first CAR-T therapy to be approved without a REMS requirement, which should reduce the burden on treatment centers and further encourage adoption.”

Aucatzyl's safety benefit could also support the expansion of the product's uses to certain autoimmune diseases caused by excessive B-cell activity. Earlier this year, Autolus began an open-label Phase 1 study evaluating Aucatzyl in systemic lupus erythematosus. Autolus said that depending on the results of this test, further studies could be conducted on lupus and lupus nephritis, as well as other autoimmune diseases.

In the short term, Autolus is focused on commercializing Aucatzyl in ALL. An Autolus manufacturing facility in Stevenage, UK, will produce the therapy for global markets. The therapy is still undergoing regulatory testing in Europe. Cardinal Health is the distributor for the product in the USA

Aucatzyl enters an ALL market dominated by Amgen's Blincyto, a CD19-targeting monoclonal antibody. Amgen reported 2023 sales of $861 million for the product, up 48% from the previous year. However, there is a black box warning on the label of this drug about cytokine release syndrome and neurotoxicity. It also offers a limited shelf life. Meanwhile, Tecartus isn't a big revenue generator for Gilead, but sales are growing. For 2023, the company reported global Tecartus revenue of $370 million, an increase of nearly 23.7% compared to the same period last year.

William Blair predicts Aucatzyl could achieve peak sales of about $300 million based on an estimated starting price of $450,000, which would be a slight discount to Tecartus' adult ALL list price of $462,000. Autolus will discuss the approval during a conference call scheduled for Monday at 8:30 a.m. Eastern Time.

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