Autolus' CD19 CAR-T posts 100% complete response rate, zero grade 3 CRS in small lymphoma trial

Autolus Therapeutics has linked its CD19 CAR-T to a 100% complete response rate in a small indolent B-cell lymphoma trial. AUTO1 drove the responses without causing any grade 3 or worse cytokine release syndrome (CRS), sending shares in the biotech up 35%.

The results, full details of which Autolus will share at the European Hematology Association Virtual Congress next month, come from nine adults with relapsed or refractory low grade B-cell lymphoma despite high disease burden. All patients went into complete remission. No patients suffered grade 3 CRS, and only one participant had a grade 2 cytokine reaction. There were four cases of grade 1 CRS.

It is still early days for the trial—the median duration of response is 3.1 months—and the sample size is small. The available data offer encouragement, though, with the complete response rate and level of grade 3 CRS improving on the data generated during the development of Yescarta. 

“Initial safety signal seems differentiated, consistent with the observation in adult ALL. We believe 'flexible CD19 binder', which imitates natural T-cell signaling, drives the better safety. AUTO1 is poised for oppy when CART moves to earlier lines of therapy, in our view,” analysts at Jefferies wrote in a note to investors.

Seven of the patients had follicular lymphoma. The other two had mantle cell lymphoma. Eight of the patients are in remission, with the duration of responses ranging from one to 5.6 months. The ninth patient died of COVID-19 after being in remission for 5.6 months. 

The lack of any grade 3 CRS was marred slightly by a case of uncontrolled T-cell and macrophage activation and proliferation in one patient. However, physicians resolved the case using anakinra and dexamethasone.

Investors responded favorably. At below $7, Autolus’ stock is still well down on the $17 price its shares commanded at the time of its 2018 IPO, let alone the $48 it hit during a spike later that year. Yet, the results are still a sign of a stirring of a potential turnaround after a period in which Autolus has been battered by setbacks that led it to reduce its headcount by 20% and trim its pipeline at the start of this year.

The changes increased Autolus’ focus on AUTO1. Whether that decision pays off in the near term will largely rest on a phase 1b/2 clinical trial that is recruiting 185 adults with relapsed or refractory B-cell acute lymphoblastic leukemia and could provide data that support registration. Autolus’ work on other B-cell malignancies is at a more exploratory stage.

Validating AUTO1 in the clinic will answer some of the questions about AUTO1. However, positive data will still leave questions about the commercial potential of AUTO1. Existing CD19 CAR-Ts just had their best quarter yet, but, at $342 million, sales of Novartis’ Kymriah and Gilead’s Yescarta and Tecartus are yet to hit the once-forecasted highs.

If risk-benefit concerns underpin the slow uptake of CD19 CAR-T therapies to date, AUTO1 may have a shot at selling better, but as another autologous therapy the candidate may struggle commercially if price and logistical complexity are the barriers, particularly if allogeneic products come to market.