Diffuse large B-cell lymphoma (DLBCL) is a type of non-Hodgkin’s lymphoma. There are two anti-CD19 chimeric antigen receptor (CAR)-T cell therapies currently approved for this indication: Gilead’s Yescarta (axicabtagene ciloleucel) and Novartis’ Kymriah (tisagenlecleucel). Autolus Therapeutics is developing AUTO3, a pioneer dual-antigen anti-CD19 / CD22 CAR-T cell product for DLBCL, which promises reduced toxicity and higher efficacy than its competitors. Data presented at the virtual European Society for Medical Oncology (ESMO) 2020 annual conference on 19-21 September from the ALEXANDER Phase I / II study showed that AUTO3 is active in relapsed / refractory (R / R) DLBCL patients.
The upregulation of PD-L1 upon CAR-T treatment may be responsible for T-cell exhaustion and thus reduced efficacy. Autolus Therapeutics is trying to circumvent this issue by using a prophylactic dose of Merck’s Keytruda (pembrolizumab) prior to CAR-T cell infusion. However, due to the Phase I nature of the study, patients have received Keytruda at different time points, standardised for the initiation of Phase II. The data presented at ESMO were from 30 evaluable patients. A total of 170 patients are expected to enrol in Phase I. The overall response rate (ORR) was 68%, and 14 out of 15 patients who achieved a complete response remained in remission for over six months. There was no Grade 3 or higher cytokine release syndrome (CRS) events. Neurotoxicity was also very low, at 5.7% of treated patients experiencing Grade 3 or higher events.
While these data are only from a few patients, they compare very favourably to the competition. The trial is taking place in the outpatient setting, and Autolus Therapeutics believes that AUTO3 can be the only CAR-T agent in the market that does not require hospitalisation and can be used in outpatient facilities. The lack of CRS events and limited neurotoxicity alone could be enough to push AUTO3 ahead of the competition upon confirmed data in a registrational trial, as adverse events have notoriously limited the utilisation of Yescarta and Kymriah.
The date for potential marketing authorisation for AUTO3 is still uncertain. Autolus Therapeutics will make a strategic decision about the Phase II portion of the study soon, which may open the door to using data from ALEXANDER for a future biologics license application. With Yescarta and Kymriah already solidified as options in R / R DLBCL, AUTO3 will have to demonstrate a significant competitive advantage to gain a high patient share. GlobalData forecasts that the DLBCL CAR-T cell market is worth over $500M globally as of 2020. With the possible market entry of an agent that allows for easier administration, the value of this market has the potential to grow. Importantly, the same antigens can also target R / R acute lymphocytic leukaemia, highlighting a market expansion opportunity for Autolus.