Autolus Therapeutics’ biologics license application (BLA) for obecabatagene autoleucel (obe-cel) in relapsed/refractory (r/r) adult B-Cell acute lymphoblastic leukemia (ALL) has been accepted for filing by the FDA, with a Prescription Drug User Fee Act (PDUFA) date set for November 16, 2024.1
The agency does not have plans for an advisory committee meeting to discuss obe-cel, which is an investigational autologous CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy. Autolus noted that the PDUFA date is in line with expectations based on review timelines for other CAR-T therapy BLAs. Within the first half of this year, the company also intends to submit a marketing authorization application to the European Medicines Agency for obe-cel in the same indication.
“Acceptance of the BLA filing is an important milestone for Autolus and we look forward to continuing our collaboration with the FDA during the review cycle,” Christian Itin, PhD, the chief executive officer of Autolus, said in a statement.1 “With the PDUFA date set for November, we remain focused on preparing for the potential launch of obe-cel.”
The BLA, which was originally submitted in November 2023, is supported by data from the pivotal phase 1b/2 FELIX clinical trial (NCT04404660).2 Updated data from this clinical trial was presented as part of a pooled analysis with data from the phase 1 ALLCAR19 trial (NCT02935257) at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 9-12, in San Diego, California.3 ALLCAR19 was originally open to patients aged 16 years and older with r/r B-ALL, but later had its eligibility criteria expanded for an extension study that included patients with r/r B-cell chronic lymphocytic leukemia and r/r B-cell nonHodgkin lymphoma.
Key Takeaways
- Autolus Therapeutics’ biologics license application (BLA) for obecabatagene autoleucel (obe-cel) in relapsed/refractory (r/r) adult B-Cell acute lymphoblastic leukemia (ALL) has been accepted for filing by the FDA, with a Prescription Drug User Fee Act (PDUFA) date set for November 16, 2024.
- The agency does not have plans for an advisory committee meeting to discuss obe-cel, which is an investigational autologous CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy.
- Within the first half of this year, the company also intends to submit a marketing authorization application to the European Medicines Agency for obe-cel in the same indication.
Among 20 patients in ALLCAR19 (data cutoff June 2023) and 16 in FELIX (data cutoff March 2023), 29 patients (81%) achieved complete remission (CR) with incomplete hematologic recovery per investigator assessment. The event-free survival rate was 64% at 6 months and 49% at 12 months. Thirteen of 36 responders (36%) remained in remission (8 from ALLCAR19 and 5 from FELIX) with minimal residual disease negativity with a median of 43 months (range, 19-62) of follow up. Two of these ongoing responders had consolidation with allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 10 who did not still had detectable CAR T-cells at the last follow up. The estimated 2-, 3- and 4-year overall survival rates were 44%, 39% and 39%, respectively.
“The combined analysis of data from the ALLCAR19 and FELIX phase 1b studies shows long-term efficacy and safety of obe-cel in patients with r/r B-ALL, with approximately one-third of patients still in remission without consolidative allo-HSCT after a median follow up of >3 years,” Claire Roddie, MD, PhD, FRCPath, MBChB, MRCP, associate professor, haemato-oncology, University College London, who presented the data, and her colleagues wrote.3 “Durable responses of >2 years were also seen in patients with r/r B-CLL and r/r B-NHL. B-cell aplasia was commonly found in long-term follow up of obe-cel recipients, but without a corresponding rise in serious late infections. Obe-cel can effect durable long-term remissions in B-cell malignancies."
Obe-cel incorporates a novel fast off-rate CD19 binding domain intended to shorten the time that CAR T-cells bind to leukemia cells, which could simultaneously decrease the number of cytokines secreted and reduce the rate of T-cell exhaustion.4 At the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois, CGTLive™’s sister publication OncLive™ spoke with Roddie about the potential advantage of this design.
“...We know that other products on the market for adult ALL have got significant toxicity profiles and that's actually really difficult for us physicians to manage and particularly difficult for the patients and their families,” Roddie told OncLive. “It makes it difficult to anticipate or imagine a clinical world where we can give these comfortably as outpatient therapies, which is obviously where [we want to go]—we want to be able to improve the patient experience, quality of life, etc. And so, I think that's where obe-cel comes into this because the toxicity profile is so much less difficult for patients to tolerate—even patients with lots and lots of disease—and I think that's its biggest selling point. From the perspective of just safely navigating patients through this therapy, it’s much more straightforward.”
REFERENCES
1. Autolus Therapeutics announces acceptance of biologics license application for obecabtagene autoleucel (obe-cel) as a potential treatment for relapsed/refractory adult B-cell acute lymphoblastic leukemia (ALL). News release. Autolus Therapeutics plc. January 22, 2024. Accessed January 22, 2024. https://autolus.gcs-web.com/news-releases/news-release-details/autolus-therapeutics-announces-acceptance-biologics-license
2. Autolus Therapeutics submits biologics license application to U.S. Food and Drug Administration for obecabtageneautoleucel (obe-cel) for patients with relapsed/refractory (r/r) adult B-cell acute lymphoblastic leukemia (ALL). News release. November 27, 2023. Accessed January 22, 2024. https://autolus.gcs-web.com/news-releases/news-release-details/autolus-therapeutics-submits-biologics-license-application-us
3. Roddie C, Tholouli E, Shaughnessy P, et al. Long-term efficacy and safety of obecabtageneautoleucel (obe-cel) in adult patients (pts) with relapsed/refractory B-cell acute lymphoblastic leukemia ([R/R B-ALL]; pooled analysis from ALLCAR19 and FELIX phase Ib studies) or other B-cell malignancies (ALLCAR19 extension study). Presented at: 2023 ASH Annual Meeting & Exposition, December 9-12; San Diego, California. Abstract 2114.
4. Roddie C, Sandhu KS, Tholouli E, et al. Safety and efficacy ofobecabtagene autoleucel (obe-cel, AUTO1), a fast-off rate CD19 CAR, in relapsed/refractory adult B-cell acute lymphoblastic leukemia (r/r B-ALL): Top line results of the pivotal FELIX study. Presented at: the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois. Abstract #7000
