The FDA has lifted its clinical hold on Hemogenyx Pharmaceuticals’ investigational new drug (IND) application for HEMO-CAR-T, an autologous chimeric antigen receptor T-cell (CAR-T) therapy developed with the use of Hemogenyx’s proprietary humanized monoclonal antibody against an acute myeloid leukemia (AML) target.1,2
Hemogenyx noted that the agency confirmed all issues pointed out in the initial clinical hold letter from June 2023 had been sufficiently addressed by the company. Hemogenyx now has a green light to go forward with its plans for a phase 1 clinical trial for HEMO-CAR-T.
“We are extremely pleased with the FDA’s decision to lift the clinical hold,” Vladislav Sandler, PhD, the CEO and cofounder of Hemogenyx, said in a statement.1 “We now look forward to accelerating clinical development of HEMO-CAR-T and to offering patients a potentially life-saving treatment. The removal of the clinical hold was made possible by the hard work and dedication of the entire Hemogenyx Pharmaceuticals team and its Board of Directors and advisors.”
The June 2023 letter identified a splicing that occurs during the manufacturing process of the lentivirus vector as the reason for the hold.3 In July 2023, Hemogenyx announced that it had identified the source of the splicing issue, had developed a method to eliminate it, and was in the process of remanufacturing the lentivirus. The FDA's full review letter regarding the clinical hold also included several suggestions on how to improve the safety of HEMO-CAR-T that were not related to the hold, which the company also stated in the aforementioned July announcement that it was seeking to address. Furthermore, Hemogenyx stated in September 2023 that it had come into alignment with the FDA on a plan to resolve the clinical hold.2 In January 2024, the company sent a complete response letter on the hold to the agency.4 In January the company also noted that all tests across a process qualification run of the end-to-end manufacturing process for HEMO-CAR-T were finished, making up a critical piece of the aforementioned plan to have the hold lifted.5
- The FDA has lifted the clinical hold on Hemogenyx Pharmaceuticals' investigational new drug (IND) application for HEMO-CAR-T, an autologous chimeric antigen receptor T-cell (CAR-T) therapy developed with the use of Hemogenyx’s proprietary humanized monoclonal antibody against an acute myeloid leukemia (AML) target.
- Hemogenyx addressed the issues raised by the FDA in the June 2023 letter, which particularly focused on a splicing issue during the manufacturing process of the lentivirus vector.
- Hemogenyx now has a green light to go forward with its plans for a phase 1 clinical trial for HEMO-CAR-T.
“We are pleased to have filed a complete response to the FDA addressing their concerns that resulted in a clinical hold of the HEMO-CAR-T IND,” Sandler said in a January 2024 statement.4 “We look forward to becoming a clinical stage biopharmaceutical company once consent is received from the FDA.”
Hemogenyx was not the only company to receive an FDA clinical hold in the summer of 2023 for a CAR-T trial in AML. In August 2023, the FDA placed a formal clinical hold on the phase 1 PLAT-08 clinical trial (NCT05105152) evaluating 2seventy bio’s SC-DARIC33, an investigational CD33-directed CAR-T therapy for AML, in relation to the death of the first patient treated at the study’s second dose level (5x106 SC-DARIC33 T-cells/kg).6 2seventy bio has not yet announced a lifting of the clinical hold.
“It cannot be stated enough that the safety of every patient who participates in our studies or receives our therapies is of utmost priority to us and we continue to keep the patient’s family in our thoughts,” Steven Bernstein, MD, the chief medical officer of 2seventy bio, said in an August 2023 conference call and live webcast.7 “...In collaboration with Seattle Children’s, both our partner and the regulatory study sponsor, we have been conducting a thorough investigation of the root cause of this event. This investigation has provided insights into the pathobiology of this toxicity leading to several study protocol changes which the team believes may mitigate this toxicity and allow for the continuation of the PLAT-08 study... We will continue to collaborate with Seattle Children’s and the FDA to determine appropriate next steps and a potential path forward here.”
1. FDA consents to phase I trials of HEMO-CAR-T. News release. Hemogenyx Pharmaceuticals plc. February 9, 2024. Accessed February 12, 2024. https://hemogenyx.com/investors/investors/announcements/announcement/2024/fda-consents-to-phase-i-trials-of-hemo-car-t/
2. Hemogenyx Pharmaceuticals PLC - clinical hold lift plan is accepted by FDA. News release. Hemogenyx Pharmaceuticals. September 14, 2023. Accessed February 12, 2024. https://www.accesswire.com/783926/hemogenyx-pharmaceuticals-plc-clinical-hold-lift-plan-is-accepted-by-fda
3. Hemogenyx Pharmaceuticals PLC Announces Full FDA Review for HEMO-CAR-T IND. News release. Hemogenyx Pharmaceuticals. July 10, 2023. Accessed February 12, 2024. https://www.biospace.com/article/releases/hemogenyx-pharmaceuticals-plc-announces-full-fda-review-for-hemo-car-t-ind/
4. Submission of complete response to clinical hold for HEMO-CAR-T IND. News release. Hemogenyx Pharmaceuticals plc. January 16, 2024. Accessed February 12, 2024. https://hemogenyx.com/investors/investors/announcements/announcement/2024/submission-of-complete-response-to-clinical-hold-for-hemo-car-t-ind/
5. HEMO-CAR-T process qualification run completed. News release. Hemogenyx Pharmaceuticals plc. January 8, 2024. Accessed February 12, 2024. https://hemogenyx.com/investors/investors/announcements/announcement/2024/hemo-car-t-process-qualification-run-completed/
6. 2seventy bio reports second quarter financial results and recent operational progress. News release. 2seventy bio, Inc. August 14, 2023. Accessed February 12, 2024. https://ir.2seventybio.com/news-releases/news-release-details/2seventy-bio-reports-second-quarter-financial-results-and-0
7. 2seventy bio, Inc. 2Q23 earnings conference call. Website. August 14, 2023. 2seventy bio. https://ir.2seventybio.com/events/event-details/2seventy-bio-inc-2q23-earnings-conference-call