The FDA has placed a clinical hold on Hemogenyx Pharmaceuticals’ investigational HEMO-CAR-T, which is being trialed for the treatment of acute myeloid leukemia (AML), the UK-based biotech announced Monday.

In its full review letter, the FDA pointed to manufacturing problems as the reason for the regulatory pause. In particular, the regulator flagged a “splicing deficiency” that arises during the production of the lentivirus that is used to create the CAR-T cells for Hemogenyx’s candidate, according to the company’s press release.

Hemogenyx has already found the source of the splicing issue and has come up with a method to solve it. CEO Vladislav Sandler said in a statement that the company is “confident” that it will “be able to address the FDA’s questions and concerns” regarding HEMO-CAR-T’s Investigational New Drug (IND) application.

The company submitted its IND seeking to launch a Phase I trial for HEMO-CAR-T in May 2023.

In its letter to Hemogenyx, the FDA also outlined suggestions that the biotech can take to further boost the safety profile of HEMO-CAR-T. However, these recommendations do not contribute to the current clinical hold “and can be dealt with readily,” according to the company.

Like other CAR-T-based therapies, HEMO-CAR-T works by first isolating a patient’s T cells and modifying them using a gene construct to allow them to recognize certain proteins expressed on cancer cells. Once these modified T cells have multiplied, they are put back into the patient, where they can seek out and destroy cancer cells.

HEMO-CAR-T sets itself apart from other molecules in the same class by using Hemogenyx’s proprietary humanized monoclonal antibody, which has been designed to target a unique antigen on AML cells, according to the company’s website.

With Monday’s clinical hold, Hemogenyx joins a growing list of biotech companies that have encountered regulatory roadblocks in AML.

In January 2023, Magenta Therapeutics was forced to put a Phase I/II dose-escalation study on hold after a patient died following treatment with its candidate MGTA-117. At a dose of 0.08 mg/kg, the patient in question experienced a grade 5 serious adverse event—respiratory failure and cardiac arrest resulting in death—which was deemed related to the study treatment.

Foghorn Therapeutics encountered a similar problem in August 2022, when a mortality pushed the FDA to put its investigational BRG1/BRM inhibitor, FHD-286, on full clinical hold. The patient’s potential cause of death was differentiation syndrome, which is a serious adverse event often associated with AML treatments. Foghorn's hold was lifted last month.

Other companies that have received regulatory pauses in AML include Curis and Kura Oncology. The Kura hold was lifted in January 2022 while the Curis hold was removed last week.

Source: biospace.com