FDA Activity Recap: November 2024 Features 3 New Approvals, a BLA Acceptance, and More

Last month, November 2024, the CGTLive^® team was diligently tracking the FDA's activities related to the development of cell and gene therapies for the treatment of rare, complex, and otherwise challenging diseases and disorders.

The agency has continued to ramp up its activities around these therapies as more of them progress through the pipeline in tandem. Last month proved no different, with the FDA approving new products for relapsed or refractory (r/r) B-cell precursor acute lymphoblastic leukemia (ALL), aromatic L-amino acid decarboxylase (AADC) deficiency, and unrelated donor hematopoietic progenitor cell transplantation procedures. Our team has highlighted these, and several other important actions, below.

Click the read more buttons for more details and information about each update.

FDA Approves Obe-Cel for Adults With R/R B-Cell Precursor Acute Lymphoblastic Leukemia

November 8, 2024 — The FDA announced that is has approved obecabtagene autoleucel (Aucatzyl; Autolus Inc), known colloquially as obe-cel, a CD19-directed genetically modified autologous T-cell immunotherapy, for the treatment of adults with r/r B-cell precursor ALL. The therapy was approved based on the findings of the pivotal phase 1b/2 FELIX clinical trial (NCT04404660), which showed rates of overall complete remission (CR) above 60% and a median duration of remission beyond 12 months for those who achieved complete remission within 3 months.

The agency's total recommended dose of obe-cel is 410×10⁶ CD19 chimeric antigen receptor (CAR)-positive viable T-cells, preceded by fludarabine and cyclophosphamide lymphodepleting chemotherapy and administered as split-dose infusion on Day 1 and Day 10 (±2 days) of treatment, based on bone marrow blast assessment. No REMS was required by the FDA.

“Adult ALL is an extremely aggressive cancer, and there is a high unmet medical need that exists in the treatment of patients with this disease once they relapse, where historically they suffer from poor outcomes,” Elias Jabbour, MD, the lead investigator of the US-based portion of the FELIX study and a professor of Leukemia and ALL section chief at The University of Texas MD Anderson Cancer Center, said in a statement. “This milestone approval, based on the demonstrated clinical benefit of Aucatzyl, brings new hope for adult patients with r/r B-ALL.”

FDA Approves PTC Therapeutics’ Gene Therapy Kebilidi for AADC Deficiency

November 13, 2024 — PTC Therapeutics’ eladocagene exuparvovec, a recombinant adeno-associated virus serotype 2 (AAV2)-based gene therapy, has been approved by the FDA for the treatment of children and adults with AADC deficiency. Notably, the indication covers the full spectrum of disease severity and the approval constitutes the first gene therapy for direct administration to the brain to be approved in the United States. The product will be marketed in the US under the name Kebilidi; in the European Union and United Kingdom, it is marketed as Upstaza.

Kebilidi is delivered to the putamen via a 1-time treatment with a stereotactic surgical procedure and provides a functional copy of DDC, the disease-targeted gene. The FDA's approval was made based on data from the global phase 1/2 PTC-AADC-GT-002 clinical trial (NCT04903288). The decision was made under an accelerated approval pathway and PTC noted that long-term follow-up data from patients treated in the study will be provided as confirmatory evidence at a later date. The FDA cited change from baseline in gross motor milestone achievement at 48 weeks posttreatment as an efficacy finding supporting the approval.

"PTC has once again pioneered a new approach to treating highly morbid neurologic diseases," Matthew B. Klein, MD, the chief executive officer of PTC Therapeutics, said in a statement. "I am proud of our team's unwavering commitment to achieve this important regulatory milestone. We look forward to bringing this transformational gene therapy to children and adults with AADC deficiency in the United States."

FDA Approves StemCyte’s Cord Blood Cell Therapy Regenecyte for Unrelated Donor Hematopoietic Progenitor Cell Transplantation Procedures

November 26, 2024 — The FDA has approved StemCyte’s Regenecyte, an allogeneic hematopoietic stem cell therapy derived from human umbilical cord blood, for use in unrelated donor hematopoietic progenitor cell transplantation procedures alongside an appropriate preparative regimen for hematopoietic and immunologic reconstitution in patients with inherited or acquired disorders affecting the hematopoietic system, including those resulting from myeloablative treatment.

"With one of the largest inventories of cord blood stem cells worldwide, StemCyte is uniquely positioned to supply, manufacture, and develop advanced cell therapy products," Tong Young Lee, PhD, the chief executive officer of StemCyte, said in a statement. "Looking ahead, we are committed to driving the development of innovative therapies, achieving sustainable growth through diversified business strategies, and solidifying our position as a global leader in the field of cell therapy."

The FDA’s decision was based on data from the COBLT clinical trial (Study 1), a retrospective review of data from literature and observational studies (Study 2), and data from the Center for International Blood and Marrow Transplant Research (Study 3). Among 324 patients treated in Study 1, 76% achieved neutrophil recovery at 42 days posttreatment (Day 42) (71%, 81%)(ANC >500/µL) (95% CI), 57% achieved platelet recovery at Day 100 (51%, 63%) (20,000/uL) (95% CI), and 65% achieved erythrocyte recovery at Day 100 (58%, 71%) (95% CI). The median time to neutrophil recovery was 27 days, the median time to platelet recovery was 90 days, and the median time to erythrocyte recovery was 64 days. Among 1299 patients treated in Study 2, 77% achieved neutrophil recovery at Day 42 (75%, 79%) (95% CI) and 45% achieved platelet recovery at Day 100 (50,000/uL) (95% CI) (42%, 48%). The median time to neutrophil recovery was 25 days and the median time to platelet recovery was 122 days. Among 54 patients treated in Study 3, 91% achieved neutrophil recovery at Day 42 (81%, 97%) (95% CI) and 72% achieved platelet recovery at Day 100 (20,000/uL) (58%, 83%) (95% CI). The median time to neutrophil recovery was 22 days and the median time to platelet recovery was 50 days.

FDA Accepts Abeona Therapeutics' BLA for Epidermolysis Bullosa Gene Therapy Pz-Cel

November 14, 2024 — Abeona Therapeutics' biologics license application (BLA) for prademagene zamikeracel (pz-cel; EB-101), an investigational autologous gene-corrected epidermal sheet therapy for the treatment of patients with recessive dystrophic epidermolysis bullosa (RDEB), has been accepted for filing by the FDA.

The agency has set the Prescription Drug User Fee Act (PDUFA) action date for the BLA for April 29, 2025. Notably, the BLA is a resubmission, made by Abeona in October 2024 following a Type A meeting with the FDA that took place in August 2024 and in which the company reached an accord with the agency on necessary additional information pertaining to Chemistry Manufacturing and Controls (CMC).

“The FDA acceptance of our BLA resubmission moves us one step closer to providing pz-cel as a differentiated treatment option to address the persistent unmet needs of people with RDEB in the US,” Vish Seshadri, PhD, MBA, the chief executive officer of Abeona, said in a statement. “We look forward to continuing to work with the FDA to finalize the review of the pz-cel application.”

FDA Announces Probe Into bluebird's Elivaldogene Autotemcel for Hematologic Malignancies

November 27, 2024 — The FDA has announced it will be investigating a number of reports it has recieved on bluebird bio's approved autologous hematopoietic stem cell (HSC)-based gene therapy elivaldogene autotemcel (eli-cel; marketed as Skysona), related to incidence of hematologic malignancies. In its announcement, the agency noted that some of these cases have included life-threatening cases of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in patients with early, active cerebral adrenoleukodystrophy (CALD).

Notably, the agency mentioned that reports were received from clinical trials, with these cases diagnosed between 14 to 92 months after treatment with elivaldogene autotemcel.

"FDA is investigating the known risk of hematologic malignancies with serious outcomes, including those such as hospitalization, the requirement for allogeneic hematopoietic stem cell transplantation, and death, and is evaluating the need for further regulatory action," the agency stated. As hematologic malignancies pose a serious risk to patients, the agency is urging health care providers to carefully consider alternative treatments at this time—including allogeneic hematopoietic stem cell transplant (HCST) for patients who have a suitable, willing, and available human leukocyte antigen-matched donor—prior to deciding to move ahead with elivaldogene autotemcel.