FDA Activity Recap: January 2025 Features CRL, Multiple Clinical Holds, and More

Last month, January 2025, 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 issuing a complete response letter (CRL) to Atara Biotherapeutics regarding its biologics license application (BLA) for tabelecleucel (tab-cel, also known as Ebvallo) and placing clinical holds on several of the company's trials, clearing an investigational new drug (IND) application for ViGeneron’s retinitis pigmentosa (RP) gene therapy, and fast tracking Solid Biosciences’ Friedreich ataxia (FA) gene therapy SGT-21. 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 Issues CRL for Atara Biotherapeutics’ BLA for T-Cell Immunotherapy Tabelecleucel for EBV+ PTLD

January 16, 2025 — The FDA has issued a CRL to Atara Biotherapeutics regarding its BLA for tab-ce, also known as Ebvallo, an allogeneic Epstein-Barr virus (EBV)-specific T-cell immunotherapy, which is under evaluation for the treatment of patients with relapsed/refractory EBV-positive post-transplant lymphoproliferative disease (EBV+ PTLD).

Notably, the CRL was related to issues with a standard prelicense inspection of a third-party manufacturer for tab-cel rather than to any concerns regarding the efficacy and safety data contained within the BLA. The manufacturing process itself was not implicated, and the FDA has not requested additional clinical trials for tab-cel.

“We are working closely with our partner Pierre Fabre Laboratories, the FDA, and the third-party manufacturer to address the feedback to support marketing approval for Ebvallo,” Cokey Nguyen, PhD, the president and chief executive officer of Atara, said in a statement. “Once the third-party manufacturer GMP compliance issues have been adequately addressed, we will file for a resubmission, which we would expect to be potentially approved within 6 months of resubmission. Atara and its partner Pierre Fabre remain confident in the potential of Ebvallo and are committed to bringing this potential first-in-class medicine to United States patients with EBV+ PTLD who have limited treatment options and significant unmet need.”

All of Atara Biotherapeutics’ T-Cell Immunotherapy Trials Placed on Clinical Hold by the FDA

January 21, 2025 — The FDA has placed clinical holds on Atara Biotherapeutics’ active investigational new drug applications, which include clinical trials for tab-cel, an allogeneic EBV-specific T-cell immunotherapy under evaluation for patients with relapsed/refractory EBV+ PTLD, and ATA3219, an investigational allogeneic CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy consisting of EBV-sensitized T-cells that have not been genetically modified being evaluated for nonHodgkin lymphoma (NHL) and systemic lupus erythematosus (SLE).

Clinical trials impacted include the phase 3 ALLELE clinical trial (NCT03394365) in EBV+ PTLD for tab-cel, a phase 1 clinical trial (NCT06429800) in SLE for ATA3219, and a phase 1 clinical trial (NCT06256484) in r/r B-cell NHL for ATA3219. The hold is related to a good manufacturing practice (GMP) compliance issue identified at a third-party manufacturer for tab-cel while the FDA was conducting a prelicense inspection forth product in relation to its BLA. Although ATA3219 is produced at a separate facility that is in full compliance with GMP, starting materials used in its production come from the aforementioned third-party manufacturer and are thus implicated.

“We intend to work closely with the FDA to address these issues as expeditiously as possible,” Cokey Nguyen, PhD, the president and chief executive officer of Atara, said in a statement. “We are encouraged with ongoing correspondence with the Agency and a potential path to submitting the necessary data to release the clinical hold. Patient safety remains our priority and maintaining the highest standards for our programs.”

Allogene Therapeutics’ ALLO-329 Cleared by FDA for Phase 1 Clinical Trial in Rheumatology Indications

January 28, 2025 — Allogene Therapeutics’ ALLO-329, an investigational allogeneic CAR-T therapy, has received clearance of an IND application from the FDA for a phase 1 rheumatology basket study.

In light of the IND clearance, Allogene intends to go forward with plans for RESOLUTION, a phase 1 clinical trial (NCT identifier pending) for ALLO-329 in systemic lupus erythematosus, lupus nephritis, idiopathic inflammatory myopathies, and systemic sclerosis. The study, which Allogene anticipates will be launch in the middle of this year, will include 2 different lymphodepletion arms. In one arm patients will receive cyclophosphamide alone for lymphodepletion and in the other no lymphodepletion regimen will be used.

Notably, ALLO-329 targets both CD19+ B-cells and CD70+ activated T-cells, with the intention of eliminating dysfunctional cells of both types. Furthermore, the CAR-T product utilizes the company’s Dagger technology, which is intended to reduce or eliminate the need for lymphodepletion by making the CAR-T more resistant to rejection by the patient’s immune system. Allogene stated that ALLO-329 may be able to be manufactured at a scale of 60,000 doses annually. In addition, the potential to reduce or circumvent the need for lymphodepletion prior to treatment may allow more patients to be eligible for the product.

ViGeneron Snags FDA Rare Pediatric Disease Designation for CNGA1-Associated Retinitis Pigmentosa Gene Therapy VG901

January 14, 2025 — ViGeneron’s VG901, an investigational adeno-associated virus (AAV) vector-based gene therapy being evaluated for the treatment of RP caused by mutations in the CNGA1 gene in a phase 1b clinical trial (NCT06291935), has been granted rare pediatric disease designation (RPDD) by the FDA.

In addition to the new designation, ViGeneron also announced that the data safety monitoring board (DSMB) for the trial has given the green light for dose escalation. VG90 is intended to deliver a copy of CNGA1 to retinal photoreceptor cells via a proprietary AAV capsid referred to as vgAAV. It is administered by intravitreal injection.

“This RPDD recognition from the FDA highlights the significant unmet medical need in retinitis pigmentosa and underscores VG901’s therapeutic potential as the first-in-class and only clinical-stage therapy targeting retinitis pigmentosa associated with mutations in the CNGA1 gene,” Caroline Man Xu, PhD, ViGeneron’s cofounder and chief executive officer, said in a statement. “In addition to the previously granted FDA orphan drug designation for VG901, the RPDD designation further supports our efforts to accelerate the development of VG901.”

Solid Biosciences’ Friedreich Ataxia Gene Therapy SGT-212 Garners Fast Track Designation

January 21, 2025 — Solid Biosciences’ SGT-212, an AAV vector-based gene therapy intended to treat Friedreich ataxia (FA), has been granted fast track designation by the FDA.

SGT-212, a dual route gene transfer therapy, is intended to be delivered both by intradentate nucleus (IDN) infusion and intravenous (IV) infusion at the same time. The therapy provides a functional copy of the disease-targeted human frataxin (FXN) gene. The IDN infusion utilizes an FDA-approved stereotactic, MRI-guided device to target the cerebellar dentate nuclei, whereas the IV infusion is intended to target cardiomyocytes. The therapy is expected to treat neurologic, cardiac, and systemic clinical manifestations of the disease. Notably, the University of Pennsylvania, Solid Biosciences, and FA212 LLC, which was founded by parents of children with FA, each contributed to the development of the investigational therapeutic.

“SGT-212 is the only FA therapy in development that is designed to address frataxin deficiency, the underlying cause of FA, and all manifestations of this devastating disease, and in doing so, hopefully halt the full spectrum of symptom progression regardless of where the patient is in their journey with this terrible disease,” Bo Cumbo, BS, the president and chief executive officer of Solid Biosciences, said in a statement. “We believe fast track designation may enable us to more rapidly develop SGT-212 and bring hope to those living with FA who need and deserve better treatment options.”

Arbor Biotechnologies’ CRISPR-Based Gene Editing Therapy ABO-101 Cleared for US Trial in Primary Hyperoxaluria Type 1

January 6, 2025 — Arbor Biotechnologies’ ABO-101, a lipid nanoparticle (LNP)-delivered CRISPR-based gene editing therapy, has received clearance from the FDA for an IND application, enabling a phase 1/2 study in primary hyperoxaluria type 1 (PH1).

In light of the IND clearance, Arbor noted it has designed redePHine, a phase 1/2 clinical trial (NCT identifier pending) that will evaluate ABO-101 in adults and children with PH1. ABO-101 consists of mRNA expressing a novel Type V CRISPR Cas12i2 nuclease and a guide RNA directed at the human HAO1 gene, both of which are delivered via an LNP licensed from Acuitas Therapeutics. It is intended to inactivate HAO1 in order to decrease build up of oxalate, buildup of which is caused by enzyme deficiencies in patients with PH1.

“We are thrilled to advance ABO-101 to the clinic as we believe it has the potential to be a first-in-class treatment for PH1, a rare disease with a high unmet need, and reinforces the promise of our precisely tailored gene editing approach,” Dan Ory, MD, the chief medical officer of Arbor Biotechnologies, said in a statement. “ABO-101 is supported by a strong suite of preclinical data demonstrating specific and durable in vivo editing of HAO1 and corresponding, therapeutically relevant reductions in urinary oxalate in PH1 disease models.”