FDA approvals for cell and gene therapies stay on track

While 2023 was heralded as a breakthrough year for cell and gene therapy with the U.S. FDA greenlighting seven new treatments, 2024 is keeping pace.

The tally currently stands at seven new approvals, plus three therapies gaining the regulator’s nod in new indications.* Importantly, the approvals span several different therapeutic areas, including hemophilia B, beta thalassemia, solid tumor cancer and fatal pediatric rare diseases.

CBER, under the direction of Dr. Peter Marks, has vowed to better leverage its accelerated approval pathway to expedite the approval of cell and gene therapies for life-threatening conditions. “We want to get more things over the finish line; this is a way to do it," said Marks during a state of the industry briefing earlier this year. Keeping to its promise, half of this year’s new CGTs were approved through the agency’s accelerated pathway.

Here's a rundown of 2024 FDA approvals:

Approvals

Amtagvi (lifileucel) — Iovance Biotherapeutics

Approval date: February 16, 2024
Indication: Unresectable/metastatic melanoma after anti-PD-1 and targeted therapy
Type: Tumor-derived autologous T cell immunotherapy

When the FDA granted accelerated approval to Iovance’s Amtagvi, it became the first one-time T cell therapy for a solid tumor cancer and the first treatment option for adults with advanced melanoma after anti-PD-1 and targeted therapy.

The proposed mechanism for Amtagvi offers a new cell therapy approach that deploys patient-specific T cells called TIL cells. When cancer is detected, the immune system creates TIL cells to locate, attack and destroy cancer. When cancer prevails, the body’s natural TIL cells can no longer perform their intended function to fight cancer. Amtagvi is manufactured using a proprietary process to collect and expand a patient’s unique T cells from a portion of their tumor. The treatment, delivered as an intravenous infusion, returns billions of the patient’s T cells back to the body to fight their cancer.

Lenmeldy (atidarsagene autotemcel) — Orchard Therapeutics 

Approval date: March 18, 2024
Indication: Early-onset metachromatic leukodystrophy
Type: Autologous ex vivo hematopoietic stem cell-based gene therapy

Orchard Therapeutics' Lenmeldy was approved for children with pre-symptomatic late infantile, pre-symptomatic early juvenile or early symptomatic early juvenile MLD — all of which previously had no treatment options beyond supportive and end-of-life care.

Lenmeldy aims to correct the underlying genetic cause of MLD by inserting one or more functional copies of the human ARSA gene ex vivo into the genome of a patient’s own hematopoietic stem cells (HSCs) using a lentiviral vector. The genetically repaired cells are infused back into the patient, where, once engrafted, they differentiate into multiple cell types, some of which migrate across the blood-brain barrier into the central nervous system and express the functional enzyme. This approach has the potential to restore enzymatic function to stop or slow disease progression with a single treatment.

Beqvez (fidanacogene elaparvovec) — Pfizer 

Approval date: April 26, 2024
Indication: Hemophilia B
Type: In vivo AAV-based gene therapy

Pfizer’s Beqvez was approved for the treatment of adults with moderate to severe hemophilia B who currently use factor IX (FIX) prophylaxis therapy, or have a history of life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes, and do not have neutralizing antibodies to adeno-associated virus serotype Rh74var (AAVRh74var) capsid as detected by an FDA-approved test.

Beqvez is an adeno-associated virus-based gene therapy designed to introduce in the transduced cells a functional copy of the FIX gene encoding a high-activity FIX variant. The one-time treatment is designed to enable people living with hemophilia B to produce FIX themselves rather than the current standard of care, which requires regular intravenous infusions of FIX that are often administered multiple times a week or multiple times a month.

Tecelra (afamitresgene autoleucel) — Adaptimmune Therapeutics

Approval date:  August 1, 2024
Indication: MAGE-A4+synovial sarcoma
Type: Genetically modified autologous T cell immunotherapy

Adaptimmune Therapeutics’ Tecelra was granted accelerated approval for the treatment of advanced MAGE-A4+synovial sarcoma in adults with certain HLA types who have received prior chemotherapy, marking the first new treatment for synovial sarcoma — a rare cancer that develops in soft tissues — in over a decade.

Tecelra is a melanoma-associated antigen A4 (MAGE-A4)-directed genetically modified autologous T cell immunotherapy which uses each patient’s own immune cells to recognize and attack their cancer cells in a one-time infusion treatment. It is thefirst engineered cell therapy for a solid tumor cancer approved in the U.S.

Aucatzyl (obecabtagene autoleucel) — Autolus Therapeutics

Approval date:  November 8, 2024
Indication:  Acute lymphoblastic leukemia
Type:  Genetically modified autologous T cell immunotherapy

Autolus’ Aucatzyl was approved for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (r/r B-ALL). The milestone approval, which marks Autolus' first commercial product, offers new hope for patients with this aggressive cancer once they relapse.

Aucatzyl is a B-lymphocyte antigen CD19 (CD19) chimeric antigen receptor (CAR) T cell therapy designed to overcome the limitations in clinical activity and safety compared to current CD19 CAR-T cell therapies. The treatment is designed with a fast target binding off-rate to minimize excessive activation of the programmed T cells. 

Aucatzyl is to be administered as split dose infusion on day 1 and day 10 (±2 days) based on bone marrow blast assessment and preceded by fludarabine and cyclophosphamide lymphodepleting chemotherapy. 

Kebilidi (eladocagene exuparvovec-tneq) — PTC Therapeutics

Approval date: November 13, 2024
Indication: AADC deficiency
Type: In vivo rAAV2 based gene therapy

PTC Therapeutics was granted accelerated approval of its gene replacement therapy for the treatment of AADC deficiency, marking the first-ever gene therapy approved in the U.S. that is directly administered to the brain.

Branded Kebilidi, the therapy is indicated for the treatment of children and adults with AADC deficiency — a rare, severe, genetic neurometabolic disorder — including the full spectrum of disease severity.  The therapy has been approved in the UK and EU since 2022 under the brand name Upstaza.

AADC deficiency is a highly morbid, life-shortening disorder that results in the inability to synthesize dopamine, a neurotransmitter essential for motor function. Kebilidi, an rAAV2-based gene therapy, is directly administered to the putamen of the brain through a stereotactic neurosurgical procedure. It is designed to correct the underlying genetic defect by delivering a functioning DDC gene directly into the putamen, increasing the AADC enzyme and restoring dopamine production. 

Kebilidi is authorized to be administered using Clearpoint Neuro’s SmartFlow Neuro Cannula, a device that can bypass the blood brain barrier and deliver therapeutics to regions of interest using convection enhanced delivery under direct image guidance.

Ryoncil (remestemcel-L) — Mesoblast Limited

Approval date: December 18, 2024
Indication: Pediatric steroid-refractory acute graft versus host disease
Type: Allogeneic human mesenchymal stem cell therapy

Mesoblast got the green light ahead of its planned January PDUFA date for remestemcel-L, branded Ryoncil, marking the first mesenchymal stromal cell (MSC) therapy approval in the U.S. The allogeneic bone marrow-derived MSC therapy, is approved for steroid-refractory acute graft versus host disease (SR-aGvHD) in children 2 months and older, including adolescents and teenagers. Ryoncil is administered via intravenous infusion given twice per week for four consecutive weeks.

Ryoncil, administered via intravenous infusion given twice per week for four consecutive weeks, is the first allogenic cellular medicine in the U.S. for SR-aGVHD, a complication that can occur in patients who receive an allogeneic bone marrow transplant.

In August 2023, the FDA handed Mesoblast a complete response letter for remestemcel-L for the treatment of pediatric SR-aGVHD, asking for more data to support marketing approval. Mesoblast agreed to conduct a targeted, controlled study in the highest-risk adults with the greatest mortality. Mesoblast refiled, and in July 2024, the FDA accepted the BLA.

Expanded indications

Casgevy (exa-cel) — Vertex, CRISPR Therapeutics

Decision date: January 16, 2024
New indication: Beta thalassemia
Type: CRISPR/Cas9 genome-edited cell therapy

Casgevy, co-developed by Vertex Pharmaceuticals and CRISPR Therapeutics, was approved for the treatment of transfusion-dependent beta thalassemia in patients 12 years and older.

The nod for TDT, a rare blood disorder that leads to chronic anemia, came ahead of the PDUFA target action date of March 30, 2024. The new indication follows Casgevy’s initial approval on December 8, 2023, when the treatment became the first gene-edited cell therapy for patients with sickle cell disease.

Breyanzi (liso-cel) — Bristol Myers Squibb

Decision date: May 30, 2024
New indication: Relapsed/refractory mantle cell lymphoma
Type: Genetically modified autologous T cell immunotherapy

Bristol Myers Squibb’s Breyanzi was approved for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least two prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor. The CAR-T cell therapy’s new approval marks the fourth distinct subtype of non-Hodgkin lymphoma for which Breyanzi is approved.

Elevidys (delandistrogene moxeparvovec-rokl) — Sarepta Therapeutics

Decision date: June 20, 2024
New indication: Duchenne muscular dystrophy for non-ambulatory individuals
Type: In vivo AAV-based gene therapy

The FDA expanded the approval of Elevidys to include the treatment of Duchenne muscular dystrophy for ambulatory and non-ambulatory individuals 4 years of age and older with DMD with a confirmed mutation in the DMD gene.

Elevidys had won accelerated approval in June 2023 for a segment of pediatric patients with DMD — specifically, ambulatory pediatric patients aged 4-5 years who have a confirmed mutation in the DMD gene. The most recent action grants traditional approval for ambulatory patients and accelerated approval for non-ambulatory patients.

Decisions to watch

revakinagene taroretcel — Neurotech Pharmaceuticals

PDUFA date: March 18, 2025
Intended indication: Macular telangiectasia type 2
Type: Allogenic encapsulated cell therapy

On November 8, Neurotech revealed that the FDA extended the PDUFA date for NT-501 by three months to allow time required for the agency to review additional data provided by the Company at the FDA’s request. The original PDUFA date of December 17 was pushed to March 18, 2025.

The treatment uses an investigational implant to leverage encapsulated cell therapy to slow the progression of macular telangiectasia type 2 (MacTel), a neurogenerative retinal disease that causes central vision deterioration.

prademagene zamikeracel (pz-cel) — Abeona Therapeutics

PDUFA date: April 29, 2025
Intended indication: Recessive dystrophic epidermolysis bullosa
Type: Autologous engineered cell therapy

In April 2024, the FDA handed Abeona a complete response letter for pz-cel for the treatment of patients with recessive dystrophic epidermolysis bullosa, citing  the need for additional CMC data. On November 12, 2024,  Abeona announced that the FDA accepted the BLA for pz-cel and set a PDUFA target action date of April 29, 2025.

Treatment with pz-cel for the rare and painful skin disorder involves using gene transfer to deliver COL7A1 genes into a patient’s own skin cells and transplanting them back to the patient to enable normal Type VII collagen expression and skin function. 

*List was updated on 12/23/24 to include the approve of Mesoblast's Ryoncil which was approved ahead of its planned PDUFA date.