Janet Macpherson, Ph.D.
Director
SpanCyte Pty Ltd
Sydney, NSW, Australia
As we start 2025, many of our cell and gene therapy colleagues are heading to the first big events of the year. JPM Healthcare in San Francisco (13-16 Jan 2025) followed by Advanced Therapies Week in Dallas (20-23 Jan 2025), and for those who are not able to attend, we can follow the highlights via social media.
Before we get too caught up in looking forward to what’s next with the flurry of announcements of partnerships, mergers and acquisitions, let’s take a few moments to reflect on the advances in the field of cell and gene therapy in 2024, specifically product approvals, not just in USA but around the globe adding to approvals and patient access since 2017.
Have you ever asked if the initial products have lived up to market/clinical expectations? What is required to keep the approved products on the market and importantly for all those in product development, how do we ensure new product approvals continue?
Based in Australia, I am very aware of the need to have a larger market than Australia offers. However, in other countries where the population is larger than Australia, there might be other barriers to approval. It has been my experience that as cell therapy product developers we focus on the manufacturing process, the clinical effects in defined patient populations but we tend to lag in field of reimbursement strategy. Who is going to pay for this, and how much are they willing to pay? This is crucial to ensure patients have access to life-saving therapies around the globe.
In the USA, 7 CAR T-cell products have FDA marketing approval, and each has received marketing approval in other major healthcare markets. Unfortunately, some markets including New Zealand and emerging economies like India have not seen approval of any of these commercial products.
Seven Cell and Gene Therapy products received approval by the FDA in 2024 (Amtagvi, Aucatzyl, Beqvez, Kebilidi, Ryoncil, Symvess, Tecelra). Many of these marked ‘firsts’ in the field for USA.
On 16 February 2024, Iovance Biotherapeutics Inc lifileucel (Amtgvi) was approved under accelerated approval based on objective response rate for melanoma. After more than 30 years in development, this became the first treatment for cancer to use tumor-infiltrating lymphocytes, or TILs and the first cellular therapy to be approved for a solid tumor.
The first 2024 gene therapy approval was on 25 April. Fidanacogene elaparvovec-dzkt (Beqvez) from Pfizer, Inc was approved for the treatment of adults with moderate to severe hemophilia B (congenital factor IX deficiency). Importantly, this AAV gene therapy is only available to patients who do not have neutralizing antibodies to adeno-associated virus serotype Rh74var (AAVRh74var) capsid as detected by an FDA-approved test.
To kick of the 2nd half of 2024, afamitresgene autoleucel, or afami-cel (Tecelra), from Adaptimmune LLC was approved to treat some people with metastatic synovial sarcoma, a soft tissue sarcoma. This is the first approved T-cell receptor (TCR) therapy for cancer. This therapy is only suitable for patients with specific HLA-A2 types and whose tumor expresses the MAGE-A4 antigen as determined by an FDA-approved test.
The pace increased towards the end of 2024 with Autolus Limited receiving approval on November 8 of obecabtagene autoleucel (Aucatzyl) for the the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). This is a CD19 CAR T-cell that is given in 2 doses tailored to the patient’s leukaemia burden.
PTC Therapeutic’s eladocagene exuparvovec-tneq (Kebilidi) received accelerated approved on 13-November 2024. This is an AAV2 vector comprising a human dopa decarboxylase (DDC) for the treatment of aromatic L amino acid decarboxylase (AADC) deficiency. This therapy is administered directly to the brain by specialist surgeons using a specific device that was also approved by the FDA. This follows the earlier approval in UK and European Union in 2022 under the brand name Upstaza.
The year closed with 2 more approvals on December 19, 2024. Marking the first Mesenchymal stem cell product approval in USA, remestemcel-L-rknd (Ryoncil) was finally approved for the treatment of steroid-refractory acute graft versus host disease (SR-aGvHD) in pediatric patients 2 months of age and older. Mesoblast’s persistence in working with the FDA finally paid off adding USA to the list of countries where this product is approved.
On the same day, acellular tissue engineered vessel-tyod (Symvess) a first of its kind human derived biological vessel from Humacyte Global, Inc. received approval for use in adults as a vascular conduit for extremity arterial injury when urgent revascularization is needed to avoid imminent limb loss, and autologous vein graft is not feasible.
In Europe, Pfizer’s fidanacogene elaparvovec (Beqvez previously Durveqtix) was approved in on July 24 for treatment of severe and moderate hemophilia B. This is the same product approved by FDA in April.
Marketing authorization was issued to Vertex Pharmaceuticals for Exagamglogene autotemcel (Casgevy) on 9 February as the first gene editing therapy to treat beta thalassemia and severe sickle cell disease.
Two CAR-T therapies have received approval from the Chinese National Medical Products Administration (NMPA). JW Therapeutics Relmacabtagene autoleucel or relma-cel(Carteyva) received approval for treatment of mantle cell lymphoma. relma-cel, is autologous and targets CD19, has previously been approved by the NMPA in 2021 and 2022 respectively, for 2 other indications: adults with r/r large B-cell lymphoma (LBCL) who have previously received at least 2 lines of systemic therapy and adults with follicular lymphoma (FL) whose disease is refractory or relapsed within 24 months of second-line or later systemic treatment.
The late 2023 approval of another domestic CD19-targeting CAR-T therapy inaticabtagene autoleucel (Yuanruida), from CASI Pharmaceuticals and Juventas Cell Therapy was the first approved for relapsed/refractory B-Cell Acute Lymphocytic Leukemia.
Continuing the approval of domestic CD19 CAR-T products, we saw 2 products receive approval from the Indian Central Drugs Standard Control Organisation (CDSCO). In October 2023 ImmunoACT’s actalycabtagene autoleucel (NexCAR19) became the first product for B-Cell Acute Lymphoblasitc Leukemia or B-cell lymphoma or leukemia based on clinical data from the TATA Memorial Centre in Bombay. More recently in May 2024, Immuneel based in Bengaluru received approval for varnimcabtagene autoleucel, var-cel (Qartemi) for use in treatment of relapsed and refractory Non Hodgkin’s Lymphoma (NHL). This product is also approved in Spain for delivery at Hospital Clinic Barcelona.
2024 was one for the record books with so many ‘first’ approvals. However, I have no doubt that 2025 will bring even more from our outstanding ISCT members and the Cell and Gene Therapy industry more widely. I am looking forward to seeing how much difference we can make to patient lives.
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