From the Editor: Cell and Gene Therapy - Marketing Approvals to Advance Patient Outcomes

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Janet Macpherson, PhD
Cytiva
Sydney, Australia

Your Telegraft editorial team are dedicating this first issue of 2024 to a reflection of 2023 content and highlights. Please do take the opportunity to catch up on articles that you may have missed during the busy year that was 2023.

On the Cell Therapy front (including genetically modified and gene engineered cells, the year kicked off on Jan 4^thwith the UK approvals of Johnson & Johnson’s BCMA CAR-T therapy ciltacabtagene autoleucel (Carvykti) for both relapsed and refractory Multiple Myeloma under an Orphan Drug Designation. This was followed in April with the FDA approval of Gamida Cell Inc’s omidubicel (Omisirge) for Hematopoietic Stem Cell Transplantation. Omidubicel is a single intravenous infusion of patient-specific human allogeneic cord blood-derived stem cells processed and cultured with nicotinomide. The following month, Atara Biotherapeutics Inc’s tabelecleucel (Ebvallo) was approved by the FDA under orphan designation for both Post-Transplant Lymphoproliferative Disorder and Epstein–Barr Virus (HHV-4) Infections. In June equecabtagene autoleucel (Fucaso) from Nanjing IASO Biotherapeutics Co Ltd received approval in China under China National Product Administration (NMPA) for Relapsed Multiple Myeloma, making it the world’s first commercially available fully human CAR-T therapy.

Perhaps a slow starter but they made it: donislecel-jujn (Lantidra) from CellTrans Inc was approved by the FDA at the close of the first half of the year, after receiving orphan designation in 2017. It was approved for the treatment of Type 1 Diabetes (Juvenile Diabetes) in patients unable to achieve target HbA1c (poor control).

The second half of the year was good news for patients with haemoglobinopathies! In November we received news of the UK approval of Vertex Pharmaceuticals (Europe) Ltd’s exagamglogene autotemcel (Casgevy) for both Beta Thalassaemia and Sickle Cell Disease with Vaso-Occlusive Crisis, and in December FDA approval for the Sickle Cell Disease with Vaso-Occlusive Crisis indication.

Bluebird bio was successful in gaining FDA marketing approval in December for lovotibeglogene autotemcel (Lyfgenia) for Sickle Cell Disease with Vaso-Occlusive Crisis following expedited designations including Rare Pediatric Disease Designation.

Also in 2023 was the marketing approval of actalycabtagene autoleucel from ImmunoAct Pvt Ltd, who received marketing authorization for B-Cell Acute Lymphocytic Leukemia (B-Cell Acute Lymphoblastic Leukaemia) in India. This marks the first CAR T-cell marketing approval in India.

On May 19, 2023, the FDA approved beremagene geperpavec (Vyjuvek) as the first topical gene therapy. Krystal Biotech, Inc’s Vyjuvek was approved for the treatment of wounds in patients with dystrophic epidermolysis bullosa (DEB), a rare and serious disease that affects the skin and mucosal tissues caused by mutations in the COL7A1 gene. In another first, it is the first re-dosable gene therapy. Then on June 22, 2023, the FDA approved the first gene therapy treatment for Duchenne Muscular Dystrophy (DMD), ElevidysTM (delandistrogene moxeparvovec-rokl), from Sarepta Therapeutics as a one-time treatment for pediatric patients in a narrow age window of 4-5 years with confirmed mutation in the DMD gene. The approval label was restricted in part due to the clinical manifestations of disease in older patients, and partly due to changes in the manufacturing process during clinical development.

Later in the year, the FDA approved the first gene therapy treatment for adults with severe hemophilia A, Roctavian, from BioMarin. The one-time, single-dose infusion was first approved by the EMA in 2022.

Two of the most significant gene therapy approvals came on the same day, Dec. 8, and for the same indication, sickle cell disease. They are both cell delivered gene therapies. Vertex and CRISPR was approved for Casgevy, the first drug to reach the market that was developed with CRISPR gene editing technology and bluebird bio for Lyfgenia.

Gene therapy treatments based on genetic engineering, provide a radical new paradigm for treatment of diseases due to gene mutations. They address the underlying genetic cause of diseases and could transform the quality of life for patients that previously had no hope of clinical improvement. Now gene therapies and gene editing technologies are being developed for treatment of autoimmune diseases, cancer, and infectious diseases. The possibilities are broad and exciting.

On the other hand, we did see a few discontinuations; including Debamestrocel from BrainStorm Cell Therapeutics Inc, for Amyotrophic Lateral Sclerosis, and others like the demise of Tessa Therapeutics. While this is not what we want to see, the typical molecule development pipeline would predict many more products failing in clinical development than we have observed to date.

2023 was a big year of approvals, especially compared to the low seen in 2022. So what might we see in 2024? The number and scope of filings for accelerated approvals is not slowing or narrowing. With the continued upskilling of our workforce from discovery through to commercialisation and marketing, I predict 2014 will be a bumper year – bring it on!!!.

Table 1. In 2023 the FDA Center for Biologic Evaluation and Research approved cell and gene therapies including the first CRISPR–Cas9-based gene editing product, and others for rare diseases. (After Ref 1)