The Gene & Cell Therapy Landscape: Recent Approvals and Upcoming Therapeutics of Interest

Here we take a glance at the recent advancements in therapy approvals and clinical developments across various disease areas, highlighting recent advancements in gene, cell, and RNA therapies, along with breakthroughs in hematology, neurodegenerative disorders, genetic diseases, and blood disorders. 

Current Advancements in Therapy Approvals and Clinical Development

Globally, there are currently a diverse range of approved gene, cell, and RNA therapies in clinical use. This includes 32 approved gene therapies, which encompass genetically modified cell therapies. Three notable approvals in Q1 2024 include China’s approval of CT-053 (CARsgen) for myeloma, Canada’s approval of Beqvez by Pfizer for hemophilia B, and an autologous cell therapy for melanoma in the U.S. Additionally, 28 RNA therapeutics and 68 non-genetically modified cell therapies have received regulatory approval. 

Specifically, Zevorcabtagene autoleucel (Zevor-cel or CT-053) is a fully human, autologous B-cell maturation antigen (BCMA) CAR T-cell therapy for treating relapsed or refractory multiple myeloma (R/R MM). It gained approval from the National Medical Products Administration (NMPA) on February 23, 2024, for adult patients who have previously progressed after at least three lines of therapy, including a proteasome inhibitor and an immunomodulator. 

Then, Health Canada approved Pfizer’s BEQVEZ (fidanacogene elaparvovec-dzkt) for adults with moderate to severe hemophilia B, based on findings from the Phase 3 BENEGENE-2 study, an open-label, single-arm trial. On April 26th this year, FDA approval was granted, solidifying BEQVEZ as a one-time treatment enabling patients to produce their own FIX, eliminating the need for frequent intravenous infusions typically required several times weekly or monthly.

Lastly, Amtagvi, an autologous cell therapy developed by Iovance Biotherapeutics, was approved in the U.S. on February 26th for the treatment of unresectable or metastatic melanoma under the accelerated approval pathway. As the first FDA-approved tumor-derived T cell immunotherapy of its kind, Amtagvi is indicated for the treatment of adult patients with unresectable or metastatic melanoma previously treated with other therapies, including a PD-1 blocking antibody and, if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. It works by utilizing the patient’s own T cells, extracted from a portion of their tumor tissue, which are then manufactured and infused back into the patient as a single dose. 

Recent Breakthroughs in Hematology, Neurodegenerative Disorders, Genetic Diseases, and Blood Disorders

Bristol Myers Squibb’s (BMS) Breyanzi received FDA approval on March 14 as the first CAR T cell therapy for relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia. In the pivotal TRANSCEND 004 trial, Breyanzi demonstrated a complete response in 20% of recipients, with responses lasting over 35 months, a remarkable feat in this patient population, as stated by Rosanna Ricafort, vice president and head of late development hematology and cell therapy at BMS.

Orchard Therapeutics’ Lenmeldy secured FDA approval as the first gene therapy for metachromatic leukodystrophy (MLD) in April. This rare, degenerative disease, caused by a deficiency in the arylsulfatase-A (ARSA) gene, now has a treatment option in Lenmeldy, a single-dose infusion derived from the patient’s own genetically modified hematopoietic stem cells. Lenmeldy‘s approval marks another breakthrough in gene therapy, joining the ranks of treatments for pediatric diseases such as Duchenne muscular dystrophy and cerebral adrenoleukodystrophy. Its availability offers hope to MLD patients who previously lacked treatment beyond supportive care.

Vertex and CRISPR Therapeutics’ Casgevy received FDA approval in December as the first CRISPR-based gene editing therapy for sickle-cell disease (SCD), followed shortly by approval for transfusion-dependent beta thalassemia. Despite the rapid progress in CRISPR technology, concerns remain regarding potential side effects such as cell toxicity and genomic instability.  Similarly, Bluebird bio’s Lyfgenia gained FDA approval for SCD in December, offering another promising option for patients. With its potential advantages including longer durability of data and efficacy in stroke patients, Lyfgenia presents a significant addition to the treatment landscape for SCD. 

Sarepta’s Elevidys, approved by the FDA in 2023 as the first gene therapy for Duchenne muscular dystrophy (DMD), sparked momentum in the DMD treatment landscape despite subsequent trial setbacks. The approval of Elevidys and other treatments like Agamree and Duvyzat signifies progress in addressing this debilitating disease. 

In the Pipeline: Kresladi and Breyanzi’s Therapeutic Expansions

Rocket Pharmaceuticals’ Kresladi awaits FDA decision for the rare disease leukocyte adhesion deficiency-I, with expectations set for June 30, 2024. Meanwhile, BMS anticipates FDA decisions for Breyanzi’s potential use in relapsed or refractory follicular lymphoma and mantle cell lymphoma, further expanding its therapeutic reach. 

This year’s ASGCT promises to provide invaluable insights into the rapidly evolving landscape of cell and gene therapy. With recent approvals spanning various disease areas, including CAR T cell therapy for leukemia and gene therapy for rare genetic disorders, the field has witnessed remarkable progress. 

Author

Bernice Lottering