After raising a record $19.9 billion in funding in 2020, doubling the previous year, the cell and gene therapy industry shows no signs of slowing down. Forecasters predict more record growth this year, especially in terms of regulatory decisions; at least nine new products have been approved or are up for approval in the United States and Europe.
Michael Lehmicke, Senior Director, Science and Industry Affairs at the Alliance for Regenerative Medicine, says 2021 is still set to be another big year for a burgeoning industry. That’s despite the ongoing challenges presented by COVID-19—such as supply chain disruptions and reduced manufacturing capacity.
“We’ve seen some significant scientific milestones … in areas including iPSCs, gene editing and allogeneic cell-based immunotherapies,” Lehmicke noted recently. “The regenerative medicine pipeline continues to expand.”
Fueling this growth are green lights on the road to product commercialization. Of the recent and expected regulatory actions:
- Five are for chimeric antigen receptor T-cell (CAR-T) therapies that target lymphomas and multiple myeloma
- Three are designed to treat genetic disorders
- One (StrataGraft) is being developed for the treatment of severe burns
Trials are also underway for cell therapies that target indications with larger patient pools—from diabetes to cardiovascular disease.
CAR-Ts come of age
March was a particularly busy month for CAR-T therapy approvals. Coming on the heels of FDA authorization in February, Japanese regulators in March approved Bristol Myers Squibb’s CAR-T therapy Breyanzi for the treatment of relapsed or refractory (R/R) large B-cell lymphoma and R/R follicular lymphoma. Approvals were based on data from the TRANSCEND NHL 001 trial, in which 73% of patients tested achieved a positive response. The European Medicines Agency (EMA) is also reviewing Breyanzi for approval.
Meghan Gutierrez, Chief Executive Officer, Lymphoma Research Foundation, says patients battling these diseases “face a challenging treatment journey, both physically and emotionally.” She says Breyanzi is one reason “for this community to maintain hope for the future.”
Also in March, the FDA approved a second Bristol Myers Squibb CAR-T treatment, Ide-cel. Ide-cell is the industry’s first CAR-T medicine approved for treating patients with multiple myeloma. Co-developed with bluebird bio Inc., Ide-cel was first earmarked for review in Europe two years ago after validation of the company’s marketing authorization application.
On March 5, Santa Monica-based Kite pharma received FDA approval for its CAR-T treatment, Yescarta, for patients with R/R follicular lymphoma. Yescarta was approved for similar use in Japan in January.
In October 2017, Yescarta became the first CAR-T therapy to be approved by the FDA for the treatment of adult patients with R/R large B-cell lymphoma after two or more lines of systemic therapy. The CIBMTR® (Center for International Blood and Marrow Transplant Research®), a research collaboration between the National Marrow Donor Program®/Be The Match® and the Medical College of Wisconsin, is working with Kite to track long-term outcomes of patients treated with Yescarta.
Other rare blood cancer CAR-T treatments nearing the regulatory finish line include Janssen’s Cilta-cel and JW Therapeutics’ JWCAR029. Both are up for review later this year.
A diverse pipeline
In addition to the CAR-T pipeline, a number of gene therapies targeting rare genetic disorders are inching closer to commercialization. One is bluebird’s eli-cel. Eli-cel is a one-time ex vivo treatment for cerebral adrenoleukodystrophy, a rare X chromosome-linked disorder.
Long-term data shows that the gene therapy, which produces a functional copy of the mutated gene, ABCD1, is highly effective at stabilizing disease progression. In March, the company reported that 90% of patients in a Phase 2/3 trial were alive and free of major functional disabilities two years after dosing. Bluebird is preparing to seek FDA approval this summer. The EMA accepted an application for approval of eli-cel in October.
Another gene therapy to watch is PTC-AADC from PTC Therapeutics. The therapy targets AADC deficiency, a rare mutation in the DDC gene that affects the central nervous system. PTC-AADC is currently under review for approval in Europe. A Biologics License Application (BLA) is expected to be filed with the FDA in the second quarter of this year.
Meanwhile, GenSight Biologics is expecting an FDA decision for its gene therapy treatment Lumevoq. The gene therapy targets Leber’s hereditary optic neuropathy, a maternally inherited mitochondrial disease. GenSight filed for use in Europe in September 2020.
Finally, StrataGraft from Mallinckrodt is an allogeneic skin tissue therapy for the treatment of severe burns and other complex skin defects. Created with spontaneously immortalized human keratinocyte cells, StrataGraft’s developers say it has the potential to minimize or eliminate the need for autografting. The FDA is currently reviewing the therapy’s BLA.
The road ahead
Ongoing challenges from COVID-19 continue to have ripple effects on the cell and gene therapy industry. Despite the early flurry of regulatory activity in the first quarter of the year, pandemic-related inspection delays have slowed decisions in recent months.
For instance, the FDA’s action on StrataGraft, planned for February, was delayed due to travel restrictions. Supply chain disruptions will also continue to impact the sector. As trials transition into commercialized products, the scale-up of complex manufacturing processes will require innovative thinking.
Still, the months and years ahead are already looking bright. While recent product approvals have been primarily for small patient groups, the trials pipeline is full of therapies for more common diseases, such as stroke and muscular dystrophies. Within four years, the FDA expects to see 10-20 new cell and gene therapies reach the market annually.
“All indications are that 2021 will be a fantastic year in science, technology and clinical progress in this sector,” says Janet Lambert, CEO, Alliance for Regenerative Medicine. If the first four months are anything to go by, odds are Lambert’s prediction will be prescient.
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