Cell and gene therapy sector reaches milestones in 2024, challenges remain
2024 was a “transformative year marked by groundbreaking milestones and continued maturation” for the cell and gene therapy sector, according to a year in review from the Alliance for Regenerative Medicine (ARM).
“From pivotal breakthroughs to regulatory firsts, the sector is setting the stage to redefine clinical and commercial success,” ARM said, noting that this year saw a record number of approvals in the U.S.
In oncology, ARM highlighted the fact that “solid tumors have been more challenging targets for the sector than blood cancers.” However, 2024 saw critical breakthroughs with the first-ever approvals of two different adoptive cell therapies for treating solid tumors, including Iovance Biotherapeutics’ FDA approval for its tumor infiltrating lymphocyte therapy to treat metastatic melanoma, and Adaptimmune Therapeutics’ FDA approval for its T-cell receptor therapy to treat synovial sarcoma.
Breakthroughs, such as gene therapies, are similarly reaching more patients. “At the end of 2024, patients with hemophilia B and patients with transfusion-dependent thalassemia in the U.S. and EU also have two options to choose from,” according to ARM.
At the same time, ARM commented that until this year, two CAR-T cell therapies for multiple myeloma could only be used in the U.S. and EU as the last lines of treatment for blood cancer patients who had exhausted all other options.
However, Abecma — a CAR-T therapy developed by Bristol Myers Squibb and 2seventybio — “was approved as a third-line treatment in the U.S. and EU after previously being a fifth-line treatment in both regions,” ARM said. “Carvykti, another CAR-T developed by Legend Biotech and Janssen, was approved as a second-line treatment in the U.S. and EU after being a fifth-line treatment in the U.S. and a fourth line treatment in the EU.”
While this year’s milestones for the sector were noteworthy and expectations are high for the clinical pipeline in 2025, challenges remain next year for cell and gene therapy manufacturing.
Challenges for bluebird bio
Andrew Obenshain, CEO of bluebird bio, in January emphasized the importance of manufacturing at ARM’s annual Cell & Gene State of the Industry Briefing in San Francisco.
Cell and gene therapy companies “are essentially manufacturing companies,” according to Obenshain, who said that “unlike other therapeutic companies ... you really have to invest in your manufacturing capabilities, capacity and expertise — and not in the traditional areas necessarily where you would’ve in a biotech company or pharma company.”
Obenshain said that cell and gene therapy companies must prioritize manufacturing “first” in addition to their clinical and research teams “and then everything else really has to take a back seat to that as you go forward.”
However, bluebird in September announced that it was laying off about 25% of its employees — more than half of whom work in R&D — as part of a restructuring aimed at reducing cash operating expenses.
The gene therapy company reported $118.7 million in cash and cash equivalents on hand as of September 30, which will only last into the first quarter of 2025. In November, bluebird reported third-quarter 2024 revenue of $10.6 million, down from $16.1 million in the previous quarter.
CFO James Sterling in an analyst call last month blamed “variation in manufacturing timelines” for the drop in Q3 revenue, while Obenshain said bluebird took steps in the quarter to increase manufacturing capacity for its ex vivo gene therapy Zynteglo for the rare blood disorder beta-thalassemia.
Despite securing FDA approvals for three therapies in under two years, including Lyfgenia, Skysona and Zynteglo, bluebird continues to struggle financially.
Tom Klima, bluebird’s chief commercial and operating officer, told analysts last month that the company has the manufacturing capacity it needs “to achieve our cash flow breakeven point” in the second half of 2025, with plans to double capacity in 2026 for its cell-based gene therapy Lyfgenia for the treatment of patients with sickle cell disease.
Klima noted that bluebird in 2024 expanded its capacity at contract development and manufacturing organization Lonza for Zynteglo and gene therapy Skysona, which is used to treat children with cerebral adrenoleukodystrophy.
While bluebird is seeing variability in manufacturing timelines, 70 to 90 days for Zynteglo and 90 to 105 days for Lyfgenia, Obenshain told analysts that “in general, we’ve been very pleased with the quality of our manufacturing, the timeliness.”