In another sign of biopharma's waning interest in the traditional ex vivo gene therapy approach, CSL Behring is shutting down its U.S. R&D hub for cell and gene therapy in Pasadena, California, Fierce Biotech has learned.
Employees were notified of the decision in July, and about 60 workers at the site are being affected, a person familiar with the process told Fierce Biotech. Some staffers already left the site in October, according to a second person.
The decision to wind down operations at the Pasadena site is part of a larger rethink around ex vivo lentiviral vector (LVV)-based gene therapies at CSL, the first person said. The Australian company’s gene therapy labs and manufacturing facilities in Marburg, Germany; Bern, Switzerland; and Sydney are also undergoing changes accordingly, the person said.
A CSL spokesperson confirmed the shutdown and the company's broader gene therapy pivot to Fierce Biotech.
“As part of our regular portfolio assessment, we have made the strategic decision to deprioritize ex vivo lentiviral-based gene therapy and to explore other gene therapy approaches,” the spokesperson said in a statement.
As CSL closes its Pasadena operations by the end of January 2025, the company will move its cell and gene therapy R&D activities to Waltham, Massachusetts, the spokesperson added. The decision was made after a strategic evaluation of CSL’s R&D footprint identified synergy opportunities between the company’s self-amplifying mRNA and lipid nanoparticle capabilities, according to the spokesperson.
“This strategic shift will enable us to focus our resources on areas showing the most promise while enabling our teams working on the leading edge of genetic medicines—such as mRNA and gene therapy—to work closely together,” the spokesperson said.
In tandem with the shift, about 30 employees will be leaving CSL, while some others have accepted offers to relocate to the Waltham site, according to the spokesperson.
CSL Behring gained the Pasadena lab and office space in 2017 as part of the acquisition of ex vivo hematopoietic stem cell gene therapy specialist Calimmune. CSL later added cell manufacturing capabilities and additional lab facilities to the site.
Last year, the company opened an R&D center in Waltham for its vaccines unit Seqirus to develop mRNA vaccines.
Meanwhile, as part of the change, CSL’s partnership with Seattle Children’s Research Institute, formed in 2020 with a focus on developing stem cell gene therapies for primary immunodeficiency diseases, has also been called off. An X-linked Agammaglobulinemia candidate, coded CSL215, has been transitioned back to Seattle Children’s, while CSL continues to look for partners for its Wiskott-Aldrich syndrome program, according to the spokesperson.
The FDA has approved several LVV-based gene therapies, but the earlier-generation technology has its share of problems, including the risk of cancer caused by insertion of the LVV into the genome.
The pivot comes as CSL works through a slower-than-expected launch of an approved gene therapy product. After an FDA approval in November 2022, CSL’s hemophilia B therapy Hemgenix only reached 12 patients during the company’s fiscal year 2024, which ended in June, CEO Paul McKenzie told investors during an earnings call in August.
“We need to continue to work across this U.S. fragmented system,” McKenzie said. “We’ve been able to increase the referrals quite significantly. But again, the U.S. healthcare system is quite fragmented, and it’s taken us longer than we had planned to penetrate that.”
The change in gene therapy R&D has no impact on Hemgenix, the CSL spokesperson told Fierce.
“Building on the success of Hemgenix, CSL continues to develop technologies to make therapeutic gene delivery more precise and durable, so that CSL can deliver on the potential of a long-term cure,” the company said in its annual report published in August.
CSL isn’t the only player that has struggled with the groundbreaking but costly therapeutic approach. After a slow start for its hemophilia A gene therapy Roctavian, BioMarin this summer decided to focus its commercial efforts on three markets—the U.S., Germany and Italy—where it has already secured reimbursement policies. The shift in Roctavian strategy was accompanied by layoffs as part of a companywide overhaul.
Pfizer, which sells Hemgenix’s gene therapy rival Beqvez, recently launched a round of layoffs at its gene therapy site in Sanford, North Carolina, following a high-profile trial failure for its Duchenne muscular dystrophy gene therapy candidate. Last year, the New York pharma also divested its preclinical gene therapy programs.
Bluebird bio, a pioneer in gene therapy known for its LVV platform, is teetering on the brink of a business crisis despite having three commercial gene therapies: Lyfgenia, Skysona and Zynteglo. In September, the Massachusetts biotech disappointed investors by narrowing its 2024 projection to about 85 patient starts, the lower end of its previous guidance. To save costs and extend its cash runway, bluebird initiated a major restructuring in September, reducing its head count by about 25%.
Bluebird is betting its future on the hope that adoption of its freshly FDA-approved sickle cell disease gene therapy, Lyfgenia, will help it break even on quarterly cash flows in the second half of 2025. Still, its current funds are only estimated to be able to support operations into the first quarter of next year.
Elsewhere, Takeda last year ended its early-stage research work on gene therapies that are based adeno-associated virus vectors. And GSK simply decided to “end our investment in cell and gene therapy,” CEO Emma Walmsley said in early 2023.
But there are companies that have doubled down on ex vivo gene therapies, suggesting the field is not dead. In the hematopoietic stem cell gene therapy space, Kyowa Kirin paid $387 million upfront to acquire Orchard Therapeutics, whose gene therapy for the rare neuromotor genetic disease metachromatic leukodystrophy, Lenmeldy, scored an FDA approval in March.
The Pfizer portfolio of preclinical gene therapy projects was bought by AstraZeneca’s rare disease unit Alexion.
Roche, while struggling to make progress with its gene therapy unit Spark Therapeutics, just expanded its gene therapy partnership with Dyno Therapeutics to design novel AAV vectors.